The Male Hypogonadism Market report embarks with industry overview which interprets value chain structure, industrial environment along with regional analysis, application, market size, and forecast. It provides overall Analysis of Male Hypogonadism Market industry structure, types, applications, regions, competitors and forecast period from 2020-2026. It also determines investment opportunities and probable threats in the industry based on an intelligent analysis. Moreover, the report serves an inclusive analysis of this market by volume and value.

This report focuses on the Global Male Hypogonadism Market trends, future forecast, growth opportunity, key market and key players. The study objectives are to present the Male Hypogonadism development in North America, Europe, China, Japan, Southeast Asia, India and Central & South America.

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Topmost List manufacturers/ Key player/ Economy by Business Leaders Leading Players of Male Hypogonadism Market Are:Astrazeneca Plc.Merck& Co. Inc.Laboratories GenevrierAllergan Plc.Endo International Plc.FerringAnd More

In market segmentation by types of Male Hypogonadism, the report covers:Testosterone Replacement TherapyGonadotropin-Releasing Hormones Therapy

In market segmentation by applications of the Male Hypogonadism, the report covers the following uses:Kallmann SyndromeKlinefelters SyndromePituitary DisordersOthers

Scope of the Male Hypogonadism Market Report:

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Male Hypogonadism Market Segment by Regions, regional analysis covers:North America (USA, Canada, and Mexico)Europe (Germany, France, UK, Russia, and Italy)Asia-Pacific -(China, Japan, Korea, India, and Southeast Asia)South America (Brazil, Argentina, Columbia etc.)The Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria, and South Africa).

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Male Hypogonadism Market Historic Data (2015-2019):

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Male Hypogonadism Market Forecast (2020-2026):

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Global Male Hypogonadism Market Size |Incredible Possibilities and Growth Analysis and Forecast To 2026 | Astrazeneca Plc., Merck& Co. Inc.,...

Recommendation and review posted by Bethany Smith

How high altitudes affect peoples breathing and its coordination with the heart beat is due to genetic differences, say researchers.

Clear physiological differences have already been demonstrated between people living in the Himalayas and Andes compared with people living at sea level, revealing an evolutionary adaptation in the control of blood flow and oxygen delivery to the brain and the rest of the body.

Now an international team led by Aneta Stefanovska, PhD, a professor at Lancaster University has identified genes that are related to cardiorespiratory function during so-called acute periodic breathing. Their report is published in the Journal of Physiology.

Periodic breathing (PB) occurs in most humans at high altitudes and is characterized by periodic alternations between hyperventilation (too-fast breathing) and apnea (no breathing). The altered respiratory pattern due to periodic breathing is accompanied by changes in heart rate and blood flow.

Breathing, ECG of the heart, and microvascular blood flow were simultaneously monitored for 30 minutes in 22 healthy male subjects, with the same measurements repeated under normal and low oxygen levels, both at real and simulated altitudes of up to 3800m.

As part of the experiment, the participants were also taken in a cable car to a high altitude laboratory at the top of Aiguille du Midi mountain in Chamonix in France and tested immediately on arrival and after six hours at this altitude of 3842m.

The researchers found that orchestration between the participants hearts and lungs, as measured by phase coherence, responded differently to periodic breathing depending on whether they had one of two specific genetic variants affecting the cardiorespiratory response to insufficient oxygen.

Chronic periodic breathing is generally seen as an unfavorable state, being associated with increased mortality in chronic heart failure, but in healthy people it may be an indication of better alertness to oxygen insufficiency at high altitudes.

Hypoxia, as well occurring during rapid ascents to high-altitudes, can also be a significant problem at sea-level, being a contributory factor in many health conditions including cancer, strokes, and heart attacks.

Stefanovska says in a release, The similarities between hypoxia-induced PB at altitude, and the breathing characteristics observed in certain pathological states, provide an opportunity to further our understanding of the physiological processes involved in chronic hypoxic states that occur even when oxygen is abundant.

Considering living systems as collections of interacting oscillators whose dynamics is governed by multiple underlying open systems enables the observation of functional changes over time, and investigation of how they are altered in health and disease.

Image: Participants were also taken in a cable car to a high altitude laboratory at the top of Aiguille du Midi mountain in Chamonix in France. Credit: Lancaster University

Originally posted here:
How Cardiorespiratory Function Is Related to Genetics - Sleep Review

Recommendation and review posted by Bethany Smith

It is a truth universally acknowledged that cancer prevention and early cancer detection saves lives.

As scientists and physicians at the major cancer centers work together to unravel the link betweengenetic alterations and cancer risk, genetic testing is rapidly becoming an impactful tool for matching patients to individualized cancer screening programs.

Often called the Angelina Jolie effect based on the actor'slaudable effort to enhance understanding of increased cancer risk for patients with alterations in the BRCA1 or BRCA2 genes the general public has become appropriately more aware of the importance that genetics can play in cancer risk.

Put most simply, genetic testing utilizes DNA usually obtained from small amounts of saliva or blood to identify a genetic mutation, or change, in your DNA that may increase your risk of developing certain cancers. This is determined by sequencing the DNA, which reads the specific DNA code for a subset of genes known to be important for affecting cancer development.

Individuals with a strong family history of cancer or those of a certain ancestry, such as Ashkenazi Jewish ancestry, might be more likely to carry these genetic mutations, but lack of a family cancer history does not mean that someone wont be a carrier. In many cases, genetic risk of cancer arises spontaneously through DNA errors that occur in developing embryos. In other words, genetic risk can result from a spot of ill-timed bad luck, on or before your journey began at the single cell stage.

Being aware that you have a genetic mutation that might increase your risk of developing cancer can help you and your doctor work together and create a personalized plan to help increase your chance of prevention or early detection.

For a man carrying specific alterations in the BRCA2 gene, there may be concern for increased risk of prostate or pancreatic cancer development. The team approach is then taken. After meeting with a genetic counselor, a personalized plan for that patient may entail earlier or more frequent prostate cancer screening, and support for helping the patient change behaviors that may further enhance pancreatic cancer risk, like smoking.

At the Sidney Kimmel Cancer Center at Jefferson, the Mens Genetic Risk centralizes these plans, and coordinates with the patients care team to tailor the individual health plan. Further discussions are also had with regard to cascade testing, or testing family members who may also be at risk. As such, genetic testing can impact not just the patient themselves, but family members as well.

Genetic testing might be recommended to someone if they have a strong family history of cancer, which may include several first-degree relatives parents, siblings and children with cancer; many relatives with the same type of cancer; relatives who were diagnosed at a younger-than-normal age; or a relative diagnosed with a rare cancer, such as a male with breast cancer.

Someone who has already been diagnosed with cancer may benefit from genetic testing as well, especially if they were diagnosed at a young age or have a family history of cancer. Cancers with a known hereditary component include breast, ovarian, uterine, prostate, colorectal, melanoma, pancreatic and stomach cancers.

Having a family history of cancer is not limited to a having a family history of thesamecancer. For example, and related to our case above, a man whose mother or sister had breast cancer might be at risk himself for prostate cancer.

It is also important to note that the presence of a gene mutation is also relevant when treating existing cancer. Certain genetic mutations are also associated with a greater risk of having an aggressive cancer and resistance to certain therapies, which can help your doctor manage specific tumor types.

Your results may help your doctor decide on the best treatment regimen, because researchers have found that some treatments are more effective in people with certain gene mutations. In fact, the FDA has recently approved cancer therapies that are only for patients whose tumors have specific gene alterations and it is expected that many more such targeted therapies will be approved and ready for use in treating cancer.

So what if you have been tested and you do not have an identified genetic risk? It is important to note that not having a family history of cancer or genetic risk of cancer does not guarantee that you will never develop cancer. With regard to family history, the National Cancer Institute notes that only 5-10% of cancers are due to inherited gene mutations.

Additionally, having a family history of cancer does not mean that you are certain to be diagnosed with cancer one day yourself. Genetic testing can help inform you of your genetic risk for certain diseases, but it does not inform you of your overall risk. Other factors that contribute to an increased risk for cancer include environmental factors and lifestyle choices, many of which are modifiable.

If you are considering genetic testing or have questions about whether you or your family should undergo testing, talk to your doctor or other health care providers. Talking to a health professional or genetic counselor can help you decide whether you would benefit from testing. They will collect your family and personal health history, explain what kind of information the test can provide you, and help you decide whether the test is right for you.

After undergoing genetic testing, it is important that you talk to your health care provider about what the results mean for you, whether positive or negative. The results can be confusing, and they can help you interpret your results, allay any fears, discuss potential implications for your family, and help you make an informed decision about how to proceed based on the results. Discussion with a specialist is important for future care decisions.

If appropriate, your doctor may discuss cancer risk-reduction strategies with you, like preventive surgery, medications that help reduce risk or lifestyle changes. They also may recommend alternative screening options to help detect the cancer early, such as beginning mammograms before age 40 or having a colonoscopy at 45 rather than 50.

In addition to the clinical genetic testing, a growing number of companies are making tests available to consumers that can provide insight into ones ancestry, as well as certain health information. There are a few things to keep in mind regarding these direct-to-consumer tests if you decide to go ahead with one.

Ancestry DNA tests are typically not clinical grade, meaning that the information is not of the established quality required to change someones health plan. Even if a cancer gene is suspected on these tests, confirmation would be required using a clinical-grade test that has been deemed valid and reliable for detecting cancer gene alterations.

In addition, many at-home tests are very small in scale, and leave out testing of many genes known to be influential in determining cancer risk. For example, an at-home test might screen for mutations in the BRCA1 and BRCA1 genes, but not for the genes associated with Lynch syndrome, an inherited disorder that increases the risk of several cancer types, including colorectal cancer.

There is a growing concern that negative results from an at-home test can provide consumers with a false sense of security. These tests should not be used as a substitute for the genetic counseling and testing you would receive from your health care provider, who will usually re-order a clinical test to confirm the results, and help you understand the results of the test.

Despite the importance of understanding personal genetic risk of cancer, there are justifiable concerns about privacy. This is an important concept for every person to consider. The Health Insurance Portability and Accountability Act protects your genetic data if you were tested through your health care provider. However, there are fewer protections with the direct-to-consumer DNA testing companies, so be sure to understand the companys privacy policy when signing up for services. Some companies may share your results with third parties, such as medical or pharmaceutical researchers.

A common concern for people considering genetic testing is discrimination based on their genetics. The Genetic Information Nondiscrimination Act is a federal law that protects individuals from genetic discrimination. GINA prohibits health insurers from discrimination based on the genetic information of enrollees, meaning they may not use genetic information to make decisions regarding eligibility, coverage, underwriting or premium-setting. However, GINA does not cover disability, life and long-term care insurance.

GINA also prevents employers who have at least 15 employees from using genetic information in employment decisions such as hiring, firing, promotions, pay and job assignments. Additionally, some states have enacted laws that offer additional protections against genetic discrimination. For more information on GINA and genetic discrimination, click here

In sum, cancer genetics is a rapidly evolving field, and the era is upon us wherein individual wellness plans will be as guided by genetic information as they are by vital signs. It was not long ago when the only genetic testing option was examining the BRCA1 and BRCA2 genes for inherited mutations associated with breast and ovarian cancers.

Fast-forwarding to 2020, we not only understand more about BRCA mutations, but we have discovered that there are many hundreds of other genes related to cancer development and progression. If you had BRCA testing many years ago or were told previously that you were ineligible for genetic testing, talk to your doctor.

As we learn more about genetic mutations and we continue to expand the recommendations for testing to include more people, your doctor might recommend that you undergo genetic testing now or consider additional genetic testing. Understanding your genetic code just might be a life saver!

Karen E. Knudsen, Ph.D., enterprise director at the Sidney Kimmel Cancer Center Jefferson Health, oversees cancer care and cancer research at all SKCC sites in the Greater Philadelphia region. She writes occasionally on topics related to cancer.

Visit link:
Genetic testing is helping prevent cancer and changing treatment plans - PhillyVoice.com

Recommendation and review posted by Bethany Smith

The cold case murder of Cedar Rapids teenager Michelle Martinko went unsolved for decades, until last month, when prosecutors won a guilty conviction by relying on 40-year-old crime scene and a family genealogy website. Its one of the first cases of its kind to go to trial but its raising questions about ethics and legality.

It was 1979, the week before Christmas when 18-year-old Michelle Martinko went to a brand new mall in Cedar Rapids to pick up a winter coat. But she never made it home that night; she was found stabbed to death in her parents Buick in the mall parking lot.

With no murder weapon and no clear motive, Martinkos killing haunted Cedar Rapids residents for decades. Generations of police officers worked the case.

They tested and retested DNA evidence that the male suspect left at the crime scene, but never got a match in the FBIs DNA database.

Then in 2018, they heard about a new tool. With the help of the private genetics firm Parabon NanoLabs, officers uploaded the suspects genetic profile to a public genealogy website called GEDmatch.

The site is somewhat similar to the better-known 23andMe or ancestry.com. Its a favorite of people looking for long-lost relatives, and unlike the other services its free to use.

After nearly 40 years of investigating, officers got a hit on GEDmatch: a distant cousin living in Washington State.

From there, the private firm built a family tree of potential suspects and officers began the tedious task of tracking them down, secretly following the men, waiting for them to throw away something they could test for DNA.

For 64-year-old Jerry Burns, it was a straw he used at a pizza restaurant in Manchester, Iowa.

Thirty-nine years to the day after Martinko was killed, Officer Matt Denlinger and his partner J.D. Smith questioned Burns, in the city where hed lived his whole life, just an hour from the crime scene.

They secretly recorded the interaction.

Did you murder someone that night, Jerry? Denlinger asked the man.

Test the DNA, Burns said.

Jerry, Denlinger continued.

Test the DNA, he replied.

Why did this happen Jerry? Denlinger questioned.

Test the DNA, he said again.

What happened? the officer asked.

I dont know, Burns replied.

Last month, a jury convicted Burns of first degree murder based on the DNA evidence. Burns case is thought to be just the third in the country to go to trial.

"I see a utility in this, I do. But right now it's like the Wild, Wild West where people just kind of doing what they do, because there are no rules." State Sen. Charles Sydnor, D-Md.

Other similar cases, including that of the alleged Golden State Killer in California, are at various stages of investigation or are awaiting trial. The high-profile California case made national news in April 2018, when officers tracked down the accused serial killer after testing his trash for DNA. The development is considered a major breakthrough and has sparked similar investigations in other cases across the country.

But the use genetic genealogy by law enforcement officers remains controversial. In recent years, GEDmatch has changed its policies to alert users that investigators have an interest in the site. Where in the past police had access to the profiles of all of the sites approximately one million users, those users are now required to opt in if they want to participate in searches by police.

State lawmakers in several states are considering restricting police access to consumer DNA databases.

At first, State Sen. Charles Sydnor ,D-Md, wanted to ban the practice. But after advocates pushed back, hes seeking a compromise.

I see a utility in this, I do, Sydnor said. But right now its like the Wild, Wild West where people just kind of doing what they do, because there are no rules, Sydnor said.

There are some rules. The Department of Justice has put out guidance on how officers should use genetic genealogy. But its just that, guidance. And theres a lot of interest in this technology.

Parabon NanoLabs, which worked on the Burns case and is one of the go-to private contractors in the field, says theyve now worked with agencies in 47 states.

"We could set up a society where we catch every bad guy. But at the same time we would imprison ourselves to the government." - Michael Melendez, Libertas Institute

Consumer database searches are generally reserved for the hardest-to-solve violent crimes, often cold cases.

But sometimes investigators dont really know who theyre searching for, and dont have a warrant for their search.

Sydnors bill would put limitations on this practice, by restricting familial searches of genetic profiles to a smaller web of family members.

[In larger searches] youre implicating a number of people who havewhere theres absolutely no probable cause, they have nothing to do with whatever crime it is youre trying to solve but yet youre pulling their genetic information, Sydnor said.

Michael Melendez of the Libertarian think tank Libertas Institute has helped write a bill filed in Utah. He says he doesnt doubt that a larger scale of what some call genetic surveillance could help officers solve more crimes.

We could set up a society where we catch every bad guy, Melendez said. But at the same time we would imprison ourselves to the government.

"You can make an argument especially in light of recent Supreme Court precedent that obtaining information from either a public or a private database without a warrant is unconstitutional," - Christopher Slobogin, Vanderbilt University Law School

The practice of warrantless searches of the consumer databases also raises concerns for Christopher Slobogin, director of the Criminal Justice Program at the Vanderbilt University Law School.

Oh yeah, I think they definitely gotta get a warrant, Slobogin said. You can make an argument especially in light of recent Supreme Court precedent that obtaining information from either a public or a private database without a warrant is unconstitutional.

In fact, Jerry Burns lawyer argued that using the database in his case was an unconstitutional search and in violation of his Fourth Amendment privacy rights.

Legal experts say its the first time the constitutionality of these searches has been raised in court.

But the judge in the case shot it down citing whats known as the third party doctrine, writing that because GEDmatch users shared their DNA with a third party (GEDmatch), they do not have an expectation of privacy over that information.

In the 2018 case Carpenter v. United States, U.S. Supreme Court justices hinted they could re-examine modern privacy rights to digital information. But its not clear how that could impact these consumer databases.

In the meantime, Janelle Stonebraker is thankful that investigators have this option. She is the sister of Michelle Martinko, and said she had given up hope on seeing a resolution in the case when investigators called to let her know they would be re-examining the crime scene DNA.

"That of course, was an amazing revelation and reorienting of thought and feelings. Because who else could it have been all those years?" - Janelle Stonebraker, sister of Michelle Martinko

The use of genetics in the case led to elimination of more than a hundred potential suspects. For Stonebraker, that meant the exoneration of her sisters friends and ex-boyfriends, who had long been scrutinized by police.

That of course, was an amazing revelation and reorienting of thought and feelings. Because who else could it have been all those years, in our estimation, Stonebraker said.

Stonebraker said she is aware of the criticisms of the investigative method and has family members who are concerned about how genetic information could be used to discriminate against patients in healthcare settings.

I think always the technology is ahead of the law, she said. So I think it will all have to be looked at, they will have to analyze all of the permutations and misuses and see what is see what is necessary.

Another person thankful for this innovation in forensic investigation is Brandy Jennings. It was Jennings DNA that led officers to Jerry Burns in the first place. She says for her, privacy was never a concern.

I dont regret it. I dont think that its a bad thing. I dont think I wouldve chosen differently. You know, its kinda like one of those things, if you dont have anything to hide whats the big deal? she said. To me anyways.

Like 200,000 people on GEDmatch, Jennings has agreed to let officers use her DNA in their searches.

As of now theres not much stopping them from doing just that.

See the article here:
Police Used A Genealogy Website To Crack An Iowa Cold Case. The Tool Is Raising Concerns Elsewhere. - Iowa Public Radio

Recommendation and review posted by Bethany Smith

A new study investigates the relationship between hearing loss and cognitive decline. The scientists have found that after 18 months of hearing aid use, participants performance on some cognitive tests improved.

Dementia becomes more likely as we age so as the populations average age steadily rises, the prevalence of dementia climbs accordingly.

To date, there is no cure for dementia, and researchers are avidly investigating ways to treat and prevent it.

Because cognitive decline precedes dementia, understanding how to curb this decline could help reduce the risk of dementia.

A group of researchers from the University of Melbourne, in Australia, is particularly interested in the potential role of another condition that becomes more prevalent with age hearing loss.

According to the authors of the study, published in the Journal of Clinical Medicine, age-related hearing loss affects 3060% of people aged over 65 and 7090% of those aged 85 or older.

The authors explain how, Hearing loss is associated with many comorbidities, including poorer physical health, anxiety, depression, loneliness, and isolation. Yet, they note, hearing loss is undertreated, with only 1 in 20 working adults aged 5070 wearing hearing aids.

Importantly, medical researchers now consider hearing loss to be a risk factor for dementia.

It follows that using a hearing aid might reduce the risk of dementia or slow its progress. However, to date, the evidence has been contradictory, with some studies finding benefits and others finding none.

Earlier research had certain limitations. For instance, some studies only had access to relatively small sample sizes or relied on self-reported hearing loss and cognitive decline.

Other studies did not capture information about education level, mood, exercise frequency, and other factors that can also influence cognitive decline.

The latest study involved 99 adult participants aged 6282 with hearing loss who were new to hearing aids.

The scientists assessed the participants before they had acquired the hearing aids and then 18 months later. The team was also interested in observing any differences between males and females.

The researchers collated information about hearing, speech perception, levels of physical activity, the quality of life, mood, loneliness, and general health.

They also assessed cognitive performance in five domains: psychomotor function, attention, working memory, visual learning, and executive function.

Primarily, the authors were interested in the relationship between hearing loss and cognitive impairment; they also wanted to track whether wearing a hearing aid, over time, might influence cognitive ability.

At the 18-month mark, there was a pronounced improvement in self-reported speech perception in quiet situations. As the authors explain, this has been widely reported for users of hearing aids.

When the scientists assessed cognitive performance after 18 months, they found that average scores across the battery of cognitive tests had not improved.

However, when they assessed executive function separately, they found significant improvements. Of the 99 participants, only one male had experienced a decline in executive function.

Executive function refers to a set of cognitive tools that helps us navigate our everyday lives. It includes flexible thinking, working memory, and self-control.

This increase in executive function was more pronounced in females than males.

When the researchers analyzed cognitive data from females only, they found significant improvements in working memory, visual attention, and visual learning, alongside improvements in executive function.

The researchers had also monitored how often the participants used their hearing aids. They found that those who used their devices most regularly experienced greater improvements in cognitive performance.

The authors believe that this difference between sexes might be, at least partially, due to how often the participants used their hearing aids; females used their devices 56.3% of the time, whereas males used them just 33.3% of the time.

The authors are quick to note that their sample is not representative; on average, the participants were more highly educated than the general population. This means that they are likely to have more cognitive reserves and, therefore, might be more resistant to cognitive decline.

Yet even among highly educated people, cognitive performance is not expected to improve in this age group. Overall, the authors conclude:

Despite the small sample size to date, both the observed relative stability and clinically and statistically significant improvement in cognition seen in this initial participant group after 18 months of hearing aid use are exciting and encouraging.

When the authors looked at measures of quality of life, they noted a significant improvement over the 18 months.

Again, they found a difference between the sexes, with a greater proportion of females than males reporting improved quality of life after 18 months of hearing aid use.

Earlier studies have shown links between hearing loss and mental health issues. In the current study, at the 18-month mark, mental health, on average, was good.

However, the participants in this study had relatively good mental health at baseline. Again, the sample is not representative of society at large, so to fully assess the impact of hearing aids on mental health, scientists will need to carry out more research with larger, more diverse samples of the population.

Although some risk factors for dementia, such as advancing age and genetics, cannot be altered, others can be minimized, and one modifiable risk factor is hearing loss.

Wearing a hearing aid many not prevent dementia. But, as the authors write, If the onset of functional impairment could even be delayed by only a few years for some people, this would be a significant achievement.

View original post here:
Cognitive decline: Could hearing aids reduce the risk? - Medical News Today

Recommendation and review posted by Bethany Smith

Male Breast Cancer Treatment Market Size, Type, Application, and Regional Analysis, Trading Analysis, Industry Analysis, Premium Insights, Patent Analysis, Market Attractiveness, Competitive Landscape, Traders/Distributors, Key Buyers, Forecasts 2020 2025

The Global Male Breast Cancer Treatment Market study exhibits a comprehensive analysis of the present and future market trends across the globe. The study presented by Reportspedia presents convincing data referring to the commercialization aspects, industry dimension, and profit estimation of the market. The latest report on the Male Breast Cancer Treatment industry provides the end-to-end analysis of this business vertical, and includes the detailed information about the industry, with respect to key constraints such as the present market size, revenue, market share, periodic deliverables, and profits estimations for the estimate period of 2020 2025.

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The Leading Companies Included In the Reports Are:

PfizerRocheGlaxoSmithKlineSanofiNovartisBayerBristol-Myers SquibbEli LillyAstraZenecaTeva PharmaceuticalSun PharmaceuticalBioNumerik PharmaceuticalsSeattle GeneticsAccord Healthcare

Trade analysis of the market is also the key aspects of the report as it provides information on the import and export of the product across the globe. Analysis tools like SWOT analysis and Porters five force model have been provided to present a perfect in-depth knowledge about Male Breast Cancer Treatment market. The industry is also been analyzed in terms of value chain analysis and analysis of regulatory policies.

The study also illustrates the competitive landscape of foremost manufacturers in the industry with their diverse portfolio and geographical expansion activities. The Male Breast Cancer Treatment market report byReportspedia also includes participants financial overview which consists of an assessment of revenue outcomes, sales volume, gross margin, cash flow, capital investment, and growth rate which will allow clients to gain intact knowledge of participants financial strengths and position in the global Male Breast Cancer Treatment industry.

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Market Size Segmentation by Region (or Countries), Types and Applications:

Key Focused Regions in the Male Breast Cancer Treatment market:

South America (Brazil, Argentina)

The Middle East & Africa(South Africa, Saudi Arabia)

Europe (Spain, U.K., Italy, Germany, Russia, France)

North America (U.S., Mexico, Canada)

Asia-Pacific (China, Japan, India, Southeast Asia)

Global Male Breast Cancer Treatment Market Size Segmentation by Type:

MedicationChemotherapyOthers

Global Male Breast Cancer Treatment Market Size Segmentation by Application:

HospitalsClinicsOthers

Report Objectives:

1) Examination of the global Male Breast Cancer Treatment market size by value and size.

2) To accurately calculate the market segments, consumption, and other dynamic factors of the various units of the market.

3) Determination of the key dynamics of the market.

4) To highpoint key trends in the market in terms of manufacturing, revenue and sales.

5) To summarize the top players of Global Male Breast Cancer Treatment industry and show how they compete in the industry.

6) Study of industry procedures and costs, product pricing and various developments associated with them.

7) To showcase the performance of different regions and countries in the Global Male Breast Cancer Treatment market.

The Report Answers the key Questions

What are the important trends and dynamics?

Where will most development take place in the long term?

Which regulation thats will impact the industry

What does the competitive landscape look like?

What the openings are yet to come?

TOC of Male Breast Cancer Treatment Market Report Includes:

1 Industry Overview of Male Breast Cancer Treatment Market

2 Industry Chain Analysis

3 Manufacturing Technology

4 Major Manufacturers Analysis

5 Global Productions, Revenue and Price Analysis by Regions, Creators, Types and Applications

6 Global and Foremost Regions Capacity, Production, Revenue and Growth Rate of Male Breast Cancer Treatment market (2015-2019)

7 Consumption Volumes, Consumption Value, Import, Export and Trade Price Study of Male Breast Cancer Treatment market by Regions

8 Gross and Gross Margin Examination

9 Marketing Traders or Distributor Examination

10 Worldwide Impacts on Male Breast Cancer Treatment Industry

11 Development Trend Analysis

12 Contact information of Male Breast Cancer Treatment

13 New Project Investment Feasibility Analysis

14 Conclusion of the Global Male Breast Cancer Treatment Industry 2020 Market Research Report

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Global Male Breast Cancer Treatment Market 2020 Size, Share, Growth and its Detail Analysis and Forecast By 2025 - News Times

Recommendation and review posted by Bethany Smith

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It is normal for women to shed some hair each day, but when bald patches or thinning occurs, it may be due to female pattern baldness.

Shedding about 50 to 100 hairs a day is considered normal, but new growth will typically replace these hairs. If someone has female pattern baldness, however, the lost hair is not renewed.

In this article, we look at the causes and risk factors for female pattern baldness, as well as treatment and prevention.

Female pattern baldness is a type of hair loss that affects women. The medical name for the condition is androgenetic alopecia.

Although both men and women may experience hair loss, it is not as widespread in women as in men and appears differently.

Men who have hair loss tend to develop a receding hairline and bald spots. Women with female pattern baldness usually experience general hair thinning, which affects the volume of their hair.

In women, the first signs of female pattern baldness may be a widening part or a feeling that the hair does not feel as thick as usual. Although the scalp may be visible, the hairline usually does not recede.

Hair loss is less frequent in women than in men, but it still occurs often. Female pattern baldness increases with age, and fewer than 50 percent of women have a full head of hair for their entire life.

Genetics appears to be a significant factor in developing female pattern baldness, which means it runs in families. Women can inherit the gene for pattern baldness from either parent.

Female pattern baldness tends to be more common as a woman ages and reaches midlife, although it can begin earlier.

It often develops after menopause, so hormonal changes may also be a contributing factor.

Female pattern baldness is largely thought to occur due to genetics. However, it may also develop due to an underlying condition that affects the production of the hormone androgen.

Androgen is a hormone that plays a role in pattern baldness. Tumors of the pituitary gland or ovary, which secrete androgen, may also lead to hair loss.

Other causes of hair loss in women include:

The type of treatment recommended will depend on the extent of the hair loss, in addition to other factors.

Treatment for female pattern baldness can help prevent future hair loss and may result in regrowth of some hair. In most cases, long-term treatment is needed to prevent hair loss from recurring.

Treatment options include:

Minoxidil is a topical medication that is used to treat hair loss in both men and women. The treatment is applied to the scalp every day and may stimulate hair growth, as well as prevent further hair thinning.

Minoxidil can take 6 months to a year to produce visible results and does not work for everyone. Side effects can include dryness, redness, and itching. Hair loss may return after a person stops using the product.

One well-known brand of Minoxidil is Rogaine, which is available to buy in many pharmacies and online.

One of the most common oral medications used to treat female pattern baldness is spironolactone, which is a diuretic. Diuretics remove excess water from the body.

The medication may also block the production of androgen, which may prevent hair loss and help hair regrow. Spironolactone can cause side effects, such as dry mouth, nausea, and dizziness.

Women who are pregnant should not take spironolactone due to a possibility that it might cause congenital disabilities.

Some women may choose to have a hair transplant. Various techniques may be used to perform hair transplantation.

Usually, hair loss affects only some areas of the scalp. During a hair transplant, a doctor removes hair from an area with healthy hair growth and transplants it to another spot where the hair is missing.

The area from which the doctor transplants the hair usually remains unaffected by hair loss. The doctor performs the procedure while a person is awake, and it takes several hours. A person will be given a local anesthetic to prevent pain.

Some people may wish to try at-home laser treatment for hair loss. These devices work by emitting low levels of laser light to stimulate hair regrowth.

According to some research, low-level laser light therapy can stimulate hair growth in women and men. However, additional studies are needed to determine the effectiveness of this type of treatment, as it is possible that laser treatment companies may have partially funded this research.

As female pattern baldness may be genetic, it is not always preventable. However, there are steps a woman can take to keep hair as healthy as possible to prevent breakage and damage.

Consider the following hair care tips:

Female pattern baldness can be distressing and affect a persons self-confidence and self-image. Women who experience excessive hair loss should talk with their doctor or dermatologist, who can help determine the cause and best treatment option.

Early diagnosis can help a person develop a treatment plan that prevents further hair loss. Treatments are available that may help restore hair growth. The effectiveness may vary depending on the treatment selected and the amount of hair loss.

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Female pattern baldness: Causes, treatment, and prevention

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Ritual cutting or removal of some or all of the external female genitalia

Female genital mutilation (FGM), also known as female genital cutting and female circumcision,[a] is the ritual cutting or removal of some or all of the external female genitalia. The practice is found in Africa, Asia and the Middle East, and within communities from countries in which FGM is common. UNICEF estimated in 2016 that 200 million women living today in 30 countries27 African countries, Indonesia, Iraqi Kurdistan and Yemenhave undergone the procedures.[3]

Typically carried out by a traditional circumciser using a blade, FGM is conducted from days after birth to puberty and beyond. In half of the countries for which national figures are available, most girls are cut before the age of five.[6] Procedures differ according to the country or ethnic group. They include removal of the clitoral hood and clitoral glans; removal of the inner labia; and removal of the inner and outer labia and closure of the vulva. In this last procedure, known as infibulation, a small hole is left for the passage of urine and menstrual fluid; the vagina is opened for intercourse and opened further for childbirth.

The practice is rooted in gender inequality, attempts to control women's sexuality, and ideas about purity, modesty and beauty. It is usually initiated and carried out by women, who see it as a source of honour and fear that failing to have their daughters and granddaughters cut will expose the girls to social exclusion.[8] Adverse health effects depend on the type of procedure; they can include recurrent infections, difficulty urinating and passing menstrual flow, chronic pain, the development of cysts, an inability to get pregnant, complications during childbirth, and fatal bleeding. There are no known health benefits.[9]

There have been international efforts since the 1970s to persuade practitioners to abandon FGM, and it has been outlawed or restricted in most of the countries in which it occurs, although the laws are poorly enforced. Since 2010, the United Nations has called upon healthcare providers to stop performing all forms of the procedure, including reinfibulation after childbirth and symbolic "nicking" of the clitoral hood.[10] The opposition to the practice is not without its critics, particularly among anthropologists, who have raised difficult questions about cultural relativism and the universality of human rights.[11]

Until the 1980s, FGM was widely known in English as female circumcision, implying an equivalence in severity with male circumcision. From 1929, the Kenya Missionary Council referred to it as the sexual mutilation of women, following the lead of Marion Scott Stevenson, a Church of Scotland missionary. References to the practice as mutilation increased throughout the 1970s.[13] In 1975 Rose Oldfield Hayes, an American anthropologist, used the term female genital mutilation in the title of a paper in American Ethnologist, and four years later Fran Hosken, an Austrian-American feminist writer, called it mutilation in her influential The Hosken Report: Genital and Sexual Mutilation of Females. The Inter-African Committee on Traditional Practices Affecting the Health of Women and Children began referring to it as female genital mutilation in 1990, and the World Health Organization (WHO) followed suit in 1991.[16] Other English terms include female genital cutting (FGC) and female genital mutilation/cutting (FGM/C), preferred by those who work with practitioners.[13]

In countries where FGM is common, the practice's many variants are reflected in dozens of terms, often alluding to purification.[17] In the Bambara language, spoken mostly in Mali, it is known as bolokoli ("washing your hands") and in the Igbo language in eastern Nigeria as isa aru or iwu aru ("having your bath").[b] Other terms include khifad, tahoor, quodiin, irua, bondo, kuruna, negekorsigin, and kene-kene. A common Arabic term for purification has the root t-h-r, used for male and female circumcision (tahur and tahara). It is also known in Arabic as khaf or khifa. Communities may refer to FGM as "pharaonic" for infibulation and "sunna" circumcision for everything else. Sunna means "path or way" in Arabic and refers to the tradition of Muhammad, although none of the procedures are required within Islam. The term infibulation derives from fibula, Latin for clasp; the Ancient Romans reportedly fastened clasps through the foreskins or labia of slaves to prevent sexual intercourse. The surgical infibulation of women came to be known as pharaonic circumcision in Sudan, and as Sudanese circumcision in Egypt. In Somalia, it is known simply as qodob ("to sew up").

The procedures are generally performed by a traditional circumciser (cutter or exciseuse) in the girls' homes, with or without anaesthesia. The cutter is usually an older woman, but in communities where the male barber has assumed the role of health worker he will also perform FGM.[26][c] When traditional cutters are involved, non-sterile devices are likely to be used, including knives, razors, scissors, glass, sharpened rocks and fingernails. According to a nurse in Uganda, quoted in 2007 in The Lancet, a cutter would use one knife on up to 30 girls at a time. Health professionals are often involved in Egypt, Kenya, Indonesia and Sudan; in Egypt 77 percent of FGM procedures, and in Indonesia over 50 percent, were performed by medical professionals as of 2008 and 2016.[30][3] Women in Egypt reported in 1995 that a local anaesthetic had been used on their daughters in 60 percent of cases, a general anaesthetic in 13 percent, and neither in 25 percent (two percent were missing/don't know).[31]

The WHO, UNICEF and UNFPA issued a joint statement in 1997 defining FGM as "all procedures involving partial or total removal of the external female genitalia or other injury to the female genital organs whether for cultural or other non-therapeutic reasons".[13] The procedures vary according to ethnicity and individual practitioners; during a 1998 survey in Niger, women responded with over 50 terms when asked what was done to them.[17] Translation problems are compounded by the women's confusion over which type of FGM they experienced, or even whether they experienced it. Studies have suggested that survey responses are unreliable. A 2003 study in Ghana found that in 1995 four percent said they had not undergone FGM, but in 2000 said they had, while 11 percent switched in the other direction. In Tanzania in 2005, 66 percent reported FGM, but a medical exam found that 73 percent had undergone it. In Sudan in 2006, a significant percentage of infibulated women and girls reported a less severe type.

Standard questionnaires from United Nations bodies ask women whether they or their daughters have undergone the following: (1) cut, no flesh removed (symbolic nicking); (2) cut, some flesh removed; (3) sewn closed; or (4) type not determined/unsure/doesn't know.[d] The most common procedures fall within the "cut, some flesh removed" category and involve complete or partial removal of the clitoral glans.[36] The World Health Organization (a UN agency) created a more detailed typology in 1997: Types III vary in how much tissue is removed; Type III is equivalent to the UNICEF category "sewn closed"; and Type IV describes miscellaneous procedures, including symbolic nicking.[37]

Type I is "partial or total removal of the clitoris and/or the prepuce". Type Ia[e] involves removal of the clitoral hood only. This is rarely performed alone.[f] The more common procedure is Type Ib (clitoridectomy), the complete or partial removal of the clitoral glans (the visible tip of the clitoris) and clitoral hood.[1][40] The circumciser pulls the clitoral glans with her thumb and index finger and cuts it off.[g]

Type II (excision) is the complete or partial removal of the inner labia, with or without removal of the clitoral glans and outer labia. Type IIa is removal of the inner labia; Type IIb, removal of the clitoral glans and inner labia; and Type IIc, removal of the clitoral glans, inner and outer labia. Excision in French can refer to any form of FGM.[1]

Type III (infibulation or pharaonic circumcision), the "sewn closed" category, is the removal of the external genitalia and fusion of the wound. The inner and/or outer labia are cut away, with or without removal of the clitoral glans.[h] Type III is found largely in northeast Africa, particularly Djibouti, Eritrea, Ethiopia, Somalia, and Sudan (although not in South Sudan). According to one 2008 estimate, over eight million women in Africa are living with Type III FGM.[i] According to UNFPA in 2010, 20 percent of women with FGM have been infibulated.[43] In Somalia, according to Edna Adan Ismail, the child squats on a stool or mat while adults pull her legs open; a local anaesthetic is applied if available:

The element of speed and surprise is vital and the circumciser immediately grabs the clitoris by pinching it between her nails aiming to amputate it with a slash. The organ is then shown to the senior female relatives of the child who will decide whether the amount that has been removed is satisfactory or whether more is to be cut off.

After the clitoris has been satisfactorily amputated... the circumciser can proceed with the total removal of the labia minora and the paring of the inner walls of the labia majora. Since the entire skin on the inner walls of the labia majora has to be removed all the way down to the perineum, this becomes a messy business. By now, the child is screaming, struggling, and bleeding profusely, which makes it difficult for the circumciser to hold with bare fingers and nails the slippery skin and parts that are to be cut or sutured together....

Having ensured that sufficient tissue has been removed to allow the desired fusion of the skin, the circumciser pulls together the opposite sides of the labia majora, ensuring that the raw edges where the skin has been removed are well approximated. The wound is now ready to be stitched or for thorns to be applied. If a needle and thread are being used, close tight sutures will be placed to ensure that a flap of skin covers the vulva and extends from the mons veneris to the perineum, and which, after the wound heals, will form a bridge of scar tissue that will totally occlude the vaginal introitus.[44]

The amputated parts might be placed in a pouch for the girl to wear. A single hole of 23mm is left for the passage of urine and menstrual fluid.[j] The vulva is closed with surgical thread, or agave or acacia thorns, and might be covered with a poultice of raw egg, herbs and sugar. To help the tissue bond, the girl's legs are tied together, often from hip to ankle; the bindings are usually loosened after a week and removed after two to six weeks. If the remaining hole is too large in the view of the girl's family, the procedure is repeated.

The vagina is opened for sexual intercourse, for the first time either by a midwife with a knife or by the woman's husband with his penis. In some areas, including Somaliland, female relatives of the bride and groom might watch the opening of the vagina to check that the girl is a virgin. The woman is opened further for childbirth (defibulation or deinfibulation), and closed again afterwards (reinfibulation). Reinfibulation can involve cutting the vagina again to restore the pinhole size of the first infibulation. This might be performed before marriage, and after childbirth, divorce and widowhood.[k] Hanny Lightfoot-Klein interviewed hundreds of women and men in Sudan in the 1980s about sexual intercourse with Type III:

The penetration of the bride's infibulation takes anywhere from 3 or 4 days to several months. Some men are unable to penetrate their wives at all (in my study over 15%), and the task is often accomplished by a midwife under conditions of great secrecy, since this reflects negatively on the man's potency. Some who are unable to penetrate their wives manage to get them pregnant in spite of the infibulation, and the woman's vaginal passage is then cut open to allow birth to take place.... Those men who do manage to penetrate their wives do so often, or perhaps always, with the help of the "little knife". This creates a tear which they gradually rip more and more until the opening is sufficient to admit the penis.[49]

Type IV is "[a]ll other harmful procedures to the female genitalia for non-medical purposes", including pricking, piercing, incising, scraping and cauterization.[1] It includes nicking of the clitoris (symbolic circumcision), burning or scarring the genitals, and introducing substances into the vagina to tighten it.[50][51] Labia stretching is also categorized as Type IV.[52] Common in southern and eastern Africa, the practice is supposed to enhance sexual pleasure for the man and add to the sense of a woman as a closed space. From the age of eight, girls are encouraged to stretch their inner labia using sticks and massage. Girls in Uganda are told they may have difficulty giving birth without stretched labia.[l][54]

A definition of FGM from the WHO in 1995 included gishiri cutting and angurya cutting, found in Nigeria and Niger. These were removed from the WHO's 2008 definition because of insufficient information about prevalence and consequences.[52] Angurya cutting is excision of the hymen, usually performed seven days after birth. Gishiri cutting involves cutting the vagina's front or back wall with a blade or penknife, performed in response to infertility, obstructed labour and other conditions. In a study by Nigerian physician Mairo Usman Mandara, over 30 percent of women with gishiri cuts were found to have vesicovaginal fistulae (holes that allow urine to seep into the vagina).[55]

FGM harms women's physical and emotional health throughout their lives.[56] It has no known health benefits.[9] The short-term and late complications depend on the type of FGM, whether the practitioner has had medical training, and whether they used antibiotics and sterilized or single-use surgical instruments. In the case of Type III, other factors include how small a hole was left for the passage of urine and menstrual blood, whether surgical thread was used instead of agave or acacia thorns, and whether the procedure was performed more than once (for example, to close an opening regarded as too wide or re-open one too small).

Common short-term complications include swelling, excessive bleeding, pain, urine retention, and healing problems/wound infection. A 2014 systematic review of 56 studies suggested that over one in ten girls and women undergoing any form of FGM, including symbolic nicking of the clitoris (Type IV), experience immediate complications, although the risks increased with Type III. The review also suggested that there was under-reporting.[m] Other short-term complications include fatal bleeding, anaemia, urinary infection, septicaemia, tetanus, gangrene, necrotizing fasciitis (flesh-eating disease), and endometritis.[59] It is not known how many girls and women die as a result of the practice, because complications may not be recognized or reported. The practitioners' use of shared instruments is thought to aid the transmission of hepatitis B, hepatitis C and HIV, although no epidemiological studies have shown this.

Late complications vary depending on the type of FGM. They include the formation of scars and keloids that lead to strictures and obstruction, epidermoid cysts that may become infected, and neuroma formation (growth of nerve tissue) involving nerves that supplied the clitoris. An infibulated girl may be left with an opening as small as 23mm, which can cause prolonged, drop-by-drop urination, pain while urinating, and a feeling of needing to urinate all the time. Urine may collect underneath the scar, leaving the area under the skin constantly wet, which can lead to infection and the formation of small stones. The opening is larger in women who are sexually active or have given birth by vaginal delivery, but the urethra opening may still be obstructed by scar tissue. Vesicovaginal or rectovaginal fistulae can develop (holes that allow urine or faeces to seep into the vagina). This and other damage to the urethra and bladder can lead to infections and incontinence, pain during sexual intercourse and infertility. Painful periods are common because of the obstruction to the menstrual flow, and blood can stagnate in the vagina and uterus. Complete obstruction of the vagina can result in hematocolpos and hematometra (where the vagina and uterus fill with menstrual blood). The swelling of the abdomen and lack of menstruation can resemble pregnancy; Asma El Dareer, a Sudanese physician, reported in 1979 that a girl in Sudan with this condition was killed by her family.

FGM may place women at higher risk of problems during pregnancy and childbirth, which are more common with the more extensive FGM procedures. Infibulated women may try to make childbirth easier by eating less during pregnancy to reduce the baby's size.[65]:99 In women with vesicovaginal or rectovaginal fistulae, it is difficult to obtain clear urine samples as part of prenatal care, making the diagnosis of conditions such as pre-eclampsia harder. Cervical evaluation during labour may be impeded and labour prolonged or obstructed. Third-degree laceration (tears), anal-sphincter damage and emergency caesarean section are more common in infibulated women.[65]

Neonatal mortality is increased. The WHO estimated in 2006 that an additional 1020 babies die per 1,000 deliveries as a result of FGM. The estimate was based on a study conducted on 28,393 women attending delivery wards at 28 obstetric centres in Burkina Faso, Ghana, Kenya, Nigeria, Senegal and Sudan. In those settings all types of FGM were found to pose an increased risk of death to the baby: 15 percent higher for Type I, 32 percent for Type II, and 55 percent for Type III. The reasons for this were unclear, but may be connected to genital and urinary tract infections and the presence of scar tissue. According to the study, FGM was associated with an increased risk to the mother of damage to the perineum and excessive blood loss, as well as a need to resuscitate the baby, and stillbirth, perhaps because of a long second stage of labour.[66][67]

According to a 2015 systematic review there is little high-quality information available on the psychological effects of FGM. Several small studies have concluded that women with FGM suffer from anxiety, depression and post-traumatic stress disorder. Feelings of shame and betrayal can develop when women leave the culture that practises FGM and learn that their condition is not the norm, but within the practising culture they may view their FGM with pride, because for them it signifies beauty, respect for tradition, chastity and hygiene. Studies on sexual function have also been small. A 2013 meta-analysis of 15 studies involving 12,671 women from seven countries concluded that women with FGM were twice as likely to report no sexual desire and 52 percent more likely to report dyspareunia (painful sexual intercourse). One third reported reduced sexual feelings.[68]

Aid agencies define the prevalence of FGM as the percentage of the 1549 age group that has experienced it. These figures are based on nationally representative household surveys known as Demographic and Health Surveys (DHS), developed by Macro International and funded mainly by the United States Agency for International Development (USAID); and Multiple Indicator Cluster Surveys (MICS) conducted with financial and technical help from UNICEF. These surveys have been carried out in Africa, Asia, Latin America and elsewhere roughly every five years, since 1984 and 1995 respectively.[70] The first to ask about FGM was the 19891990 DHS in northern Sudan. The first publication to estimate FGM prevalence based on DHS data (in seven countries) was written by Dara Carr of Macro International in 1997.

Questions the women are asked during the surveys include: "Was the genital area just nicked/cut without removing any flesh? Was any flesh (or something) removed from the genital area? Was your genital area sewn?"[72] Most women report "cut, some flesh removed" (Types I and II).[73]

Type I is the most common form in Egypt, and in the southern parts of Nigeria. Type III (infibulation) is concentrated in northeastern Africa, particularly Djibouti, Eritrea, Somalia and Sudan. In surveys in 20022006, 30 percent of cut girls in Djibouti, 38 percent in Eritrea, and 63 percent in Somalia had experienced Type III.[76] There is also a high prevalence of infibulation among girls in Niger and Senegal,[77] and in 2013 it was estimated that in Nigeria three percent of the 014 age group had been infibulated.[78] The type of procedure is often linked to ethnicity. In Eritrea, for example, a survey in 2002 found that all Hedareb girls had been infibulated, compared with two percent of the Tigrinya, most of whom fell into the "cut, no flesh removed" category.[17]

FGM is mostly found in what Gerry Mackie called an "intriguingly contiguous" zone in Africaeast to west from Somalia to Senegal, and north to south from Egypt to Tanzania.[79] Nationally representative figures are available for 27 countries in Africa, as well as Indonesia, Iraqi Kurdistan and Yemen. Over 200 million women and girls are thought to be living with FGM in those 30 countries.[3][80]

The highest concentrations among the 1549 age group are in Somalia (98 percent), Guinea (97 percent), Djibouti (93 percent), Egypt (91 percent) and Sierra Leone (90 percent).[81] As of 2013, 27.2 million women had undergone FGM in Egypt, 23.8 million in Ethiopia, and 19.9 million in Nigeria.[82] There is a high concentration in Indonesia, where according to UNICEF Type I (clitoridectomy) and Type IV (symbolic nicking) are practised; the Indonesian Ministry of Health and Indonesian Ulema Council both say the clitoris should not be cut. The prevalence rate for the 011 group in Indonesia is 49 percent (13.4 million).[80]:2 Smaller studies or anecdotal reports suggest that FGM is also practised in Colombia, Jordan, Oman, Saudi Arabia and parts of Malaysia;[83] in the United Arab Emirates;[3] and in India[n] by the Dawoodi Bohra.[84][o] It is found within immigrant communities around the world.[87]

Prevalence figures for the 1519 age group and younger show a downward trend.[p] For example, Burkina Faso fell from 89 percent (1980) to 58 percent (2010); Egypt from 97 percent (1985) to 70 percent (2015); and Kenya from 41 percent (1984) to 11 percent (2014).[89] Beginning in 2010, household surveys asked women about the FGM status of all their living daughters.[90] The highest concentrations among girls aged 014 were in Gambia (56 percent), Mauritania (54 percent), Indonesia (49 percent for 011) and Guinea (46 percent).[3] The figures suggest that a girl was one third less likely in 2014 to undergo FGM than she was 30 years ago.[91] According to a 2018 study published in BMJ Global Health, the prevalence within the 014 year old group fell in East Africa from 71.4 percent in 1995 to 8 percent in 2016; in North Africa from 57.7 percent in 1990 to 14.1 percent in 2015; and in West Africa from 73.6 percent in 1996 to 25.4 percent in 2017.[92] If the current rate of decline continues, the number of girls cut will nevertheless continue to rise because of population growth, according to UNICEF in 2014; they estimate that the figure will increase from 3.6 million a year in 2013 to 4.1 million in 2050.[q]

Surveys have found FGM to be more common in rural areas, less common in most countries among girls from the wealthiest homes, and (except in Sudan and Somalia) less common in girls whose mothers had access to primary or secondary/higher education. In Somalia and Sudan the situation was reversed: in Somalia the mothers' access to secondary/higher education was accompanied by a rise in prevalence of FGM in their daughters, and in Sudan access to any education was accompanied by a rise.[94]

FGM is not invariably a rite of passage between childhood and adulthood, but is often performed on much younger children. Girls are most commonly cut shortly after birth to age 15. In half the countries for which national figures were available in 20002010, most girls had been cut by age five.[4] Over 80 percent (of those cut) are cut before the age of five in Nigeria, Mali, Eritrea, Ghana and Mauritania.[96] The 1997 Demographic and Health Survey in Yemen found that 76 percent of girls had been cut within two weeks of birth.[97] The percentage is reversed in Somalia, Egypt, Chad and the Central African Republic, where over 80 percent (of those cut) are cut between five and 14.[96] Just as the type of FGM is often linked to ethnicity, so is the mean age. In Kenya, for example, the Kisi cut around age 10 and the Kamba at 16.[98]

A country's national prevalence often reflects a high sub-national prevalence among certain ethnicities, rather than a widespread practice.[99] In Iraq, for example, FGM is found mostly among the Kurds in Erbil (58 percent prevalence within age group 1549, as of 2011), Sulaymaniyah (54 percent) and Kirkuk (20 percent), giving the country a national prevalence of eight percent.[100] The practice is sometimes an ethnic marker, but it may differ along national lines. For example, in the northeastern regions of Ethiopia and Kenya, which share a border with Somalia, the Somali people practise FGM at around the same rate as they do in Somalia. But in Guinea all Fulani women responding to a survey in 2012 said they had experienced FGM,[102] against 12 percent of the Fulani in Chad, while in Nigeria the Fulani are the only large ethnic group in the country not to practise it.[103]

1996 Pulitzer Prize for Feature Photography

Stephanie Welsh, Newhouse News Service[104]

Dahabo Musa, a Somali woman, described infibulation in a 1988 poem as the "three feminine sorrows": the procedure itself, the wedding night when the woman is cut open, then childbirth when she is cut again. Despite the evident suffering, it is women who organize all forms of FGM.[r] Anthropologist Rose Oldfield Hayes wrote in 1975 that educated Sudanese men who did not want their daughters to be infibulated (preferring clitoridectomy) would find the girls had been sewn up after the grandmothers arranged a visit to relatives. Gerry Mackie has compared the practice to footbinding. Like FGM, footbinding was carried out on young girls, nearly universal where practised, tied to ideas about honour, chastity and appropriate marriage, and "supported and transmitted" by women.[s]

FGM practitioners see the procedures as marking not only ethnic boundaries but also gender difference. According to this view, male circumcision defeminizes men while FGM demasculinizes women.[114] Fuambai Ahmadu, an anthropologist and member of the Kono people of Sierra Leone, who in 1992 underwent clitoridectomy as an adult during a Sande society initiation, argued in 2000 that it is a male-centred assumption that the clitoris is important to female sexuality. African female symbolism revolves instead around the concept of the womb.[113] Infibulation draws on that idea of enclosure and fertility. "[G]enital cutting completes the social definition of a child's sex by eliminating external traces of androgyny," Janice Boddy wrote in 2007. "The female body is then covered, closed, and its productive blood bound within; the male body is unveiled, opened and exposed."[115]

In communities where infibulation is common, there is a preference for women's genitals to be smooth, dry and without odour, and both women and men may find the natural vulva repulsive. Some men seem to enjoy the effort of penetrating an infibulation.[117] The local preference for dry sex causes women to introduce substances into the vagina to reduce lubrication, including leaves, tree bark, toothpaste and Vicks menthol rub. The WHO includes this practice within Type IV FGM, because the added friction during intercourse can cause lacerations and increase the risk of infection.[119] Because of the smooth appearance of an infibulated vulva, there is also a belief that infibulation increases hygiene.

Common reasons for FGM cited by women in surveys are social acceptance, religion, hygiene, preservation of virginity, marriageability and enhancement of male sexual pleasure.[121] In a study in northern Sudan, published in 1983, only 17.4 percent of women opposed FGM (558 out of 3,210), and most preferred excision and infibulation over clitoridectomy. Attitudes are changing slowly. In Sudan in 2010, 42 percent of women who had heard of FGM said the practice should continue.[123] In several surveys since 2006, over 50 percent of women in Mali, Guinea, Sierra Leone, Somalia, Gambia, and Egypt supported FGM's continuance, while elsewhere in Africa, Iraq, and Yemen most said it should end, although in several countries only by a narrow margin.[124]

Against the argument that women willingly choose FGM for their daughters, UNICEF calls the practice a "self-enforcing social convention" to which families feel they must conform to avoid uncut daughters facing social exclusion.[126] Ellen Gruenbaum reported that, in Sudan in the 1970s, cut girls from an Arab ethnic group would mock uncut Zabarma girls with Ya, Ghalfa! ("Hey, unclean!"). The Zabarma girls would respond Ya, mutmura! (A mutmara was a storage pit for grain that was continually opened and closed, like an infibulated woman.) But despite throwing the insult back, the Zabarma girls would ask their mothers, "What's the matter? Don't we have razor blades like the Arabs?"

Because of poor access to information, and because circumcisers downplay the causal connection, women may not associate the health consequences with the procedure. Lala Bald, president of a women's association in Medina Cherif, a village in Senegal, told Mackie in 1998 that when girls fell ill or died, it was attributed to evil spirits. When informed of the causal relationship between FGM and ill health, Mackie wrote, the women broke down and wept. He argued that surveys taken before and after this sharing of information would show very different levels of support for FGM. The American non-profit group Tostan, founded by Molly Melching in 1991, introduced community-empowerment programs in several countries that focus on local democracy, literacy, and education about healthcare, giving women the tools to make their own decisions.[129] In 1997, using the Tostan program, Malicounda Bambara in Senegal became the first village to abandon FGM. By August 2019, 8,800 communities in eight countries had pledged to abandon FGM and child marriage.[t]

Surveys have shown a widespread belief, particularly in Mali, Mauritania, Guinea and Egypt, that FGM is a religious requirement.[132] Gruenbaum has argued that practitioners may not distinguish between religion, tradition, and chastity, making it difficult to interpret the data.[133] FGM's origins in northeastern Africa are pre-Islamic, but the practice became associated with Islam because of that religion's focus on female chastity and seclusion.[u] According to a 2013 UNICEF report, in 18 African countries at least 10 percent of Muslim females had experienced FGM, and in 13 of those countries, the figure rose to 5099 percent.[135] There is no mention of the practice in the Quran. It is praised in a few daf (weak) hadith (sayings attributed to Muhammad) as noble but not required,[137][v] although it is regarded as obligatory by the Shafi'i version of Sunni Islam. In 2007 the Al-Azhar Supreme Council of Islamic Research in Cairo ruled that FGM had "no basis in core Islamic law or any of its partial provisions".[139][w]

There is no mention of FGM in the Bible.[x] Christian missionaries in Africa were among the first to object to FGM, but Christian communities in Africa do practise it. In 2013 UNICEF identified 19 African countries in which at least 10 percent of Christian women and girls aged 15 to 49 had undergone FGM;[y] in Niger, 55 percent of Christian women and girls had experienced it, compared with two percent of their Muslim counterparts.[144] The only Jewish group known to have practised it are the Beta Israel of Ethiopia. Judaism requires male circumcision but does not allow FGM.[145] FGM is also practised by animist groups, particularly in Guinea and Mali.[146]

Spell 1117

But if a man wants to know how to live, he should recite it [a magical spell] every day, after his flesh has been rubbed with the b3d [unknown substance] of an uncircumcised girl ['m't] and the flakes of skin [nft] of an uncircumcised bald man.

From an Egyptian sarcophagus, c.19911786BCE

The practice's origins are unknown. Gerry Mackie has suggested that, because FGM's east-west, north-south distribution in Africa meets in Sudan, infibulation may have begun there with the Meroite civilization (c.800 BCE c.350 CE), before the rise of Islam, to increase confidence in paternity. According to historian Mary Knight, Spell 1117 (c.19911786 BCE) of the Ancient Egyptian Coffin Texts may refer in hieroglyphs to an uncircumcised girl ('m't):

The spell was found on the sarcophagus of Sit-hedjhotep, now in the Egyptian Museum, and dates to Egypt's Middle Kingdom.[z] (Paul F. O'Rourke argues that 'm't probably refers instead to a menstruating woman.) The proposed circumcision of an Egyptian girl, Tathemis, is also mentioned on a Greek papyrus, from 163BCE, in the British Museum: "Sometime after this, Nephoris [Tathemis's mother] defrauded me, being anxious that it was time for Tathemis to be circumcised, as is the custom among the Egyptians."[aa]

The examination of mummies has shown no evidence of FGM. Citing the Australian pathologist Grafton Elliot Smith, who examined hundreds of mummies in the early 20th century, Knight writes that the genital area may resemble Type III because during mummification the skin of the outer labia was pulled toward the anus to cover the pudendal cleft, possibly to prevent sexual violation. It was similarly not possible to determine whether Types I or II had been performed, because soft tissues had deteriorated or been removed by the embalmers.

The Greek geographer Strabo (c. 64 BCE c. 23 CE) wrote about FGM after visiting Egypt around 25 BCE: "This is one of the customs most zealously pursued by them [the Egyptians]: to raise every child that is born and to circumcise [peritemnein] the males and excise [ektemnein] the females..."[152][ab][ac] Philo of Alexandria (c. 20 BCE 50 CE) also made reference to it: "the Egyptians by the custom of their country circumcise the marriageable youth and maid in the fourteenth (year) of their age, when the male begins to get seed, and the female to have a menstrual flow." It is mentioned briefly in a work attributed to the Greek physician Galen (129 c.200 CE): "When [the clitoris] sticks out to a great extent in their young women, Egyptians consider it appropriate to cut it out."[ad] Another Greek physician, Atius of Amida (mid-5th to mid-6th century CE), offered more detail in book 16 of his Sixteen Books on Medicine, citing the physician Philomenes. The procedure was performed in case the clitoris, or nymph, grew too large or triggered sexual desire when rubbing against clothing. "On this account, it seemed proper to the Egyptians to remove it before it became greatly enlarged," Atius wrote, "especially at that time when the girls were about to be married":

The surgery is performed in this way: Have the girl sit on a chair while a muscled young man standing behind her places his arms below the girl's thighs. Have him separate and steady her legs and whole body. Standing in front and taking hold of the clitoris with a broad-mouthed forceps in his left hand, the surgeon stretches it outward, while with the right hand, he cuts it off at the point next to the pincers of the forceps. It is proper to let a length remain from that cut off, about the size of the membrane that's between the nostrils, so as to take away the excess material only; as I have said, the part to be removed is at that point just above the pincers of the forceps. Because the clitoris is a skinlike structure and stretches out excessively, do not cut off too much, as a urinary fistula may result from cutting such large growths too deeply.

The genital area was then cleaned with a sponge, frankincense powder and wine or cold water, and wrapped in linen bandages dipped in vinegar, until the seventh day when calamine, rose petals, date pits, or a "genital powder made from baked clay" might be applied.

Whatever the practice's origins, infibulation became linked to slavery. Mackie cites the Portuguese missionary Joo dos Santos, who in 1609 wrote of a group near Mogadishu who had a "custome to sew up their Females, especially their slaves being young to make them unable for conception, which makes these slaves sell dearer, both for their chastitie, and for better confidence which their Masters put in them". Thus, Mackie argues, a "practice associated with shameful female slavery came to stand for honor".

Gynaecologists in 19th-century Europe and the United States removed the clitoris to treat insanity and masturbation. A British doctor, Robert Thomas, suggested clitoridectomy as a cure for nymphomania in 1813.[162] In 1825 The Lancet described a clitoridectomy performed in 1822 in Berlin by Karl Ferdinand von Graefe on a 15-year-old girl who was masturbating excessively.[163]

Isaac Baker Brown, an English gynaecologist, president of the Medical Society of London and co-founder in 1845 of St. Mary's Hospital, believed that masturbation, or "unnatural irritation" of the clitoris, caused hysteria, spinal irritation, fits, idiocy, mania and death. He therefore "set to work to remove the clitoris whenever he had the opportunity of doing so", according to his obituary.[160] Brown performed several clitoridectomies between 1859 and 1866.[160] In the United States, J. Marion Sims followed Brown's work and in 1862 slit the neck of a woman's uterus and amputated her clitoris, "for the relief of the nervous or hysterical condition as recommended by Baker Brown". When Brown published his views in On the Curability of Certain Forms of Insanity, Epilepsy, Catalepsy, and Hysteria in Females (1866), doctors in London accused him of quackery and expelled him from the Obstetrical Society.[166]

Later in the 19th century, A. J. Bloch, a surgeon in New Orleans, removed the clitoris of a two-year-old girl who was reportedly masturbating. According to a 1985 paper in the Obstetrical & Gynecological Survey, clitoridectomy was performed in the United States into the 1960s to treat hysteria, erotomania and lesbianism.[168] From the mid-1950s, James C. Burt, a gynaecologist in Dayton, Ohio, performed non-standard repairs of episiotomies after childbirth, adding more stitches to make the vaginal opening smaller. From 1966 until 1989, he performed "love surgery" by cutting women's pubococcygeus muscle, repositioning the vagina and urethra, and removing the clitoral hood, thereby making their genital area more appropriate, in his view, for intercourse in the missionary position. "Women are structurally inadequate for intercourse," he wrote; he said he would turn them into "horny little mice".[170] In the 1960s and 1970s he performed these procedures without consent while repairing episiotomies and performing hysterectomies and other surgery; he said he had performed a variation of them on 4,000 women by 1975. Following complaints, he was required in 1989 to stop practicing medicine in the United States.[171]

Muthirigu

Little knives in their sheathsThat they may fight with the church,The time has come.Elders (of the church)When Kenyatta comesYou will be given women's clothesAnd you will have to cook him his food.

From the Muthirigu (1929), Kikuyu dance-songs against church opposition to FGM[172]

Protestant missionaries in British East Africa (present-day Kenya) began campaigning against FGM in the early 20th century, when Dr. John Arthur joined the Church of Scotland Mission (CSM) in Kikuyu. An important ethnic marker, the practice was known by the Kikuyu, the country's main ethnic group, as irua for both girls and boys. It involved excision (Type II) for girls and removal of the foreskin for boys. Unexcised Kikuyu women (irugu) were outcasts.[173]

Jomo Kenyatta, general secretary of the Kikuyu Central Association and later Kenya's first prime minister, wrote in 1938 that, for the Kikuyu, the institution of FGM was the "conditio sine qua non of the whole teaching of tribal law, religion and morality". No proper Kikuyu man or woman would marry or have sexual relations with someone who was not circumcised, he wrote. A woman's responsibilities toward the tribe began with her initiation. Her age and place within tribal history was traced to that day, and the group of girls with whom she was cut was named according to current events, an oral tradition that allowed the Kikuyu to track people and events going back hundreds of years.

Beginning with the CSM in 1925, several missionary churches declared that FGM was prohibited for African Christians; the CSM announced that Africans practising it would be excommunicated, which resulted in hundreds leaving or being expelled. In 1929 the Kenya Missionary Council began referring to FGM as the "sexual mutilation of women", and a person's stance toward the practice became a test of loyalty, either to the Christian churches or to the Kikuyu Central Association.[176] The stand-off turned FGM into a focal point of the Kenyan independence movement; the 19291931 period is known in the country's historiography as the female circumcision controversy.[177] When Hulda Stumpf, an American missionary who opposed FGM in the girls' school she helped to run, was murdered in 1930, Edward Grigg, the governor of Kenya, told the British Colonial Office that the killer had tried to circumcise her.[178]

There was some opposition from Kenyan women themselves. At the mission in Tumutumu, Karatina, where Marion Scott Stevenson worked, a group calling themselves Ngo ya Tuiritu ("Shield of Young Girls"), the membership of which included Raheli Warigia (mother of Gakaara wa Wanja), wrote to the Local Native Council of South Nyeri on 25 December 1931: "[W]e of the Ngo ya Tuiritu heard that there are men who talk of female circumcision, and we get astonished because they (men) do not give birth and feel the pain and even some die and even others become infertile, and the main cause is circumcision. Because of that the issue of circumcision should not be forced. People are caught like sheep; one should be allowed to cut her own way of either agreeing to be circumcised or not without being dictated on one's own body."[179]

Elsewhere, support for the practice from women was strong. In 1956 in Meru, eastern Kenya, when the council of male elders (the Njuri Nchecke) announced a ban on FGM in 1956, thousands of girls cut each other's genitals with razor blades over the next three years as a symbol of defiance. The movement came to be known as Ngaitana ("I will circumcise myself"), because to avoid naming their friends the girls said they had cut themselves. Historian Lynn Thomas described the episode as significant in the history of FGM because it made clear that its victims were also its perpetrators.[180] FGM was eventually outlawed in Kenya in 2001, although the practice continued, reportedly driven by older women.[181]

1920s1980s timeline

One of the earliest campaigns against FGM began in Egypt in the 1920s, when the Egyptian Doctors' Society called for a ban.[ae] There was a parallel campaign in Sudan, run by religious leaders and British women. Infibulation was banned there in 1946, but the law was unpopular and barely enforced.[af] The Egyptian government banned infibulation in state-run hospitals in 1959, but allowed partial clitoridectomy if parents requested it. (Egypt banned FGM entirely in 2007.)

In 1959, the UN asked the WHO to investigate FGM, but the latter responded that it was not a medical matter. Feminists took up the issue throughout the 1970s. The Egyptian physician and feminist Nawal El Saadawi criticized FGM in her book Women and Sex (1972); the book was banned in Egypt and El Saadawi lost her job as director general of public health.[189] She followed up with a chapter, "The Circumcision of Girls", in her book The Hidden Face of Eve: Women in the Arab World (1980), which described her own clitoridectomy when she was six years old:

I did not know what they had cut off from my body, and I did not try to find out. I just wept, and called out to my mother for help. But the worst shock of all was when I looked around and found her standing by my side. Yes, it was her, I could not be mistaken, in flesh and blood, right in the midst of these strangers, talking to them and smiling at them, as though they had not participated in slaughtering her daughter just a few moments ago.

In 1975, Rose Oldfield Hayes, an American social scientist, became the first female academic to publish a detailed account of FGM, aided by her ability to discuss it directly with women in Sudan. Her article in American Ethnologist called it "female genital mutilation", rather than female circumcision, and brought it to wider academic attention. Edna Adan Ismail, who worked at the time for the Somalia Ministry of Health, discussed the health consequences of FGM in 1977 with the Somali Women's Democratic Organization.[193] Two years later Fran Hosken, an Austria-American feminist, published The Hosken Report: Genital and Sexual Mutilation of Females (1979), the first to offer global figures. She estimated that 110,529,000 women in 20 African countries had experienced FGM. The figures were speculative but consistent with later surveys. Describing FGM as a "training ground for male violence", Hosken accused female practitioners of "participating in the destruction of their own kind". The language caused a rift between Western and African feminists; African women boycotted a session featuring Hosken during the UN's Mid-Decade Conference on Women in Copenhagen in July 1980.[197]

In 1979, the WHO held a seminar, "Traditional Practices Affecting the Health of Women and Children", in Khartoum, Sudan, and in 1981, also in Khartoum, 150 academics and activists signed a pledge to fight FGM after a workshop held by the Babiker Badri Scientific Association for Women's Studies (BBSAWS), "Female Circumcision Mutilates and Endangers Women Combat it!" Another BBSAWS workshop in 1984 invited the international community to write a joint statement for the United Nations.[198] It recommended that the "goal of all African women" should be the eradication of FGM and that, to sever the link between FGM and religion, clitoridectomy should no longer be referred to as sunna.[199]

The Inter-African Committee on Traditional Practices Affecting the Health of Women and Children, founded in 1984 in Dakar, Senegal, called for an end to the practice, as did the UN's World Conference on Human Rights in Vienna in 1993. The conference listed FGM as a form of violence against women, marking it as a human-rights violation, rather than a medical issue.[200] Throughout the 1990s and 2000s governments in Africa and the Middle East passed legislation banning or restricting FGM. In 2003 the African Union ratified the Maputo Protocol on the rights of women, which supported the elimination of FGM.[201] By 2015 laws restricting FGM had been passed in at least 23 of the 27 African countries in which it is concentrated, although several fell short of a ban.[ag]

In December 1993, the United Nations General Assembly included FGM in resolution 48/104, the Declaration on the Elimination of Violence Against Women, and from 2003 sponsored International Day of Zero Tolerance for Female Genital Mutilation, held every 6 February.[205][206] UNICEF began in 2003 to promote an evidence-based social norms approach, using ideas from game theory about how communities reach decisions about FGM, and building on the work of Gerry Mackie on the demise of footbinding in China.[207] In 2005 the UNICEF Innocenti Research Centre in Florence published its first report on FGM.[27] UNFPA and UNICEF launched a joint program in Africa in 2007 to reduce FGM by 40 percent within the 015 age group and eliminate it from at least one country by 2012, goals that were not met and which they later described as unrealistic.[208][ah] In 2008 several UN bodies recognized FGM as a human-rights violation,[210] and in 2010 the UN called upon healthcare providers to stop carrying out the procedures, including reinfibulation after childbirth and symbolic nicking.[10] In 2012 the General Assembly passed resolution 67/146, "Intensifying global efforts for the elimination of female genital mutilations".[211]

According to UNICEF, 97% of women in Guinea and 75% in Gambia, Burkina Faso, Mali, and Sierra Leone undergo FGM. It is practiced in 30 countries in Africa, the Middle East, and Asia, as well as among migrants from those countries.[212]

Immigration spread the practice to Australia, New Zealand, Europe and North America, all of which outlawed it entirely or restricted it to consenting adults.[213] Sweden outlawed FGM in 1982 with the Act Prohibiting the Genital Mutilation of Women, the first Western country to do so.[214] Several former colonial powers, including Belgium, Britain, France and the Netherlands, introduced new laws or made clear that it was covered by existing legislation. As of 2013[update] legislation banning FGM had been passed in 33 countries outside Africa and the Middle East.[202]

In the United States an estimated 513,000 women and girls had experienced FGM or were at risk as of 2012.[216][217][ai] A Nigerian woman successfully contested deportation in March 1994, asking for "cultural asylum" on the grounds that her young daughters (who were American citizens) might be cut if she brought them to Nigeria,[219][220][221] and in 1996 Fauziya Kasinga from Togo became the first to be officially granted asylum to escape FGM.[222] In 1996 the Federal Prohibition of Female Genital Mutilation Act made it illegal to perform FGM on minors for non-medical reasons, and in 2013 the Transport for Female Genital Mutilation Act prohibited transporting a minor out of the country for the purpose of FGM.[216]:2 The first FGM conviction in the US was in 2006, when Khalid Adem, who had emigrated from Ethiopia, was sentenced to ten years for aggravated battery and cruelty to children after severing his two-year-old daughter's clitoris with a pair of scissors.[223] A federal judge ruled in 2018 that the 1996 Act was unconstitutional, arguing that FGM is a "local criminal activity" that should be regulated by states, not by Congress; he made his ruling during a case against members of the Dawoodi Bohra community in Michigan accused of carrying out FGM.[224] Twenty-four states had legislation banning FGM as of 2016.[216]:2 The American Academy of Pediatrics opposes all forms of the practice, including pricking the clitoral skin.[aj]

Canada recognized FGM as a form of persecution in July 1994, when it granted refugee status to Khadra Hassan Farah, who had fled Somalia to avoid her daughter being cut.[226] In 1997 section 268 of its Criminal Code was amended to ban FGM, except where "the person is at least eighteen years of age and there is no resulting bodily harm".[227][202] As of July2017[update] there had been no prosecutions. Canadian officials have expressed concern that a few thousand Canadian girls are at risk of "vacation cutting", whereby girls are taken overseas to undergo the procedure, but as of 2017 there were no firm figures.[228]

According to the European Parliament, 500,000 women in Europe had undergone FGM as of March2009[update]. In France up to 30,000 women were thought to have experienced it as of 1995. According to Colette Gallard, a family-planning counsellor, when FGM was first encountered in France, the reaction was that Westerners ought not to intervene. It took the deaths of two girls in 1982, one of them three months old, for that attitude to change.[231] In 1991 a French court ruled that the Convention Relating to the Status of Refugees offered protection to FGM victims; the decision followed an asylum application from Aminata Diop, who fled an FGM procedure in Mali.[232] The practice is outlawed by several provisions of France's penal code that address bodily harm causing permanent mutilation or torture.[233][231] The first civil suit was in 1982, and the first criminal prosecution in 1993.[226] In 1999 a woman was given an eight-year sentence for having performed FGM on 48 girls.[234] By 2014 over 100 parents and two practitioners had been prosecuted in over 40 criminal cases.[231]

Around 137,000 women and girls living in England and Wales were born in countries where FGM is practised, as of 2011.[235] Performing FGM on children or adults was outlawed under the Prohibition of Female Circumcision Act 1985.[236] This was replaced by the Female Genital Mutilation Act 2003 and Prohibition of Female Genital Mutilation (Scotland) Act 2005, which added a prohibition on arranging FGM outside the country for British citizens or permanent residents.[237][ak] The United Nations Committee on the Elimination of Discrimination against Women (CEDAW) asked the government in July 2013 to "ensure the full implementation of its legislation on FGM".[239] The first charges were brought in 2014 against a physician and another man; the physician had stitched an infibulated woman after opening her for childbirth. Both men were acquitted in 2015.[240]

Anthropologists have accused FGM eradicationists of cultural colonialism, and have been criticized in turn for their moral relativism and failure to defend the idea of universal human rights. According to critics of the eradicationist position, the biological reductionism of the opposition to FGM, and the failure to appreciate FGM's cultural context, serves to "other" practitioners and undermine their agencyin particular when parents are referred to as "mutilators".

Africans who object to the tone of FGM opposition risk appearing to defend the practice. The feminist theorist Obioma Nnaemeka, herself strongly opposed to FGM, argued in 2005 that renaming the practice female genital mutilation had introduced "a subtext of barbaric African and Muslim cultures and the West's relevance (even indispensability) in purging [it]". According to Ugandan law professor Sylvia Tamale, the early Western opposition to FGM stemmed from a Judeo-Christian judgment that African sexual and family practices, including not only FGM but also dry sex, polygyny, bride price and levirate marriage, required correction. African feminists "take strong exception to the imperialist, racist and dehumanising infantilization of African women", she wrote in 2011. Commentators highlight the voyeurism in the treatment of women's bodies as exhibits. Examples include images of women's vulvas after FGM or girls undergoing the procedure. The 1996 Pulitzer-prize-winning photographs of a 16-year-old Kenyan girl experiencing FGM were published by 12 American newspapers, without her consent either to be photographed or to have the images published.[247]

The debate has highlighted a tension between anthropology and feminism, with the former's focus on tolerance and the latter's on equal rights for women. According to the anthropologist Christine Walley, a common position in anti-FGM literature has been to present African women as victims of false consciousness participating in their own oppression, a position promoted by feminists in the 1970s and 1980s, including Fran Hosken, Mary Daly and Hanny Lightfoot-Klein. It prompted the French Association of Anthropologists to issue a statement in 1981, at the height of the early debates, that "a certain feminism resuscitates (today) the moralistic arrogance of yesterday's colonialism".

Nnaemeka argues that the crucial question, broader than FGM, is why the female body is subjected to so much "abuse and indignity", including in the West. Several authors have drawn a parallel between FGM and cosmetic procedures.[250] Ronn Conroy of the Royal College of Surgeons in Ireland wrote in 2006 that cosmetic genital procedures were "driving the advance" of FGM by encouraging women to see natural variations as defects. Anthropologist Fadwa El Guindi compared FGM to breast enhancement, in which the maternal function of the breast becomes secondary to men's sexual pleasure. Benote Groult, the French feminist, made a similar point in 1975, citing FGM and cosmetic surgery as sexist and patriarchal. Against this, the medical anthropologist Carla Obermeyer argued in 1999 that FGM may be conducive to a subject's social well-being in the same way that rhinoplasty and male circumcision are.[254] Despite the 2007 ban in Egypt, Egyptian women wanting FGM for their daughters seek amalyet tajmeel (cosmetic surgery) to remove what they see as excess genital tissue.[255]

Cosmetic procedures such as labiaplasty and clitoral hood reduction do fall within the WHO's definition of FGM, which aims to avoid loopholes, but the WHO notes that these elective practices are generally not regarded as FGM.[al] Some legislation banning FGM, such as in Canada and the US, covers minors only, but several countries, including Sweden and the UK, have banned it regardless of consent. Sweden, for example, has banned operations "on the outer female sexual organs with a view to mutilating them or bringing about some other permanent change in them, regardless of whether or not consent has been given for the operation".[214] Gynaecologist Birgitta Essn and anthropologist Sara Johnsdotter argue that the law seems to distinguish between Western and African genitals, and deems only African women (such as those seeking reinfibulation after childbirth) unfit to make their own decisions.[257]

The philosopher Martha Nussbaum argues that a key concern with FGM is that it is mostly conducted on children using physical force. The distinction between social pressure and physical force is morally and legally salient, comparable to the distinction between seduction and rape. She argues further that the literacy of women in practising countries is generally poorer than in developed nations, which reduces their ability to make informed choices.[259]

Several commentators maintain that children's rights are violated not only by FGM but also by the genital alteration of intersex children, who are born with anomalies that physicians choose to correct.[260] Arguments have been made that non-therapeutic male circumcision, practised by Muslims, Jews and some Christian groups, also violates children's rights. Globally about 30 percent of males over 15 are circumcised; of these, about two-thirds are Muslim.[261] An American Academy of Pediatrics circumcision task force issued a policy statement in 2012 that the health benefits of male circumcision outweigh the risks; they recommended that it be carried out, if it is performed, by "trained and competent practitioners... using sterile techniques and effective pain management".[262] The statement met with protests from a group of 38 doctors in Europe, who accused the task force of "cultural bias".[263] At least half the male population of the United States is circumcised,[262] while most men in Europe are not.[263]

WHO (2008): "[There is a] common tendency to describe Type I as removal of the prepuce, whereas this has not been documented as a traditional form of female genital mutilation. However, in some countries, medicalized female genital mutilation can include removal of the prepuce only (Type Ia) (Thabet and Thabet, 2003), but this form appears to be relatively rare (Satti et al., 2006). Almost all known forms of female genital mutilation that remove tissue from the clitoris also cut all or part of the clitoral glans itself."[39]

Pam Belluck (The New York Times, 10 June 2017): "The focus on the Dawoodi Bohra, a sect of about 1.2 million based in western India, with clusters in the United States, Pakistan and elsewhere, is spurring Bohra women to describe their experiences publicly. Some are doing so for the first time, defying the sect's historic secrecy about cutting and taking a risk that they or relatives will be ostracized."[86]

Bettina Shell-Duncan (2015): "[W]hen you talk to people on the ground, you also hear people talking about the idea that it's women's business. As in, it's for women to decide this. If we look at the data across Africa, the support for the practice is stronger among women than among men."

Book XVI, chapter 4, 16.4.9: "And then to the Harbour of Antiphilus, and, above this, to the Creophagi [meat-eaters], of whom the males have their sexual glands mutilated [kolobos] and the women are excised [ektemnein] in the Jewish fashion."

Donaldson James, Susan (13 December 2012). "Ohio Woman Still Scarred By 'Love' Doctor's Sex Surgery". ABC News.

Canada: Section 268, Criminal Code, Justice Laws website, Government of Canada.

"In re Fauziya KASINGA, file A73 476 695", U.S. Department of Justice, Executive Office for Immigration Review, decided 13 June 1996.

Pam Belluck, "Group Backs Ritual 'Nick' as Female Circumcision Option", The New York Times, 6 May 2010.

For an early article on FGM in the UK, see Black & Debelle 1995

Gregorio, I. W. (26 April 2017). "Should Surgeons Perform Irreversible Genital Surgery on Children?". Newsweek.

Freedman, Andrew L. (May 2016). "The Circumcision Debate: Beyond Benefits and Risks". Pediatrics. 137 (5): e20160594. doi:10.1542/peds.2016-0594. PMID27244839.

American Academy of Pediatrics Task Force on Circumcision (April 2013). "Cultural Bias and Circumcision: The AAP Task Force on Circumcision Responds". Pediatrics. 131 (4): 8014. doi:10.1542/peds.2013-0081. PMID23509171.

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Female genital mutilation - Wikipedia

Recommendation and review posted by Bethany Smith

Scientific fields have not only overlooked female researchers, but have also overlooked research into female biology, both of humans and animals

On International Womens Day, people across the world are taking part in Wikipedia edit-a-thons to address gender bias in the online encyclopedias biographies.

Currently, only about 17 per cent of Wikipedias biography pages are about women. Many of the edit-a-thons will specifically focus on women in STEM.

Scientific fields have not only overlooked female researchers, but have also overlooked research into female biology, both of humans and animals. For centuries, our understanding of the natural world has been shaped by a predominately male perspective. But this is changing, thanks to pioneering biologists.

Male and female behaviours

Evolutionary biologist Sara Lipshutz, for example, studies mechanisms underlying sex-role reversal in the jacana, a tropical wading bird. Jacana females aggressively compete for mates while the males provide parental care.

Molecular biologist Mariana Wolfner studies how female insects genetics influence which males sperm (of the many she mates with) are chosen to fertilise the ovum. Zoologist Kay Holekamp studies how reproduction is affected by both competition and co-operation in female hyenas.

Active male, passive female?

The inclusion of women in clinical trials and female animals in pre-clinical trials has received a lot of attention in recent years, but our understanding of the natural world has also been influenced by a male-dominated culture. And this problem dates back to antiquity.

Lets go back to Aristotle, says Virginia Hayssen, a mammologist at Smith College in Northampton, Massachusetts. Aristotle believed that during conception, the father contributed form in other words, the immutable essence of a thing and the mother provided the receptacle in which this form developed.

Although we understand the process better now, we havent really gotten past that idea that the male is active and the female is passive, says Hayssen.

Traditionally, she says, conception is presented as the sperms race to the ovum. But the female reproductive tract is actually hugely influential in transporting the sperm to the ovum and in determining which sperm is the winner.

Many biologists are coming to realise that weve missed a lot by having such a narrow focus. We cant tell the whole story with our science if were imposing our biases on an animal system, says Lipshutz.

Without fully understanding the male and female sides of reproduction, we wont be able to understand how species evolve, since reproduction is a central component of evolution. Lipshutz also notes that understanding more about how females communicate, compete and choose mates could have important implications for conservation.

So, is the field as a whole finally undergoing a cultural shift to value female-focused research as much as male-focused research? Some say no.

I would say that the male perspective is as dominant as it ever was, says Hayssen, who was a co-organiser of a symposium on reproduction from a female perspective at the Society for Integrative and Comparative Biology annual meeting, held in January 2020.

But others have a slightly more optimistic outlook. While acknowledging that there is still a long way to go, scientists including Lipshutz and Teri Orr, an evolutionary ecologist at New Mexico State University in Las Cruces and co-organiser of the symposium, say they feel that progress is being made.

Some of these advancements have been at least partially driven by improvements in technology.

Orr says one example of this is red-winged blackbird reproduction. For a long time, biologists thought that a male maintained a territory with many females who mated exclusively with this male. It was only once DNA testing became available that scientists were able to run paternity tests on the baby birds and determine that many had not been fathered by the male who was in charge of the territory, showing that females were behaving in unexpected ways.

Read more: How genetic testing is helping scientists save animals from disease and illegal hunting

Inclusion and representation

But Lipshutz and Orr say that many of these changes have been driven by the culture of the field as well. After all, new technologies wouldnt have made any difference if scientists had used them to answer the same old questions about the biology of males.

I think it has to do with representation, says Lipshutz. There are many models of how women are still not getting equal representation in academia, but I do think its much better than it was 20 years ago. And so I think it makes sense that our perspectives are often shaped by that diversity.

Orr says that she sees a big generational difference as well. She says younger generations of academics realize that these are important issues that need to be addressed.

Nevertheless, theres still much that needs to be done, both inside and outside academia. For one thing, theres still an immense amount of research that must to be carried out before our understanding of female biology catches up with our understanding of male biology.

Orr, Lipshutz and Hayssen also stress the importance of education and mentorship in helping to address these issues. Regarding the importance of female biology, Orr says: The question is how do we bring that back into the classroom? Because thats where stereotypes are challenged, thats where people really learn the material. In an attempt to improve education about females, Orr and Hayssen have written a textbook, Reproduction in Mammals: The Female Perspective.

Hayssen notes that the media has an important role to play as well. What happens next, she says, depends on whether all this still gets shoved under the rug or whether [journalists] carry the torch forward and get other people interested in it.

But many biologists are hopeful about what the future will bring.

Younger folks in the field are really passionate, says Orr. I do think some big changes are definitely around the corner and Im very excited to see what happens.

Hannah Thomasy, Global Journalism Fellow, Dalla Lana School of Public Health, University of Toronto

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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International Women's Day: Female biologists bring much-needed perspective to science - Down To Earth Magazine

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For many dog owners, thunderstorms are a source of angst, a walk to the dog park can be a fraught experience, and New Years celebrations are particularly stressful. According to a new study of thousands of pet dogs, anxiety and fear-related behavior problems are widespread. Certain breeds are particularly sensitive to loud noises or being left alone. Other breeds may engage in compulsive behaviors such as biting themselves or urinating, suggesting a genetic component to the activity.

James Serpell, an ethologist at the University of Pennsylvania, who was not involved in the study, says that the problem stems from owners failing to properly socialize their dogs. Many canines rescued from shelters may have been inadequately trained when they were young, and the problem is compounded when new owners are overly cautious with them. Its a sort of helicopter-parenting concept applied to dogs, he says. Animals are not getting enough exposure to normal social interactions, play behavior and roughhousing with other dogs. Thats asking for trouble.

In the study, Hannes Lohi, a geneticist at the University of Helsinki, and his colleagues surveyed Finnish owners of 13,715 pet dogsor nearly 2 percent of the total population of the animals in Finland. The dog owners responded to questions about the dogs age, socialization,and behavior around humans and unfamiliar dogs and in new environments. The researchers published their results on Thursday in Scientific Reports. About 72 percent of the dogs exhibited problematic behaviors such as aggression or fearfulness. Meanwhile 32 percent of them were afraid of noises, which was the most common form of anxiety, and about one quarter were fearful of fireworks in particular. Sensitivity to loud noises increased with age. Younger dogs tended to damage property or urinate when left alone more often than older animals did. And male dogs were more hyperactive and aggressive than female ones.

Lohi also found that dog breeds had very different behavioral profiles.Romagnolos were most likely to be afraid of thunder, and Labrador retrievers were least likely to be. More miniature schnauzers, and fewer Labradors, were aggressive toward strangers than other dogs. Mixed breeds had the highest levels of inattentiveness, a trait shown in dogs considered hard to train. The breed specificity of these traits suggests that genetics plays a role in their development, Lohi says.

In a study he co-authored in January 2019 in Translational Psychiatry, Lohi and his colleagues found a gene in German shepherds linked to age-dependent hearing defects and anxiety. But it is not really known whether this is a [physical] or psychiatric issue, he says.

The new study also examined comorbidities, or different conditions present in the same animal. Fear and noise sensitivity were common comorbidities, although this may have been because the sample included so many dogs that exhibited each trait. And separation-related anxiety behavior was more common among dogs that were sensitive to noise. Serpell is skeptical about calling these observations comorbidities, however. The term tends to imply that a pathology is involved, but these are normal dog behaviors, he explains. Instead, Serpell says, I would expect there to be an association between fear and aggression. A lot of aggression in dogs is triggered by fear.

Nicholas Dodman, a veterinary behaviorist at Tufts University and chief scientist at the Center for Canine Behavior Studies, who was not involved in Lohis analysis, published a similar paper on behavioral problems in the July-August 2019 issue of theJournal of Veterinary Behavior. There are some inherent pitfalls to the questionnaire-based approach, which apply to our study as well, Dodman says. Surveying owners about their dogs behavior assumes they are vigilant witnesses, he says. And seeing a certain behavior in a canine, such as the animal scratching itself, does not explain why it exhibits that behavior. The observation does not allow an inference to be made, for instance, that the dog has developed a compulsive disorder.

Human selection for traits such as herding or guarding may have predisposed some breeds to engage in compulsive behaviors, Lohi says. In the new study, border collies, which were bred to herd livestock, were more prone to chasing lights and shadows, whereas Staffordshire bull terriers were the most likely to chase their own tails, an impulsive behavior that suggests a genetic defect has been enriched in that breed, he adds.

Breeding programs can gradually eliminate such traits by avoiding dogs with behavioral problems that have a genetic component, Lohi says. But selective breeding for any trait has risks, says Anindita Bhadra, a behavioral biologist at the Indian Institute of Science Education and Research, who also was not part of the new study. Attempting to breed anxiety-free dogs could bring about other problems, she says. We know that most complex traits are multigenic, and artificial selection often leads to inadvertent changes while selecting for a set of traits, Bhadra adds.

Lohi says the next step in understanding these behavioral issues is to tease apart what environmental, lifestyle and genetic risk factors predispose dogs to them. The overarching goal of the research is ultimately to understand how useful dogs can be to model human anxiety and how much they share similar risk or protective factors, he says. Eventually, this could help to advance the health and welfare across species.

Read more:
Three Fourths of Dogs Are Angst-Ridden--and Owners May Be Partly to Blame - Scientific American

Recommendation and review posted by Bethany Smith

Painless non surgical skin tightening procedures are now available and very popular for people who don't want to go through surgery in order to look better. Call LifeGaines in Boca Raton for more information about "Thread Lifts."

Boca Raton, Florida--(Newsfile Corp. - March 5, 2020) - Thread Lifts are a simple, painless procedure used for skin tightening on the face, neck, or anywhere else on the body. As popular and effective as Botox is, it simply doesn't have the ability to lift the skin. In the past, there hasn't been a great way to produce lifting results without surgery.

Call LifeGaines to inquire about this new method of skin tightening in the South Florida area. Call 561-295-9007.

To view an enhanced version of this image, please visit:https://orders.newsfilecorp.com/files/6848/53186_lifegaines_orig.jpg

Non-surgical aesthetics are in high demand and ThreadLifts, new to the United States, have the ability to produce skin that is instantly lifted and tightened.

This procedure uses no cuts or incisions, only injections. Threads are needles that are pre-loaded with PDO thread. The whole needle is inserted in the tissue at the sub-dermal level, along the surface of the skin and then the needle is pulled out. Threads can be used nearly anywhere on the body, but they are especially effective on the neck and jawline.

What is PDO?

Polydioxanone (PDO) sutures have been used for surgical procedures for many decades. It is one of the safest materials to implant in the body. PDO is completely dissolvable and your skin fully absorbs it within 4 to 6 months, leaving no scar tissue behind. This is especially effective when it's used together with chemical peels, Botox, and fillers to effect a patient's entire facial structure, remove sunspots and other conditions.

It is a great way to rejuvenate and restore youthful contours to brows, cheeks, jowls and the neck area. They are also effective on the breasts, buttocks and upper arms, areas that are prone to sagging due to weight loss, aging, pregnancy and childbirth or poor muscle tone.

Thread Lifts are a great way to rejuvenate and restore youthful contours to brows, cheeks, jowls and the neck area. Results from threads generally last between 12 months to several years depending on the area that has been treated, how many threads are used and what kinds of threads are used in each needle.

Amy Steffey, is a Licensed Nurse Practitioner with LifeGaines Medical and Aesthetics, and with Thread Liftsprocedure, she helps Boca Raton residents regain their confidence with rejuvenating procedures and body contouring.

Amy Steffey works at LifeGaines, which is one of the most highly respected Age Management Medical teams in South Florida. Age Management Medicine pioneer Dr. Richard Gaines is the founder of LifeGaines, and he has years of experience specializing in Hormone Replacement Therapy, Sexual Wellness, Platelet-rich Plasma, Stem Cells, Aesthetics, and Advanced Age Management protocols.

LifeGaines is located at 3785 N Federal Hwy #150, Boca Raton, FL 33431.

Call 561-295-9007 Today to Schedule a Consultation with Amy Steffey at LifeGaines Medical & Aesthetics Center in Boca Raton.

Related Images

people-who-dont-want-to-do-surgery.jpg People who don't want to do surgery could consider a non-surgical way of tightening skin. Call LifeGaines to inquire about this new method of skin tightening in the South Florida area. Call 561-295-9007.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/53186

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Non Surgical Aesthetics Are in High Demand, So Thread Lifts Are a New Way to Achieve Instant Skin Tightening - Yahoo Finance

Recommendation and review posted by Bethany Smith

1 Molecular missing link: Research explains why some creams cause a skin rash

Allergic skin reactions can be caused by many different chemical compounds found in skincare creams, cosmetics and other topical consumer products, but how they trigger the reaction has remained somewhat mysteriousuntil now.

New research that suggests the way some chemicals displace natural fat-like molecules known as lipids in skin cells may explain how many common ingredients trigger allergic contact dermatitis.

The breakthrough could help stem soaring cases of rashes, lumps, blisters, itchy eyes and facial swellings. It has been dubbed the molecular missing link because it might have brought a new way to treat the condition.

Currently, the only way to stop allergic contact dermatitis is to identify and avoid coming into contact with the chemical that causes the reaction.

Most allergies are attributed to proteins or synthetically produced peptide antigens that set off the immune system.

A new study from the Hamamatsu University School of Medicine has discovered that docosahexaenoic acid (DHA) could potentially be an important component in creating more efficient lip care products.

The university collaborated with Kose Corporations research laboratories in order to better understand the molecular profile of the lip area.

The study highlighted it was especially important to study the lip in closer detail as it was one of the major targets of cosmetics.

Its important to under the molecular profile specific to human lips to discover the intrinsic ingredients for lip cosmetics.

To gain a better understanding, the team aimed to map out the human lip using imaging mass spectrometry to gather insight into its lipid distribution.

Researchers at Kao Corporation have developed a method to predict odour intensity, a skill previously dependent on the experience of perfumers.

The development of the technology was the result of a project by the firms Sensory Science Research Laboratory, which compiled a database of 314 commonly used fragrance ingredients.

The database of olfaction characteristics allowed scientists to develop a method that can predict the odour intensity based on the concentration of perfumery raw materials (PRMs) present in a gas sample.

Data were obtained from an evaluation testing performed by 18 perfumers and researchers, who scored the intensity of samples emitted from a fragrance diluter with different gas concentrations.

Based on evaluations of those results, the team managed to visualise the relationship between gas concentration and odour intensity.

Singapore biotech start-up Insectta is rearing black soldier flies on its urban farm to produce a more sustainable and purer chitosan for the cosmetics industry.

The company, which claims to have the first insect farm in Singapore, raises black soldier flies that feed on food waste before being converted into viable materials such as chitosan.

It is a useful material that has many functions. For cosmetics, it has antioxidant, antimicrobial and wound-healing properties. Additionally, it can enhance penetration into skin.

Chitosan is conventionally sourced from shrimp and crab. However, the company believes using insects is cleaner and more sustainable.

These flies are not pests, they don't bite. They are native to Singapore and not an invasive species. They feed on food waste which would otherwise go into the incinerator. We're trying to promote a circular economy, said Chua Kai Ning, chief marketing officer of Insectta.

The flies on the farm, which are housed in a small room, can consume around 7.5 tonnes of food waste a month.

Experts in Australia have been urging the public to carry on using sunscreen even though a widely publicised study has shown chemicals can be absorbed from some products into the bloodstream.

US Food and Drug Administration scientists found that sunscreen users might be taking in more of the active ingredients into our blood, far beyond regulatory thresholds.

They tested six of the main active ingredients in sunscreen lotions, sprays and pumps, revealing quantities of sunscreen chemicals in the blood high enough for the products to have to undergo additional FDA safety studies.

This happens when formulations surpass a threshold that requires them to be taken for further testing. The chemicals studied were avobenzone, oxybenzone, octocrylene, ecamsule, homosalate, octisalate and octinoxate.

The researchers stress the findings do not mean that sunscreens are unsafe, merely that more research is needed. The FDA will now conduct more research to determine the maximum levels of sunscreen ingredients that are safe to use.

Original post:
Skin science: Top five stories on cosmetics science and formulation - CosmeticsDesign-Asia.com

Recommendation and review posted by Bethany Smith

Article In Brief

A unique molecular structureevident in induced pluripotent stem cells taken from people with young-onset Parkinson's diseasesuggests that the defects may be present throughout patients' lives, and that they could therefore be used as diagnostic markers.

Induced pluripotent stem cells (iPSCs) taken from patients with young-onset Parkinson's disease (YOPD) and grown into dopamine-producing neurons displayed a molecular signature that was corrected in vitro, as well as in the mice striatum, by a drug already approved by the US Food and Drug Administration (FDA), a study published in the January 27 online edition of Nature Medicine found.

Although the patients had no known genetic mutations associated with PD, the neurons grown from their iPSCs nonetheless displayed abnormally high levels of soluble alpha-synucleina classic phenotype of the disease, but one never before seen in iPSCs from patients whose disease developed later in life. Surprisingly, for reasons not yet understood, the cells also had high levels of phosphorylated protein kinase C-alpha (PKC).

In addition, the cells also had another well-known hallmark of PD: abnormally low levels of lysosomal membrane proteins, such as LAMP1. Because lysosomes break down excess proteins like alpha-synuclein, their reduced levels in PD have long been regarded as a key pathogenic mechanism.

When the study team tested agents known to activate lysosomal function, they found that a drug previously approved by the FDA as an ointment for treating precancerous lesions, PEP005, corrected all the observed abnormalities in vitro: it reduced alpha-synuclein and PKC levels while increasing LAMP1 abundance. It also decreased alpha-synuclein production when delivered to the mouse striatum.

Unexpectedly, however, PEP005 did not work by activating lysosomal function; rather, it caused another key protein-clearing cellular structure, the proteasome, to break down alpha-synuclein more readily.

The findings suggest that the defects seen in the iPSCs are present throughout patients' lives, and that they could therefore be used as diagnostic markers. Moreover, the drug PEP005 should be considered a potentially promising therapeutic candidate for YOPD and perhaps even for the 90 percent of PD patients in whom the disease develops after the age of 50, according to the study's senior author, Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and professor of biomedical sciences and medicine at Cedars-Sinai.

These findings suggest that one day we may be able to detect and take early action to prevent this disease in at-risk individuals, said study coauthor Michele Tagliati, MD, FAAN, director of the movement disorders program and professor of neurology at Cedars-Sinai Medical Center.

But the study still raises questions regarding the biological mechanisms, and certainly does not warrant off-label prescribing of PEP005 at this time, said Marco Baptista, PhD, vice president of research programs at the Michael J. Fox Foundation, who was not involved with the study.

Repurposing PEP005 is a long way away, Dr. Baptista said. This is not something that neurologists should be thinking about prescribing or recommending to their patients.

Accumulation of alpha-synuclein has been seen in iPSC-derived dopaminergic cultures taken from patients with known genetic defects, but such defects account for only about 10 percent of the PD population. In those without known mutations, on the other hand, no defects in iPSC-derived dopamine-producing neurons have been seen. Until now, however, such studies had been conducted only in patients who had developed PD after age 50.

My idea was why to look in young-onset patients, said Dr. Svendsen.

The idea paid off more richly than he expected. We were shocked to find a very, very prominent phenotype, a buildup of alpha-synuclein, in the neurons of these patients who are genetically normal, Dr. Svendsen said. None of the controls had a buildup of synuclein, and all but one of the early PD patients had a twofold increase in it.

The signature is so consistent, he said, that it offers a natural model that can be interrogated to further understand its workings.

Because high levels of PKC were also seen, Dr. Svendsen said, We picked a bunch of drugs known to reduce PKC. We found one, PEP005, which is actually extracted from the milkweed plant, and it completely reduced synuclein levels almost to normal in dopaminergic neurons. And it also increased dopamine levels in those cells, so we got two for one.

After observing the effects of PEP005 in vitro, We put it into the mouse brain and found it reduced synuclein in vivo, Dr. Svendsen said. But we had to infuse it right into the brain. We're now trying to work out how to get it across the blood-brain barrier more efficiently.

To determine how PEP005 lowers cellular levels of alpha-synuclein, his group tested whether it was activating the lysosome, but found to their surprise that it did not do this until after the synuclein had already been degraded.

Then we asked whether it could be the proteosome, which also breaks down proteins but normally doesn't break down synuclein, Dr. Svendsen said. But when we applied PEP005, it did activate the proteasome. So we think that might be the mechanism.

Because the drug is currently applied externally, Dr. Svendsen said, the next step will be to see if it crosses the blood-brain barrier when applied to the skin of mice, and whether that results in a lowering of synuclein levels in dopaminergic neurons.

Justin Ichida, PhD, the Richard N. Merkin assistant professor of stem cell biology and regenerative medicine at the USC Keck School of Medicine, said the findings are quite important in the field. The potential diagnostic tools they made could be important in clinical care. And identifying a drug that may very effectively reverse the disease in neurons is a very important discovery.

He wondered, however, whether the increase in alpha-synuclein is truly specific to Parkinson's neurons or if it would also be seen in iPSC neurons from patients with Alzheimer's disease or amyotrophic lateral sclerosis.

I wonder if alpha-synuclein accumulating is a sign of PD in a dish or is a consequence of neurodegeneration or impaired protein degradation in general, Dr. Ichida said. That's a key question if you want to use this molecular signature as a diagnostic tool.

He also questioned if proteins other than alpha-synuclein, such as tau, would also be seen to accumulate in the iPSCs of YOPD patients.

If one of the protein-clearance mechanisms in the cell is working poorly, you would imagine that other things would also accumulate, Dr. Ichida said.

In response, Dr. Svendsen said that while some proteins other than alpha-synuclein were reported in the paper at increased levels, We did not look at tau specifically, but are in the process of looking right now. It could be that synuclein and some other proteins are somehow altered to evade them from being degraded by the lysosome, or that there is a general lysosomal problem.

Patrik Brundin, MD, PhD, director of the Center for Neurodegenerative Science and Jay Van Andel Endowed Chair at Van Andel Research Institute in Grand Rapids, MI, called the paper very interesting and thought-provoking. If these findings hold up, they could shift our understanding of young-onset PD. They imply that there is a strong genetic component that has not been picked up in prior genetic studies.

Dr. Brundin said he would like to see the results replicated in another lab using different sets of reagents. It is so intriguing and rather unexpected that one wonders if the observations really apply, as the study states, to 95 percent of all YOPD.

He also questioned whether all the young-onset PD patients are similar. Clearly the iPSCs studied here are not monogenetic PD, so they must be very diverse genetically and still all have the same alpha-synuclein change.

Dr. Brundin also asked why the abnormalities seen in YOPD neurons have not previously been seen in older cases of PD. Is there a specific cutoff regarding age-of-onset when these purposed genetic differences apply? he asked.

Dr. Svendsen responded: We don't know why the YO have this phenotype or exactly what the cut off is. We have, however, looked at one adult-onset case that did not show this phenotype. Also, one of our YO cases did not show this phenotype. Thus some patients even with early onset may not have it. We are currently testing many more cases from older-onset patients.

Dr. Brundin also wanted to know whether non-dopaminergic neurons have the same deficits described in the study.

We don't know which neurons specifically have the protein deficit as we cannot do single-cell proteomics, Dr. Svendsen answered. It could be a little in all cells or a lot in a small set. Immunocytochemistry is not quantitative but showed that it is more likely a general increase in synuclein and not specific to dopaminergic neurons.

While the findings in iPSCs suggest that the abnormal levels of alpha-synuclein must be present at birth, Dr. Brundin said, I do not know how to reconcile the present findings with genetic data.

The absence of previously described mutations in the YOPD patients means only that more work must be done to uncover the genetic underpinnings, Dr. Svendsen said.

We're just at the tip of the iceberg with understanding the genome, he said. It's such a bizarrely complex beast. Perhaps there are a thousand different proteins interacting to stop the synuclein from being degraded. In 10 years, we probably will be clever enough to see it. We know it must be there. Now the genome guys will go after it.

Dr. Baptista from the Michael J. Fox Foundation said he agreed with the view that there must be genetic alterations underpinning the defects seen in the iPSCs.

Just because we call something non-genetic could simply reflect the current ignorance of the field, he said. I think the discoveries are simply difficult to make.

He added that he wished that the main comparator in the study was not healthy controls, and that there were more older-onset iPSCs to compare against YOPD patients' samples.

Dr. Svendsen said it could be that the iPSCs from older-onset patients might yet be found with additional study to display abnormalities similar to those seen in YOPD.

Right now we only see it in young onset, he said. We may need to leave the cultures longer to see in the older-onset patients. We are doing those experiments now.

Drs. Tagliati and Svendsen disclosed that an intellectual patent is pending for diagnostic and drug screening for molecular signatures of early-onset Parkinson's disease. Dr. Ikeda is a co-founder of AcuraStem Inc. Dr. Brundin has received commercial support as a consultant from Renovo Neural, Inc., Lundbeck A/S, AbbVie, Fujifilm-Cellular Dynamics International, Axial Biotherapeutics, and Living Cell Technologies. He has also received commercial support for research from Lundbeck A/S and Roche and has ownership interests in Acousort AB and Axial Biotherapeutics. Dr. Baptista had no disclosures.

Read the rest here:
Molecular Signature of Young-Onset Parkinson's Disease Is... : Neurology Today - LWW Journals

Recommendation and review posted by Bethany Smith

4-Mar-2020

Ingredients | Skin Care

inspira: cosmetics produces and markets high-quality, contemporary cosmetic products for individual skin care worldwide

The German company is based in Aachen and was founded in 2000. The development of outstanding and highly effective products with excellent compatibility is a matter of course for inspira: cosmetics.

The products visibly improve the appearance of the skin and let the user look in the best possible way for his/her respective age.

Now Volker Kloubert, Managing Partner of inspira: cosmetics proudly announced: "We are more than happy and feel very honoured that 3 of our entries are finalists in the Pure Beauty Global Awards and we are looking forward to the award ceremony in May in Amsterdam. Lets keep fingers crossed!

The finalist products from inspira: cosmetics reflect the broad scope of cosmetics the brand is covering.

The male scent 4MEN ONLY is nominated in the category Best Male Fragrance. A masculine composition of oriental notes, combined with woods and musk. Adventurous and very sexy! For men only. The sophisticated fragrance was created by master perfumers in Grasse/France.

Finalist in the category Best Lip Product is the Volumizing Lip Remedy, a lip care stick in stylish silver metal packaging with high quality active ingredients like hyaluronic acid, shea butter, coconut oil, spearmint oil for a fresh taste and the Peptide Complex VOLULIP than can increase the lip volume by up to 82% in 4 weeks as it stimulates the production of hyaluronic acid in the lips.

Very important: NO burning sensation, the product is smooth as silk.

Age Reboot Serum is the new holistic anti aging serum in the inspira: med range using state of the art active ingredients to protect and rejuvenate the skin.

Phyto stem cells help the skin to adapt to changing environmental conditions like heat or cold and protect the cells whereas three different hyaluronic acids smooth the skin, even out wrinkles and EGF (Epidermal Growth Factor) stimulates cell renewal.

In clinical studies the skin was rejuvenated by up to 10 years in four weeks of regular use.

See the article here:
Three of inspira: cosmetics entries are finalists in the Pure Beauty Global Awards 2020 - Cosmetics Business

Recommendation and review posted by Bethany Smith

Abstract

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery.

Mesenchymal stem cells (MSCs) hold great promise for therapeutic tissue engineering and regenerative medicine, largely because of their capacity for self-renewal and multipotent properties (1). However, their uncertain fate has a major impact on their envisioned therapeutic use. Cell fate regulation requires specific transcription programs in response to environmental cues (2, 3). Once stem cells are removed from their microenvironment, their response to environmental cues, phenotype, and functionality could often be altered (4, 5). In contrast to growing information concerning transcriptional regulation, guidance from the extracellular matrix (ECM) governing MSC identity and fate determination is not well understood. It remains an active area of investigation and may provide previously unidentified avenues for MSC-based therapy.

Over the past decade, engineering three-dimensional (3D) ECM to direct MSC differentiation has demonstrated great potential of MSCs in regenerative medicine (6). 3D ECM has been found to be useful in providing both biochemical and biophysical cues and to stabilize newly formed tissues (7). Culturing cells in 3D ECM radically alters the interfacial interactions with the ECM as compared with 2D ECM, where cells are flattened and may lose their differentiated phenotype (8). However, one limitation of 3D materials as compared to 2D approaches was the lack of spatial control over chemistry with 3D materials. One possible solution to this limitation is 3D bioprinting, which could be used to design the custom scaffolds and tissues (9).

In contrast to traditional engineering techniques, 3D cell printing technology is especially advantageous because it can integrate multiple biophysical and biochemical cues spatially for cellular regulation and ensure complex structures with precise control and high reproducibility. In particular, for our final goal of clinical practice, extrusion-based bioprinting may be more appropriate for translational application. In addition, as a widely used bioink for extrusion bioprinting, alginate-based hydrogel could maintain stemness of MSC due to the bioinert property and improve biological activity and printability by combining gelatin (10).

Sweat glands (SGs) play a vital role in thermal regulation, and absent or malfunctioning SGs in a hot environment can lead to hyperthermia, stroke, and even death in mammals (11, 12). Each SG is a single tube consisting of a functionally distinctive duct and secretory portions. It has low regenerative potential in response to deep dermal injury, which poses a challenge for restitution of lost cells after wound (13). A major obstacle in SG regeneration, similar to the regeneration of most other glandular tissues, is the paucity of viable cells capable of regenerating multiple tissue phenotypes (12). Several reports have described SG regeneration in vitro; however, dynamic morphogenesis was not identified nor was the overall function of the formed tissues explored (1416). Recent advances in bioprinting and tissue engineering led to the complexities in the matrix design and fabrication with appropriate biochemical cues and biophysical guidance for SG regeneration (1719).

Here, we adopted 3D bioprinting technique to mimic the regenerative microenvironment that directed the specific SG differentiation of MSCs and ultimately guided the formation and function of glandular tissue. We used alginate/gelatin hydrogel as bioinks in this present study due to its good cytocompatibility, printability, and structural maintenance in long-time culture. Although the profound effects of ECM on cell differentiation was well recognized, the importance of biochemical and structural cues of 3D-printed matrix that determined the cell fate of MSCs remained unknown; thus, the present study demonstrated the role of 3D-printed matrix cues on cellular behavior and tissue morphogenesis and might help in developing strategies for MSC-based tissue regeneration or directing stem cell lineage specification by 3D bioprinting.

The procedure for printing the 3D MSC-loaded construct incorporating a specific SG ECM (mouse plantar region dermis, PD) was shown schematically in Fig. 1A. A 3D cellular construct with cross section 30 mm 30 mm and height of 3 mm was fabricated by using the optimized process parameter (20). The 3D construct demonstrated a macroporous grid structure with hydrogel fibers evenly distributed according to the computer design. Both the width of the fibers and the gap between the fibers were homogeneous, and MSCs were embedded uniformly in the hydrogel matrix fibers to result in a specific 3D microenvironment. (Fig. 1B).

(A) Schematic description of the approach. (B) Full view of the cellular construct and representative microscopic and fluorescent images and the quantitative parameters of 3D-printed construct (scale bars, 200 m). Photo credit: Bin Yao, Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA. (C) Representative microscopy images of cell aggregates and tissue morphology at 3, 7, and 14 days of culture (scale bars, 50 m) and scanning electron microscopy (sem) images of 3D structure (scale bars, 20 m). PD+/PD, 3D construct with and without PD. (D) DNA contents, collagen, and GAGs of native tissue and PD. (E) Proliferating cells were detected through Ki67 stain at 3, 7, and 14 days of culture. (F) Live/dead assay show cell viability at days 3, 7, and 14. *P < 0.05.

During the maintenance of constructs for stem cell expansion, MSCs proliferated to form aggregates of cells but self-assembled to an SG-like structure only with PD administration (Fig. 1C and fig. S1, A to C). We carried out DNA quantification assay to evaluate the cellular content in PD and found the cellular matrix with up to 90% reduction, only 3.4 0.7 ng of DNA per milligram tissue remaining in the ECM. We also estimated the proportions of collagen and glycosaminoglycans (GAGs) in ECM through hydroxyproline assay and dimethylmethylene blue assay, the collagen contents could increase to 112.6 11.3%, and GAGs were well retained to 81 9.6% (Fig. 1D). Encapsulated cells were viable, with negligible cell death apparent during extrusion and ink gelation by ionic cross-linking, persisting through extended culture in excess of 14 days. The fluorescence intensity of Ki67 of MSCs cultured in 2D condition decreased from days 3 (152.7 13.4) to 14 (29.4 12.9), while maintaining higher intensity of MSCs in 3D construct (such as 211.8 19.4 of PD+3D group and 209.1 22.1 of PD3D group at day 14). And the cell viability in 3D construct was found to be sufficiently high (>80%) when examined on days 3, 7, and 14. The phenomenon of cell aggregate formation and increased cell proliferation implied the excellent cell compatibility of the hydrogel-based construct and promotion of tissue development of 3D architectural guides, which did not depend on the presence or absence of PD (Fig. 1, E and F).

The capability of 3D-printed construct with PD directing MSC to SGs in vitro was investigated. The 3D construct was dissolved, and cells were isolated at days 3, 7, and 14 for transcriptional analysis. Expression of the SG markers K8 and K18 was higher from the 3D construct with (3D/PD+) than without PD (3D/PD); K8 and K18 expression in the 3D/PD construct was similar to with control that MSCs cultured in 2D condition, which implied the key role of PD in SG specification. As compared with the 2D culture condition, 3D administration (PD+) up-regulated SG markers, which indicated that the 3D structure synergistically boosted the MSC differentiation (Fig. 2A).

(A) Transcriptional expression of K8, K18, Fxyd2, Aqp5, and ATP1a1 in 3D-bioprinted cells with and without PD in days 3, 7, and 14 culture by quantitative real-time polymerase chain reaction (qRT-PCR). Data are means SEM. (B) Comparison of SG-specific markers K8 and K18 in 3D-bioprinted cells with and without PD (K8 and K18, red; DAPI, blue; scale bars, 50 m). (C and D) Comparison of SG secretion-related markers ATP1a1 (C) and Ca2+ (D) in 3D-bioprinted cells with and without PD [ATP1a1 and Ca2+, red; 4,6-diamidino-2-phenylindole (DAPI), blue; scale bars, 50 m].

In addition, we tested secretion-related genes to evaluate the function of induced SG cells (iSGCs). Although levels of the ion channel factors of Fxyd2 and ATP1a1 were increased notably in 2D culture with PD and ATP1a1 up-regulated in the 3D/PD construct, all the secretory genes of Fxyd2, ATP1a1, and water transporter Aqp5 showed the highest expression level in the 3D/PD+ construct (Fig. 2A). Considering the remarkable impact, further analysis focused on 3D constructs.

Immunofluorescence staining confirmed the progression of MSC differentiation. At day 7, cells in the 3D/PD+ construct began to express K8 and K18, which was increased at day 14, whereas cells in the 3D/PD construct did not express K8 and K18 all the time (Fig. 2B and fig. S2A). However, the expression of ATP1a1 (ATPase Na+/K+ transporting subunit alpha 1) and free Ca2+ concentration did not differ between cells in the 3D/PD+ and 3D/PD constructs (Fig. 2, C and D). By placing MSCs in such a 3D environment, secretion might be stimulated by rapid cell aggregation without the need for SG lineage differentiation. Cell aggregationimproved secretion might be due to the benefit of cell-cell contact (fig. S2B) (21, 22).

To map the cell fate changes during the differentiation between MSCs and SG cells, we monitored the mRNA levels of epithelial markers such as E-cadherin, occludin, Id2, and Mgat3 and mesenchymal markers N-cadherin, vimentin, Twist1, and Zeb2. The cells transitioned from a mesenchymal status to a typical epithelial-like status accompanied by mesenchymal-epithelial transition (MET), then epithelial-mesenchymal transition (EMT) occurred during the further differentiation of epithelial lineages to SG cells (fig. S3A). In addition, MET-related genes were dynamically regulated during the SG differentiation of MSCs. For example, the mesenchymal markers N-cadherin and vimentin were down-regulated from days 1 to 7, which suggested cells losing their mesenchymal phenotype, then were gradually up-regulated from days 7 to 10 in their response to the SG phenotype and decreased at day 14. The epithelial markers E-cadherin and occludin showed an opposite expression pattern: up-regulated from days 1 to 5, then down-regulated from days 7 to 10 and up-regulated again at day 14. The mesenchymal transcriptional factors ZEB2 and Twist1 and epithelial transcriptional factors Id2 and Mgat3 were also dynamically regulated.

We further analyzed the expression of these genes at the protein level by immunofluorescence staining (figs. S3B and S4). N-cadherin was down-regulated from days 3 to 7 and reestablished at day 14, whereas E-cadherin level was increased from days 3 to 7 and down-regulated at day 14. Together, these results indicated that a sequential and dynamic MET-EMT process underlie the differentiation of MSCs to an SG phenotype, perhaps driving differentiation more efficiently (23). However, the occurrence of the MET-EMT process did not depend on the presence of PD. Thus, a 3D structural factor might also participate in the MSC-specific differentiation (fig. S3C).

To investigate the underlying mechanism of biochemical cues in lineage-specific cell fate, we used quantitative proteomics analysis to screen the ECM factors differentially expressed between PD and dorsal region dermis (DD) because mice had eccrine SGs exclusively present in the pads of their paws, and the trunk skin lacks SGs. In total, quantitative proteomics analyses showed higher expression levels of 291 proteins in PD than DD. Overall, 66 were ECM factors: 23 were significantly up-regulated (>2-fold change in expression). We initially determined the level of proteins with the most significant difference after removing keratins and fibrin: collagen triple helix repeat containing 1 (CTHRC1) and thrombospondin 1 (TSP1) (fig. S5). Western blotting was performed to further confirm the expression level of CTHRC1 and TSP1, and we then confirmed that immunofluorescence staining at different developmental stages in mice revealed increased expression of CTHRC1 in PD with SG development but only slight expression in DD at postnatal day 28, while TSP1 was continuously expressed in DD and PD during development (Fig. 3, A to C). Therefore, TSP1 was required for the lineage-specific function during the differentiation in mice but was not dispensable for SG development.

(A and B) Differential expression of CTHRC1 and TSP1in PD and back dermis (DD) ECM of mice by proteomics analysis (A) and Western blotting (B). (C) CTHRC1 and TSP1 expression in back and plantar skin of mice at different developmental times. (Cthrc1/TSP1, red; DAPI, blue; scale bars, 50 m).

According to previous results of the changes of SG markers, 3D structure and PD were both critical to SG fate. Then, we focused on elucidating the mechanisms that underlie the significant differences observed in 2D and 3D conditions with or without PD treatment. To this end, we performed transcriptomics analysis of MSCs, MSCs treated with PD, MSCs cultured in 3D construct, and MSC cultured in 3D construct with PD after 3-day treatment. We noted that the expression profiles of MSCs treated with 3D, PD, or 3D/PD were distinct from the profiles of MSCs (Fig. 4A). Through Gene Ontology (GO) enrichment analysis of differentially expressed genes, it was shown that PD treatment in 2D condition induced up-regulation of ECM and inflammatory response term, and the top GO term for MSCs in 3D construct was ECM organization and extracellular structure organization. However, for the MSCs with 3D/PD treatment, we found very significant overrepresentation of GO term related to branching morphogenesis of an epithelial tube and morphogenesis of a branching structure, which suggested that 3D structure cues and biochemical cues synergistically initiate the branching of gland lineage (fig S6). Heat maps of differentially expressed ECM organization, cell division, gland morphogenesis, and branch morphogenesis-associated genes were shown in fig. S7. To find the specific genes response to 3D structure cues facilitating MSC reprogramming, we analyzed the differentially expressed genes of four groups of cells (Fig. 4B). The expression of Vwa1, Vsig1, and Hmox1 were only up-regulated with 3D structure stimulation, especially the expression of Hmox1 showed a most significant increase and even showed a higher expression addition with PD, which implied that Hmox1 might be the transcriptional driver of MSC differentiation response to 3D structure cues. Differential expression of several genes was confirmed by quantitative polymerase chain reaction (qPCR): Mmp9, Ptges, and Il10 were up-regulated in all the treated groups. Likewise, genes involving gland morphogenesis and branch morphogenesis such as Bmp2, Tgm2, and Sox9 showed higher expression in 3D/PD-treated group. Bmp2 was up-regulated only in 3D/PD-treated group, combined with the results of GO analysis, we assumed that Bmp2 initiated SG fate through inducing branch morphogenesis and gland differentiation (Fig. 4C).

(A) Gene expression file of four groups of cells (R2DC, MSCs; R2DT, MSC with PD treatment; R3DC, MSC cultured in 3D construct; and R3DT, MSC treated with 3D/PD). (B) Up-regulated genes after treatment (2DC, MSCs; 2DT, MSC with PD treatment; 3DC, MSC cultured in 3D construct; and 3DT, MSC treated with 3D/PD). (C) Differentially expressed genes were further validated by RT-PCR analysis. [For all RT-PCR analyses, gene expression was normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with 40 cycles, data are represented as the means SEM, and n = 3].

To validate the role of HMOX1 and CTHRC1 in the differentiation of MSCs to SG lineages, we analyzed the gene expression of Bmp2 by regulating the expression of Hmox1 and CTHRC1 based on the 3D/PD-treated MSCs. The effects of caffeic acid phenethyl ester (CAPE) and tin protoporphyrin IX dichloride (Snpp) on the expression of Hmox1 were evaluated by quantitative real-time (qRT)PCR. Hmox1 expression was significantly activated by CAPE and reduced by Snpp. Concentration of CTHRC1 was increased with recombinant CTHRC1 and decreased with CTHRC1 antibody. That is, it was negligible of the effects of activator and inhibitor of Hmox1 and CTHRC1 on cell proliferation (fig. S8, A and B). Hmox1 inhibition or CTHRC1 neutralization could significantly reduce the expression of Bmp2, while Hmox1 activation or increased CTHRC1 both activated Bmp2 expression. Furthermore, Bmp2 showed highest expression by up-regulation of Hmox1 and CTHRC1 simultaneously and sharply decreased with down-regulation of Hmox1 and CTHRC1 at the same time (Fig. 5A). Immunofluorescent staining revealed that the expression of bone morphogenetic protein 2 (BMP2) at the translational level with CTHRC1 and Hmox1 regulation showed a similar trend with transcriptional changes (Fig. 5B). Likewise, the expression of K8 and K18 at transcriptional and translational level changed similarly with CTHRC1 and Hmox1 regulation (fig. S9, A and B). These results suggested that CTHRC1 and Hmox1 played an essential role in SG fate separately, and they synergistically induced SG direction from MSCs (Fig. 5C).

(A and B) Transcriptional analysis (A) and translational analysis (PD, MSCs; PD+, MSCs with 3D/PD treatment; CAPE, MSCs treated with 3D/PD and Hmox1 activator; Snpp, MSCs treated with 3D/PD and Hmox1 inhibitor; Cthrc1, MSCs treated with 3D/PD and recombinant CTHRC1; anti, MSCs treated with 3D/PD and CTHRC1 antibody: +/+, MSCs treated with 3D/PD and Hmox1 activator and recombinant CTHRC1; and /, MSCs treated with 3D/PD and Hmox1 inhibitor and CTHRC1 antibody. Data are represented as the means SEM and n = 3) (B) of bmp2 with regulation of CTHRC1 and Hmox1. (C) The graphic illustration of 3D-bioprinted matrix directed MSC differentiation. CTHRC1 is the main biochemical cues during SG development, and structural cues up-regulated the expression of Hmox1 synergistically initiated branching morphogenesis of SG. *P < 0.05.

Next, we sought to assess the repair capacity of iSGCs for in vivo implications, the 3D-printed construct with green fluorescent protein (GFP)labeled MSCs was transplanted in burned paws of mice (Fig. 6A). We measured the SG repair effects by iodine/starch-based sweat test at day 14. Only mice with 3D/PD treatment showed black dots on foot pads (representing sweating), and the number increased within 10 min; however, no black dots were observed on untreated and single MSC-transplanted mouse foot pads even after 15 min (Fig. 6B). Likewise, hematoxylin and eosin staining analysis revealed SG regeneration in 3D/PD-treated mice (Fig. 6C). GFP-positive cells were characterized as secretory lumen expressing K8, K18, and K19. Of note, the GFP-positive cells were highly distributed in K14-positive myoepithelial cells of SGs but were absent in K14-positive repaired epidermal wounds (Fig. 6, D and E). Thus, differentiated MSCs enabled directed restitution of damaged SG tissues both at the morphological and functional level.

(A) Schematic illustration of approaches for engineering iSGCs and transplantation. (B) Sweat test of mice treated with different cells. Photo credit: Bin Yao, Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA. (C) Histology of plantar region without treatment and transplantation of MSCs and iSGCs (scale bars, 200 m). (D) Involvement of GFP-labeled iSGCs in directed regeneration of SG tissue in thermal-injured mouse model (K14, red; GFP, green; DAPI, blue; scale bar, 200 m). (E) SG-specific markers K14, K19, K8, and K18 detected in regenerated SG tissue (arrows). (K14, K19, K8, and K18, red; GFP, green; scale bars, 50 m).

A potential gap in MSC-based therapy still exists between current understandings of MSC performance in vivo in their microenvironment and their intractability outside of that microenvironment (24). To regulate MSCs differentiation into the right phenotype, an appropriate microenvironment should be created in a precisely controlled spatial and temporal manner (25). Recent advances in innovative technologies such as bioprinting have enabled the complexities in the matrix design and fabrication of regenerative microenvironments (26). Our findings demonstrated that directed differentiation of MSCs into SGs in a 3D-printed matrix both in vitro and in vivo was feasible. In contrast to conventional tissue-engineering strategies of SG regeneration, the present 3D-printing approach for SG regeneration with overall morphology and function offered a rapid and accurate approach that may represent a ready-to-use therapeutic tool.

Furthermore, bioprinting MSCs successfully repaired the damaged SG in vivo, suggesting that it can improve the regenerative potential of exogenous differentiated MSCs, thereby leading to translational applications. Notably, the GFP-labeled MSC-derived glandular cells were highly distributed in K14-positive myoepithelial cells of newly formed SGs but were absent in K14-positive repaired epidermal wounds. Compared with no black dots were observed on single MSC-transplanted mouse foot pads, the black dots (representing sweating function) can be observed throughout the entire examination period, and the number increased within 10 min on MSC-bioprinted mouse foot pads. Thus, differentiated MSCs by 3D bioprinting enabled exclusive restitution of damaged SG tissues morphologically and functionally.

Although several studies indicated that engineering 3D microenvironments enabled better control of stem cell fates and effective regeneration of functional tissues (2730), there were no studies concerning the establishment of 3D-bioprinted microenvironments that can preferentially induce MSCs differentiating into glandular cells with multiple tissue phenotypes and overall functional tissue. To find an optimal microenvironment for promoting MSC differentiation into specialized progeny, biochemical properties are considered as the first parameter to ensure SG specification. In this study, we used mouse PD as the main composition of a tissue-specific ECM. As expected, this 3D-printed PD+ microenvironment drove the MSC fate decision to enhance the SG phenotypic profile of the differentiated cells. By ECM differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator of 3D-printed matrix for SG specification. TSP1 was required for the lineage-specific function during the differentiation in mice but was not dispensable for SG development. Thus, we identified CTHRC1 as a specific factor during SG development. To our knowledge, this is the first demonstration of CTHRC1 involvement in dictating MSC differentiation to SG, highlighting a potential therapeutic tool for SG injury.

The 3D-printed matrix also provided architectural guides for further SG morphogenesis. Our results clearly show that the 3D spatial dimensionality allows for better cell proliferation and aggregation and affect the characteristics of phenotypic marker expression. Notably, the importance of 3D structural cues on MSC differentiation was further proved by MET-EMT process during differentiation, where the influences did not depend on the presence of biochemical cues. To fully elucidate the underlying mechanisms, we first examined how 3D structure regulating stem cell fate choices. According to our data, Hmox1 is highly up-regulated in 3D construct, which were supposed to response to hypoxia, with a previously documented role in MSC differentiation (31, 32). It is suggested that 3D microenvironment induced rapid cell aggregation leading to hypoxia and then activated the expression of Hmox1.

Through regulation of the expression of Hmox1 and addition or of CTHRC1 in the matrix, we confirmed that each of them is critical for SG reprogramming, respectively. Thus, biochemical and structural cues of 3D-printed matrix synergistically creating a microenvironment could enhance the accuracy and efficiency of MSC differentiation, thereby leading to resulting SG formation. Although we further need a more extensive study examining the role of other multiple cues and their possible overlap function in regulating MSC differentiation, our findings suggest that CTHRC1 and Hmox1 provide important signals that cooperatively modulate MSC lineage specification toward sweat glandular lineage. The 3D structure combined with PD stimulated the GO functional item of branch morphogenesis and gland formation, which might be induce by up-regulation of Bmp2 based on the verification of qPCR results. Although our results could not rule out the involvement of other factors and their possible overlapping role in regulating MSC lineage specification toward SGs, our findings together with several literatures suggested that BMP2 plays a critical role in inducing branch morphogenesis and gland formation (3335).

In summary, our findings represented a novel strategy of directing MSC differentiation for functional SG regeneration by using 3D bioprinting and pave the way for a potential therapeutic tool for other complex glandular tissues as well as further investigation into directed differentiation in 3D conditions. Specifically, we showed that biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation, and our results highlighted the importance of 3D-printed matrix cues as regulators of MSC fate decisions. This avenue opens up the intriguing possibility of shifting from genetic to microenvironmental manipulations of cell fate, which would be of particular interest for clinical applications of MSC-based therapies.

The main aim and design of the study was first to determine whether by using 3D-printed microenvironments, MSCs can be directed to differentiate and regenerate SGs both morphologically and functionally. Then, to investigate the underlying molecular mechanism of biochemical and structural cues of 3D-printed matrix involved in MSCs reprogramming. The primary aims of the study design were as follows: (i) cell aggregation and proliferation in a 3D-bioprinted construct; (ii) differentiation of MSCs at the cellular phenotype and functional levels in the 3D-bioprinted construct; (iii) the MET-EMT process during differentiation; (iv) differential protein expression of the SG niche in mice; (v) differential genes expression of MSCs in 3D-bioprinted construct; (vi) the key role of CTHRC1 and HMOX1 in MSCs reprogramming to SGCs; and (vii) functional properties of regenerated SG in vivo.

Gelatin (Sigma-Aldrich, USA) and sodium alginate (Sigma-Aldrich, USA) were dissolved in phosphate-buffered saline (PBS) at 15 and 1% (w/v), respectively. Both solutions were sterilized under 70C for 30 min three times at an interval of 30 min. The sterilized solutions were packed into 50-ml centrifuge tubes, stored at 4C, and incubated at 37C before use.

From wild-type C57/B16 mice (Huafukang Co., Beijing) aged 5 days old, dermal homogenates were prepared by homogenizing freshly collected hairless mouse PD with isotonic phosphate buffer (pH 7.4) for 20 min in an ice bath to obtain 25% (w/v) tissue suspension. The supernatant was obtained after centrifugation at 4C for 20 min at 10,000g. The DNA content was determined using Hoechst 33258 assay (Beyotime, Beijing). The fluorescence intensity was measured to assess the amount of remaining DNA within the decellularized ECMs and the native tissue using a fluorescence spectrophotometer (Thermo Scientific, Evolution 260 Bio, USA). The GAGs content was estimated via 1,9-dimethylmethylene blue solution staining. The absorbance was measured with microplate reader at wavelength of 492 nm. The standard curve was made using chondroitin sulfate A. The total COL (Collagen) content was determined via hydroxyproline assay. The absorbance of the samples was measured at 550 nm and quantified by referring to a standard curve made with hydroxyproline.

MSCs were bioprinted with matrix materials by using an extrusion-based 3D bioprinter (Regenovo Co., Bio-Architect PRO, Hangzhou). Briefly, 10 ml of gelatin solution (10% w/v) and 5 ml of alginate solution (2% w/v) were warmed under 37C for 20 min, gently mixed as bioink and used within 30 min. MSCs were collected from 100-mm dishes, dispersed into single cells, and 200 l of cell suspension was gently mixed with matrix material under room temperature with cell density 1 million ml1. PD (58 g/ml) was then gently mixed with bioink. Petri dishes at 60 mm were used as collecting plates in the 3D bioprinting process. Within a temperature-controlled chamber of the bioprinter, with temperature set within the gelation region of gelatin, the mixture of MSCs and matrix materials was bioprinted into a cylindrical construct layer by layer. The nozzle-insulation temperature and printing chamber temperature were set at 18 and 10C, respectively; nozzles with an inner diameter of 260 m were chosen for printing. The diameter of the cylindrical construct was 30 mm, with six layers in height. After the temperature-controlled bioprinting process, the printed 3D constructs were immersed in 100-mM calcium chloride (Sigma-Aldrich, USA) for 3 min for cross-linking, then washed with Dulbeccos modified Eagle medium (DMEM) (Gibco, USA) medium for three times. The whole printing process was finished in 10 min. The 3D cross-linked construct was cultured in DMEM in an atmosphere of 5% CO2 at 37C. The culture medium was changed to SG medium [contains 50% DMEM (Gibco, New York, NY) and 50% F12 (Gibco) supplemented with 5% fetal calf serum (Gibco), 1 ml/100 ml penicillin-streptomycin solution, 2 ng/ml liothyronine sodium (Gibco), 0.4 g/ml hydrocortisone succinate (Gibco), 10 ng/ml epidermal growth factor (PeproTech, Rocky Hill, NJ), and 1 ml/100 ml insulin-transferrin-selenium (Gibco)] 2 days later. The cell morphology was examined and recorded under an optical microscope (Olympus, CX40, Japan).

Fluorescent live/dead staining was used to determine cell viability in the 3D cell-loaded constructs according to the manufacturers instructions (Sigma-Aldrich, USA). Briefly, samples were gently washed in PBS three times. An amount of 1 M calcein acetoxymethyl (calcein AM) ester (Sigma-Aldrich, USA) and 2 M propidium iodide (Sigma-Aldrich, USA) was used to stain live cells (green) and dead cells (red) for 15 min while avoiding light. A laser scanning confocal microscopy system (Leica, TCSSP8, Germany) was used for image acquisition.

The cell-printed structure was harvested and fixed with a solution of 4% paraformaldehyde. The structure was embedded in optimal cutting temperature (OCT) compound (Sigma-Aldrich, USA) and sectioned 10-mm thick by using a cryotome (Leica, CM1950, Germany). The sliced samples were washed repeatedly with PBS solution to remove OCT compound and then permeabilized with a solution of 0.1% Triton X-100 (Sigma-Aldrich, USA) in PBS for 5 min. To reduce nonspecific background, sections were treated with 0.2% bovine serum albumin (Sigma-Aldrich, USA) solution in PBS for 20 min. To visualize iSGCs, sections were incubated with primary antibody overnight at 4C for anti-K8 (1:300), anti-K14 (1:300), anti-K18 (1:300), anti-K19 (1:300), anti-ATP1a1 (1:300), anti-Ki67 (1:300), antiN-cadherin (1:300), antiE-cadherin (1:300), anti-CTHRC1 (1:300), or anti-TSP1 (1:300; all Abcam, UK) and then incubated with secondary antibody for 2 hours at room temperature: Alexa Fluor 594 goat anti-rabbit (1:300), fluorescein isothiocyanate (FITC) goat anti-rabbit (1:300), FITC goat anti-mouse (1:300), or Alexa Fluor 594 goat anti-mouse (1:300; all Invitrogen, CA). Sections were also stained with 4,6-diamidino-2-phenylindole (Beyotime, Beijing) for 15 min. Stained samples were visualized, and images were captured under a confocal microscope.

To harvest the cells in the construct, the 3D constructs were dissolved by adding 55 mM sodium citrate and 20 mM EDTA (Sigma-Aldrich, USA) in 150 mM sodium chloride (Sigma-Aldrich, USA) for 5 min while gently shaking the petri dish for better dissolving. After transfer to 15-ml centrifuge tubes, the cell suspensions were centrifuged at 200 rpm for 3 min, and the supernatant liquid was removed to harvest cells for further analysis.

Total RNA was isolated from cells by using TRIzol reagent (Invitrogen, USA) following the manufacturers protocol. RNA concentration was measured by using a NanoPhotometer (Implen GmbH, P-330-31, Germany). Reverse transcription involved use of a complementary DNA synthesis kit (Takara, China). Gene expression was analyzed quantitatively by using SYBR green with the 7500 Real-Time PCR System (Takara, China). The primers and probes for genes were designed on the basis of published gene sequences (table S1) (National Center for Biotechnology Information and PubMed). The expression of each gene was normalized to that for glyceraldehyde-3-phosphate dehydrogenase and analyzed by the 2-CT method. Each sample was assessed in triplicate.

The culture medium was changed to SG medium with 2 mM CaCl2 for at least 24 hours, and cells were loaded with fluo-3/AM (Invitrogen, CA) at a final concentration of 5 M for 30 min at room temperature. After three washes with calcium-free PBS, 10 M acetylcholine (Sigma-Aldrich, USA) was added to cells. The change in the Fluo 3 fluorescent signal was recorded under a laser scanning confocal microscopy.

Cell proliferation was evaluated through CCK-8 (Cell counting kit-8) assay. Briefly, cells were seeded in 96-well plates at the appropriate concentration and cultured at 37C in an incubator for 4 hours. When cells were adhered, 10 l of CCK-8 working buffer was added into the 96-well plates and incubated at 37C for 1 hour. Absorbance at 450 nm was measured with a microplate reader (Tecan, SPARK 10M, Austria).

Proteomics of mouse PD and DD involved use of isobaric tags for relative and absolute quantification (iTRAQ) in BGI Company, with differentially expressed proteins detected in PD versus DD. Twofold greater difference in expression was considered significant for further study.

Tissues were grinded and lysed in radioimmunoprecipitation assay buffer (Beyotime, Nanjing). Proteins were separated by 12% SDSpolyacrylamide gel electrophoresis and transferred to a methanol-activated polyvinylidene difluoride membrane (GE Healthcare, USA). The membrane was blocked for 1 hour in PBS with Tween 20 containing 5% bovine serum albumin (Sigma-Aldrich, USA) and probed with the antibodies anti-CTHRC1 (1:1000) and anti-TSP1 (1:1000; both Abcam, UK) overnight at 4C. After 2 hours of incubation with goat anti-rabbit horseradish peroxidaseconjugated secondary antibody (Santa Cruz Biotechnology, CA), the protein bands were detected by using luminal reagent (GE Healthcare, ImageQuant LAS 4000, USA).

Total RNA was prepared with TRIzol (Invitrogen), and RNA sequencing was performed using HiSeq 2500 (Illumina). Genes with false discovery rate < 0.05, fold difference > 2.0, and mean log intensity > 2.0 were considered to be significant.

CAPE or Snpp was gently mixed with bioink at a concentration of 10 M. Physiological concentration of CTHRC1 was measured by enzyme linked immunosorbent assay (ELISA) (80 ng/ml), and then recombinant CTHRC1 or CTHRC1 antibody was added into the bioink at a concentration of 0.4 g/ml. The effect of inhibitor and activator was estimated by qRT-PCR or ELISA.

Mice were anesthetized with pentobarbital (100 mg/kg) and received subcutaneous buprenorphine (0.1 mg/kg) preoperatively. Full-thickness scald injuries were created on paw pads with soldering station (Weller, WSD81, Germany). Mice recovered in clean cages with paper bedding to prevent irritation or infection. Mice were monitored daily and euthanized at 30 days after wounding. Mice were maintained in an Association for Assessment and Accreditation of Laboratory Animal Careaccredited animal facility, and procedures were performed with Institutional Animal Care and Use Committeeapproved protocols.

MSCs in 3D-printed constructs with PD were cultured with DMEM for 2 days and then replaced with SG medium. The SG medium was changed every 2 days, and cells were harvested on day 12. The K18+ iSGCs were sorting through flow cytometry and injected into the paw pads (1 106 cells/50 l) of the mouse burn model by using Microliter syringes (Hamilton, 7655-01, USA). Then, mice were euthanized after 14 days; feet were excised and fixed with 10% formalin (Sigma-Aldrich, USA) overnight for paraffin sections and immunohistological analysis.

The foot pads of anesthetized treated mice were first painted with 2% (w/v) iodine/ethanol solution then with starch/castor oil solution (1 g/ml) (Sigma-Aldrich, USA). After drying, 50 l of 100 M acetylcholine (Sigma-Aldrich, USA) was injected subcutaneously into paws of mice. Pictures of the mouse foot pads were taken after 5, 10, and 15 min.

All data were presented as means SEM. Statistical analyses were performed using GraphPad Prism7 statistical software (GraphPad, USA). Significant differences were calculated by analysis of variance (ANOVA), followed by the Bonferroni test when performing multiple comparisons between groups. P < 0.05 was considered as a statistically significant difference.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/10/eaaz1094/DC1

Fig. S1. Biocompatibility of 3D-bioprinted construct and cellular morphology in 2D monolayer culture.

Fig. S2. Expression of SG-specific and secretion-related markers in MSCs and SG cells in vitro.

Fig. S3. Transcriptional and translational expression of epithelial and mesenchymal markers in 3D-bioprinted cells with and without PD.

Fig. S4. Expression of N- and E-cadherin in MSCs and SG cells in 2D monolayer culture.

Fig. S5. Proteomic microarray assay of differential gene expression between PD and DD ECM in postnatal mice.

Fig. S6. GO term analysis of differentially expressed pathways.

Fig. S7. Heat maps illustrating differential expression of genes implicated in ECM organization, cell division, and gland and branch morphogenesis.

Fig. S8. The expression of Hmox1 and the concentration of CTHRC1 on treatment and the related effects on cell proliferation.

Fig. S9. The expression of K8 and K18 with Hmox1 and CTHRC1 regulation.

Table S1. Primers for qRT-PCR of all the genes.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: Funding: This study was supported in part by the National Nature Science Foundation of China (81571909, 81701906, 81830064, and 81721092), the National Key Research Development Plan (2017YFC1103300), Military Logistics Research Key Project (AWS17J005), and Fostering Funds of Chinese PLA General Hospital for National Distinguished Young Scholar Science Fund (2017-JQPY-002). Author contributions: B.Y. and S.H. were responsible for the design and primary technical process, conducted the experiments, collected and analyzed data, and wrote the manuscript. Y.W. and R.W. helped perform the main experiments. Y.Z. and T.H. participated in the 3D printing. W.S. and Z.L. participated in cell experiments and postexamination. S.H. and X.F. collectively oversaw the collection of data and data interpretation and revised the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Not all signs of blood cancer are easily identifiable, or are associated with typical symptoms of cancer, such as a lump or abnormal mole, says haematologist Dr Manos Nikolousis, a medical consultant with UK blood cancer charity DKMS.

Blood cancer often presents in ways which are most commonly associated with unrelated and less serious illnesses, like a cold or flu. In other circumstances, patients notice a change in their body which they cant quite put their finger on.

One of the treatments for blood cancer is a stem cell transplant that restores blood-forming stem cells in patients whove had theirs destroyed by very high doses of chemotherapy and/or radiotherapy. But Nikolousis points out that only one in three blood cancer patients who need a transplant find a matching blood stem cell donor in their family. The remaining two-thirds have to rely on an unrelated donor, which significantly reduces their chance of finding a crucial match.

Here, Nikolousis outlines some blood cancer symptoms and warning signs...

Musculoskeletal pain in muscles, joints, tendons, bones or structures that support the limbs, neck or back.

One of the most common symptoms associated with blood cancer. The frequency and lasting impact of bruising can be a key warning sign, so its important to book an appointment with your GP if this develops.

Unexplained and persistent tiredness is one of the biggest tell-tale signs of blood cancer. People who have cancer-related fatigue find it incredibly challenging to complete simple tasks that we tend to take for granted.

The lymph nodes are small lumps of tissue that contain white blood cells. When inflamed, they can be felt as lumps under the skin; most commonly in the neck, armpit or groin area.

There may be new headaches that feel different. Theyre likely to occur frequently and be severe and long-lasting.

Persistent abdominal discomfort, presenting as a sharp pain or a sense of feeling full.

This can be described as a feeling of pins and needles/numbness that moves up to the legs, or from fingers to the arms.

This can feel like a fluttering, a sudden thump or a fast pounding sensation in the chest. It can also be felt in the neck or ear when lying down.

People may describe this as feeling mentally drained or dizzy.

Blood cancer patients may have continuous trouble falling asleep or staying asleep.

Persistent and irritable, this may be experienced all over the body, or in isolated spots.

These symptoms are common and dont automatically mean you have cancer. But if you notice any unusual or ongoing changes, its always best to see your doctor and get checked.

See the original post:
Eleven symptoms of blood cancer that everybody needs to know about... - Echo Live

Recommendation and review posted by Bethany Smith

Buyers looking to own a private, well-stocked fishing pond or enjoy the simplicity of a quiet paddle across 18 acres of tranquil water will find all of that and a 5,619-square-foot custom contemporary home at 355 Pond St. in Uxbridge.

Set back from the road on more than 56 scenic acres, the 10-room home, on the market for $1.1 million, offers unique upgrades such as cedar paneled ceilings and 14-karate-gold plated fixtures in the master bath.

The house also features a 2,400-square-foot, wraparound deck that overlooks Lee Pond.

Owner Dr. Charles A. Vacanti said his favorite feature of the property is its pond, which is stocked upstream along Emerson Brook by two fishing clubs.

Both of their ponds drain into our 18-acre pond, he said. It may be the best fishing hole in New England.

Listing agent Gary Smith of Mendon Area Real Estate called the pond and its surrounding property beautiful, while his favorite feature in the home is the spectacular family room.

The sunken combination family and dining room share a wood burning stove with a two-story stone surround. The cathedral ceilings are paneled in cedar and hold skylights and fans. Light from two panels of floor to ceiling glass brightens this room that gives access to the deck.

The modern, eat-in kitchen holds a center island, custom-built cabinetry, granite countertops and large pantry.

The upstairs hallway is an open loft overlooking the family/dining room.

The master suite offers scenic views through a wall of glass with a door that opens to a balcony. The master bath has marble flooring, a cathedral ceiling with skylights, custom built closet and cabinets, a spa hot tub, and large stall shower.

Also upstairs are an office and gym space.

Dr. Vacanti and his wife, Linda, bought the property in 1998.

Since then, the couple has replaced all 27 skylights, all external doors and windows, and the roof. The installation of solar panels, Dr. Vacanti said, has reduced annual utility costs to nearly zero.

Dr. Vacanti is widely known for his research work in stem cell and tissue engineering. While at the University of Massachusetts Medical School in 1996, he grew new cartilage in the shape of a human ear under the skin of a lab mouse. The Vacanti Mouse was part of research on organ generation and the first demonstration of growing new tissue from cells in a lab.

As for the property, Smith called it a beautiful high and dry pasture that just begs for equestrian use, a corporate retreat, Bed and Breakfast, or Rod and Gun Club.

The property is minutes from Route 146.

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House of the Week: Uxbridge property is a sportsmans paradise - Worcester Telegram

Recommendation and review posted by Bethany Smith

New Delhi: The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions.

Stem cell treatments for brain or neural diseases like Parkinsons and Alzheimers disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

Undifferentiated cells that are able to differentiate and transform into any type of cells of the body when and where needed. They have an enormous potential to repair, heal and regenerate. Stem cells come from blood, bone marrow, umbilical cord blood and adipose tissue.

Autologous stem cell therapy: Patient receives stem cells from his/her own body

Allogeneic stem cell therapy: Patient receives the stem cells donated by another individual

Autologous stem cell therapy is better than allogeneic stem cell therapy as chances of mismatching are not there and they pose the minimum risk of immune rejection. Also, no side effects or adverse effects are seen as a persons own blood cells are used. They start the healing process immediately in a natural way.

The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. Stem cells can be obtained from the bone marrow, adipose tissues etc. Due to their tremendous potential to prevent and to treat various health conditions and to repair the injured tissues global research investigation is continuously being done as to explore the maximum advantage of these cell lines.

The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinsons and Alzheimers disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

Depending upon the disease, different stem cell source can be used in a specific condition. The procedure may involve the extraction of stem cells from adipose tissue-derived stem cells with the combination of PRP (Platelet-rich plasma) or can be obtained from bone marrow that can differentiate into progenitor cells that differentiate into various other tissues which can help in the therapy.

The stem cells are isolated from the bone marrow or adipose tissues followed by their processing and enrichment under sterile conditions. These activated stem cells are placed back into the patients body at the target site for repairing the damaged tissue. It is necessary that the stem cells are injected in the specific area of injury as only then the desired results will be achieved.

Adipose stem cells are preferred over bone marrow stem cells as they are easy to isolate and contain a higher number of stem cells.

The stem cells injections are gaining much interest because it is devoid of the painful procedure, takes less time in comparison to surgery, there are no host and recipient rejections as stem cells are harvested from the patients body itself and a targeted delivery system is available.

The stem cells obtained are processed in a sophisticated stem cell lab and after activation is inserted back into the host with the help of intravenous, intramuscular, intraarterial, intradermal and intrathecal injections as per the requirement of the treatment process.

What is the use of anaesthetics and why? Usually, local anaesthetics are used during a stem cell procedure to numb the area but sometimes general anaesthesia is also given while extracting the stem cells from bone marrow. But it is necessary to find out what anaesthetic your doctor uses during orthopaedic stem cell treatments.

A number of anaesthetics have been found to kill the stem cells thus; the treatments end result will greatly depend on the use of anaesthetics. Some anaesthetics very well sync with the stem cell and hence, aid in the treatment.

Stem cells are to be extracted and processed in a clean room, under aseptic conditions maintaining a controlled environment. The doctor should explain the entire process and the number of viable stem cells infused into the patient during the process. Also, the precision of the injections to provide good quality of stem cells at the site of injury will help in better and faster recovery of the patients damaged area.

Cost of the treatment and its duration varies from one patient to another. The disease which needs to be cured, the severity, age factor, health condition, etc, define the duration of the therapy. One may respond during the treatment phase itself while the other may show results after a few sessions or weeks. Depending upon the disease diagnosed, the stem cells extracted, duration of the therapy, other adjuvants used in the process, the cost of the stem cell therapy can vary.

It is essential that after the stem cell therapy the patient should visit the stem cell doctor for recuperation therapies. The primary goals of such therapy is the prevention of secondary complications, analysis of the recovery of motor, sensory and all the bodily functioning, psychological support/counselling for depression, mood swings or anxiety etc. and reintegration into the community.

There can be different sets of precautions which need to be followed at various steps for the recovery of the damaged tissues. The treatment and post-treatment conditions may vary from person to person depending upon the disease and the severity.

Stem cell therapy has shown results in treating serious ailments like leukaemia, grafting tissues, autism, orthopaedic conditions and skin problems etc. Stem Cell Therapy has been successfully used in the treatment of around 80 serious disorders.

Survival rates among patients who received stem cell treatment are significantly high, whether cell donors are related or unrelated to them. With the ongoing research around the world, scientists are exploring new possibilities in which a number of life-threatening diseases can be prevented and cured hence, the stem cells have proved to be promising in the near future as many aspects are yet to be revealed.

Read: Egg stem cells do not exist, says researchers

-IANS

More here:
10 things to know about stem cell therapy - Newsd.in

Recommendation and review posted by Bethany Smith

Technology Networksrecently had the pleasureof speaking with Bruce Steel, CEOEquillium, Inc. to learn more about how they are leveraging their comprehensive understanding of immunobiology to develop novel treatments for inflammatory and autoimmune disorders.Bruce provides insight on the various indications the company is currently developing treatments for, elaborates on the clinical progress of their initial product candidate EQ001 (itolizumab), and explains the role CD6 plays in autoimmunity and how it can be targeted therapeutically.

Laura Lansdowne (LL): How can immunobiology be harnessed to develop therapeutics?Bruce Steel (BS): The role of the immune system is to defend the body against foreign organisms and cells, including cancerous cells, and in doing so, it must distinguish accurately between self- and non-self-entities a process called tolerance. Autoimmunity is an immune response directed against the bodys own healthy cells and tissues and is the underlying process in many inflammatory diseases. Autoimmunity results from a loss of tolerance caused in part by an imbalance in the relationship between effector T cells and regulatory T cells. Therefore, developing therapeutics, such as EQ001 (itolizumab), that target these critical regulators of immune activation pathways has the potential dramatically improve the lives of patients with severe autoimmune and inflammatory disorders.LL: What indications are you currently developing treatments for?BS: We select target indications based on three primary criteria: strong scientific rationale for why itolizumab has potential to be a best-in-class therapeutic approach, areas of high unmet medical need where there are little or no treatments available today, and indications where we believe there is an attractive future commercial opportunity. Today we have ongoing clinical trials with itolizumab in acute graft-versus-host disease (GVHD), uncontrolled asthma and lupus/lupus nephritis.

While these three indications are our initial areas of focus, we believe itolizumab has the potential to be developed in other areas such as transplant science, systemic autoimmunity, pulmonary, neurologic, gastrointestinal, renal, vascular, ophthalmic and dermatologic disorders.We licensed itolizumab from our partner Biocon Limited who developed the drug and received regulatory approval in India for the treatment of psoriasis.LL: Can you tell us more about the mechanism of your drug candidate EQ001 (itolizumab)?BS: Itolizumab is a clinical-stage, first-in-class monoclonal antibody that selectively targets the CD6-ALCAM pathway, which plays a central role in modulating the activity and trafficking of effector T cells that drive a number of immune-inflammatory diseases.LL: What role does CD6 play in autoimmunity?BS: CD6 is a novel co-stimulatory receptor that uniquely modulates T cell activity and trafficking. It is a key checkpoint in regulating effector T cells that are central to autoimmune responses. CD6 binds activated leukocyte cell adhesion molecule (ALCAM). ALCAM is expressed on both antigen-presenting cells and tissue including the skin, gut, lung and kidney.In preclinical studies, blockade of CD6 with itolizumab leads to reduction in effector T cell activation and proliferation. Additionally, inhibiting the binding of ALCAM to CD6 with itolizumab modulates lymphocyte trafficking and reduces effector T cell infiltration into inflamed tissues.

Our work with CD6 builds upon the research conducted from researchers at the Dana-Farber Cancer Institute, our partner Biocon, and other leading academic centers. Today there are numerous peer reviewed publications related to the novel CD6 checkpoint receptor and targeting the CD6-ALCAM pathway.LL: Can you elaborate on the clinical progress of itolizumab?BS: Itolizumab is currently being studied in three different indications: acute graft-versus-host disease (aGVHD), uncontrolled moderate to severe asthma and lupus/lupus nephritis. This is an important catalyst year for Equillium as we expect initial data from all three programs in 2H 2020.

Each of these studies will allow us to understand the safety of itolizumab in these different disease areas and understand what potential dose we will carry forward. This is important as we consider making a larger investment in Phase II studies to advance the program.Bruce Steel was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.

Excerpt from:
Exploiting Immunobiology To Treat Severe Autoimmune and Inflammatory Disorders - Technology Networks

Recommendation and review posted by Bethany Smith

Avoid close contact with sick patients. Stay home if youre feeling unwell. Scrub your hands with soap and water for at least 20 seconds and for goodness sake, stop touching your face.

By now, youve probably heard or seen the advice from the Centers for Disease Control and Prevention (CDC) for staving off COVID-19, the viral epidemic ricocheting across the globe. Most cases of the disease are mild, triggering cold-like symptoms including fever, fatigue, dry cough and shortness of breath. The death rate appears to be lowabout two or three percent, perhaps much less. But the virus responsible, called SARS-CoV-2, is a fearsomely fast spreader, hopping from person to person through the droplets produced by sneezes and coughs. Since COVID-19 was first detected in Chinas Hubei province in December 2019, nearly 100,000 confirmed cases have been reported worldwide, with many more to come.

To curb the virus spread, experts stress the importance of hand hygiene: keeping your hands clean by regularly lathering up with soap and water, or, as a solid second choice, thoroughly rubbing them down with an alcohol-based sanitizer. That might sound like simple, even inconsequential advice. But such commonplace practices can be surprisingly powerful weapons in the war against infectious disease.

[Washing your hands] is one of the most important ways to interrupt transmission of viruses or other pathogens, says Sallie Permar, a physician and infectious disease researcher at Duke University. It can have a major impact on an outbreak.

In the strictest sense of the word, viruses arent technically alive. Unlike most other microbes, which can grow and reproduce on their own, viruses must invade a host such as a human cell to manufacture more of themselves. Without a living organism to hijack, viruses cant cause illness. Yet viral particles are hardy enough to remain active for a while outside of the host, with some staying infectious for hours, days or weeks. For this reason, viruses can easily spread unnoticed, especially when infected individuals dont always exhibit symptomsas appears to be the case with COVID-19.

Researchers are still nailing down the details of exactly how SARS-CoV-2 is transmitted and how resilient it is outside the body. Because the virus seems to hang out in mucus and other airway fluids, it almost certainly spreads when infected individuals cough or sneeze. Released into the air, infectious droplets can land on another person or a frequently touched surface like a doorknob, shopping cart or subway seat. The virus can also transfer through handshakes after someone carrying the virus sneezes or coughs into their hand.

After that, its a short trip for the virus from hand to head. Researchers estimate that, on average, humans touch their faces upwards of 20 times an hour, with about 44 percent of these encounters involving eyes, mouths and nosessome of the quickest entry points into the bodys interior.

Breaking this chain of transmission can help stem the spread of disease, says Chidiebere Akusobi, an infectious disease researcher at Harvards School of Public Health. Sneezing or coughing into your elbow can keep mucus off your mitts; noticing when your hand drifts towards your face can help you reduce the habit.

All this public-health-minded advice boils down to a game of keep away. To actually infect a person, viruses must first get inside the body, where they can infect living cellsso if one lands on your hands, the best next move is to remove or destroy it.

The most important step to curbing infection may be hand-washing, especially before eating food, after using the bathroom and after caring for someone with symptoms. Its simply the best method to limit transmission, says Kellie Jurado, a virologist at the University of Pennsylvanias Perelman School of Medicine. You can prevent yourself from being infected as well as transmitting to others.

According to the CDC, you should wet your handsfront and backwith clean, running water; lather up with soap, paying mind to the easily-forgotten spaces between your fingers and beneath your nails; scrub for at least 20 seconds; then rinse and dry. (Pro tip: If counting bores you or youre sick of the birthday song, try the chorus of these popular songs to keep track.)

Done properly, this process accomplishes several virus-taming tasks. First, the potent trifecta of lathering, scrubbing and rinsing physically removes pathogens from your skin, says Shirlee Wohl, a virologist and epidemiologist at Johns Hopkins University.

In many ways, soap molecules are ideal for the task at hand. Soap can incapacitate SARS-CoV-2 and other viruses that have an outer coating called an envelope, which helps the pathogens latch onto and invade new cells. Viral envelopes and soap molecules both contain fatty substances that tend to interact with each other when placed in close proximity, breaking up the envelopes and incapacitating the pathogen. Basically, the viruses become unable to infect a human cell, Permar says.

Alcohol-based hand sanitizers also target these vulnerable viral envelopes, but in a slightly different way. While soap physically dismantles the envelope using brute force, alcohol changes the envelopes chemical properties, making it less stable and more permeable to the outside world, says Benhur Lee, a microbiologist at the Icahn School of Medicine at Mount Sinai. (Note that alcohol here means a chemical like ethanol or isopropyl alcoholnot a beverage like vodka, which contains only some ethanol.)

Alcohol also can penetrate deep into the pathogens interior, wreaking havoc on proteins throughout the virus. (Importantly, not all viruses come with outer envelopes. Those that dont, like the viruses that cause HPV and polio, wont be susceptible to soap, and to some extent alcohol, in the same way.)

Hand sanitizers made without alcohollike some marketed as baby-safe or naturalwont have the same effect. The CDC recommends searching for a product with at least 60 percent alcohol contentthe minimum concentration found to be effective in past studies. (Some water is necessary to unravel the pathogens proteins, so 100 percent alcohol isnt a good option.)

As with hand-washing, timing matters with sanitizers. After squirting a dollop onto your palm, rub it all over your hands, front and back, until theyre completely drywithout wiping them off on a towel, which could keep the sanitizer from finishing its job, Jurado says.,

But hand sanitizers come with drawbacks. For most people, using these products is less intuitive than hand-washing, and the CDC notes that many people dont follow the instructions for proper application. Hand sanitizers also dont jettison microbes off skin like soap, which is formulated to lift oily schmutz off surfaces, Akusobi says.

Soap emulsifies things like dirt really well, he says. When you have a dirty plate, you dont want to use alcoholthat would help sterilize it, but not clean it.

Similarly, anytime the grit is visible on your hands, dont grab the hand sanitizer; only a full 20 seconds (or more) of scrubbing with soapy water will do. All told, hand sanitizer should not be considered a replacement for soap and water, Lee says. If I have access to soap and water, I will use it.

Technically, it is possible to overdo it with both hand-washing and hand sanitizing, Akusobi says. If your skin is chronically dry and cracking, thats no good. You could be exposing yourself to other infections, he says. But it would take a lot to get to that point.

In recent weeks, hand sanitizers have been flying off the shelves, leading to shortages and even prompting some retailers to ration their supplies. Some people have begun brewing up hand sanitizers at home based on online recipes.

Many caution against this DIY approach, as the end products cant be quality controlled for effectiveness, uniformity or safety, says Eric Rubin, an infectious disease researcher at Harvards School of Public Health. On average, one would imagine that [a homemade sanitizer] would not work as well, so it would be a mistake to rely on it, he says.

As more information on SARS-CoV-2 and COVID-19 emerges, experts stress the importance of awareness. Even as the news changes and evolves, peoples vigilance shouldnt.

Do the small things you need to do to physically and mentally prepare for whats next, Wohl says. But dont panic. That never helps anybody.

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Why Is Washing Your Hands So Important Anyway? - Smithsonian

Recommendation and review posted by Bethany Smith

A new population of stem cells that can generate bone has been revealed by researchers, which they say could have implications in regenerative medicine.

A population of stem cells with the ability to generate new bone has been newly discovered by a group of researchers at the University of Connecticut (UConn) School of Dental Medicine, US.

The researchers present a new population of cells that reside along the vascular channels that stretch across the bone and connect the inner and outer parts of the bone.

This is a new discovery of perivascular cells residing within the bone itself that can generate new bone forming cells, said lead investigator Dr Ivo Kalajzic. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

Stem cells for bone have long been thought to be present within bone marrow and the outer surface of bone, serving as reserve cells that constantly generate new bone or participate in bone repair. Recent studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow, but no research has proved the existence of cells within these channels that have the ability to form new bones.

In this study, Kalajzic and his team are the first to report the existence of these progenitor cells within cortical bone that can generate new bone-forming cells osteoblasts that can be used to help remodel a bone.

To reach this conclusion, the researchers observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant and began to reconstruct the marrow cavity and form new bone.

While this study shows there is a population of cells that can help aid formation, more research needs to be done to determine the cells potential to regulate bone formation and resorption, say the scientists.

According to the authors of the study: we have identified and characterised a novel stromal lineagerestricted osteoprogenitor that is associated with transcortical vessels of long bones. Functionally, we have demonstrated that this population can migrate out of cortical bone channels, expand and differentiate into osteoblasts, therefore serving as a source of progenitors contributing to new bone formation.

The results are published inSTEM CELLS.

The rest is here:
Stem cells that can grow new bone discovered by researchers - Drug Target Review

Recommendation and review posted by Bethany Smith

Stem cell research has been the subject of discussion and heated debate for many years. Much of the social and political drama surrounding stem cells is the result of misunderstanding what stem cells are, where they come from, and what they can do for those with injuries and diseases.

Working from a common set of facts is a great way to dispel controversy, however. Whether we fall into the pro-choice or pro-life camp, it is more than evident that supporting stem cell research, including the development of stem cell therapies, is very much a pro-life position to take.

Stem cells function essentially like raw materials for the body. Depending on instructions from the body (or researchers in laboratories), stem cells can become many other types of cells with specialized functions.

The daughters of stem cells either become new stem cells (self-renewal) or they become more specialized cells for use in specific areas of the body (differentiation). These specialized cells include brain cells, heart muscle cells, bone cells, blood cells and others.

There are several reasons why stem cells are the focus of some of the most important medical science research today:

This last avenue of medical research stem cell therapies is the most consequential as well as the most controversial, depending on your point of view. Understanding stem cell therapy and its divisiveness requires understanding where stem cells come from in medical research and why they have considerable palliative potential.

Stem cells come from one of these three sources:

Embryonic stem cells are the most controversial as well as the most important type of stem cells right now. Thanks to a low-information electorate and gross misinformation from within the government, embryonic stem cells remain mired in needless debate.

Despite the rhetoric, these cells arent harvested from slain newborns. Instead, they are carefully gathered from blastocysts. Blastocysts are three-to-five-day-old embryos comprised of around 150 cells. According to some religious-political arguments, blastocysts are potential human beings, and therefore deserve legal protection.

Embryonic stem cells are the most valuable in medical research because they are fully pluripotent, which means they are versatile enough to become any type of cell the body requires to heal or repair itself.

Adults have limited numbers of stem cells in a variety of bodily tissues, including fat and bone marrow. Unlike pluripotent embryonic stem cells, adult stem cells have more limits on the types of cells they can become.

However, medical researchers keep uncovering evidence that adult stem cells may be more pliable than they originally believed. There is reason to believe cells from adult bone marrow may eventually help patients overcome heart disease and neurological problems. However, adult stem cells are more likely than embryonic stem cells to show abnormalities and environment-induced damage, including cell replication errors and toxins.

The newest efforts in stem cell research involve using genetic manipulation to turn adult stem cells into more versatile embryonic variants. This could help side-step the thorny abortion controversy, but its also not clear at present whether these altered stem cells may bring unforeseen side-effects when used in humans.

More research is required to fully understand the medical potential of perinatal stem cells. However, some scientists believe they may in time become a viable replacement for other types of stem cells. Perinatal stem cells come from amniotic fluid and umbilical cord blood.

Using a standard amniocentesis, doctors can extract umbilical cord mesenchymal stem cells, hematopoietic stem cells, amniotic membrane and fluid stem cells, amniotic epithelial cells and others.

Among other things, stem cell therapy is the next step forward for organ transplants. Instead of waiting on a transplant waiting list, patients may soon be able to have new organs grown from their very own stem cells.

Bone marrow transplants are one of the best-known examples of stem cell therapy. This is where doctors take bone marrow cells and induce them to become heart muscle cells.

Stem cell-based therapies hold significant promise across a wide range of medical conditions and diseases. With the right approach, stem cells show the potential to:

As the FDA notes, there is a lot of hype surrounding stem cell therapy. Much of it is warranted, but some of it deserves caution.

According to the FDA, stem cells have the potential to treat diseases or conditions for which few treatments exist. The FDA has a thorough investigational process for new stem cell-based treatments. This includes Investigational New Drug Applications (IND) and conducting animal testing.

However, the FDA notes that not every medical entity submits an IND when they bring a new stem cell therapy to market. It is vital that patients seek out only FDA-reviewed stem cell therapies and learn all they can about the potential risks, which include reactions at the administration site and even the growth of tumors.

The FDA submitted a paper, Clarifying Stem-Cell Therapys Benefits and Risks, to the New England Journal of Medicine in 2017. Its goal is to help patients fully understand what theyre getting themselves into.

For now, a great deal more research is required before we begin deploying stem cell therapies on a larger scale. The only FDA-approved stem cell therapies on the market today involve treating cancer in bone marrow and blood. Some clinics claim their therapy delivers miracle-like cures for everything from sports injuries to muscular dystrophy, but there just isnt enough evidence yet to take them at face value.

Unfortunately, the religious and political climate makes this evidence difficult to achieve. In some parts of the United States, the hostility toward stem cell researchers and medical practitioners has reached dangerous new levels.

Republicans in Ohio and Georgia want to make it illegal for doctors to perform routine procedures on ectopic pregnancies. This condition is life-threatening for the mother and involves the removal of a nonviable embryo from the fallopian tube.

These laws wouldnt just outlaw ectopic pregnancy surgery in the name of potential human life. It would, in fact, require women to undergo a reimplantation procedure after the ectopic pregnancy is corrected by a physician. If this procedure was actually medically possible, it would be dangerous and unnecessary. Thankfully, it doesnt exist outside the nightmarish imaginations of some of the more extreme Christian lawmakers and Planned Parenthood demonstrators.

Acquiring embryonic stem cells from ectopic pregnancies would seem to be the least controversial way to go about it. Unfortunately, even that small step toward medical progress sees itself hampered by reactionary politics.

No matter how theyre acquired, however, the 150 or so cells in blastocysts are packed with medical potential. Its clear that further exploration down this road will unlock unprecedented scientific progress. It will also, almost certainly, save many times more potential life than even the most outlandish estimates of what the achievement will cost us to achieve. Abortions today are rarer and safer than ever, and the vast majority occur within eight weeks of conception.

The medical community is poised for a revolution here, using these and other nonviable embryos and blastocysts. But realizing that potential requires, among other things, that we collectively make peace with modern medicine and family planning.

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Despite Pro-Life Claims, Stem Cell Therapy Has Very Real Benefits and Should Be Accessible - Patheos

Recommendation and review posted by Bethany Smith

Steven Hodi Jr., the i3 Centers other PI, and director of Melanoma Center and the Center for Immuno-Oncology at Dana-Farber, and professor of medicine at Harvard Medical School (HMS), is leading the clinical cancer vaccine trial. He has been at the forefront of developing cancer immunotherapies using immune checkpoint inhibitors, a class of drugs able to re-activate tumor-destroying T cells that are muted in the tumor microenvironment. The funding for this center provides a unique opportunity to unite key investigators for translating fundamental advancements in immunology and biomedical engineering into highly synergistic approaches to improve the treatments for cancer patients, said Hod

Using both in vivo and ex vivo biomaterials-based approaches, the i3 Center aims to boost tumor-specific activities of cytotoxic T cells, by boosting different stages of the normal process by which T cells develop, and acquire anti-cancer activity. T cells normal development starts in the bone marrow where hematopoietic stem cells generate T cell progenitor cells. These migrate to the thymus to differentiate into nave T cells, which then travel further to lymph nodes. There, they encounter cancer-derived antigens presented to them by specialized antigen-presenting cells (APCs) that can activate T cells to recognize and eliminate cancer cells.

In relation to adoptive T cell therapies in which T cells are given to patients to fight their cancers, one team at the i3 Center will be led by Dana-Farber researchers Catherine J. Wu and Jerome Ritz, who along with Mooney, will develop and test biomaterials that can better mimic normal APCs in activating and directing the function of patient-derived T cells outside the human body, prior to their transplantation. Wu is chief of the Division of Stem Cell Transplantation and Cellular Therapies, and Ritz is executive director of the Connell and OReilly Families Cell Manipulation Core Facility at Dana-Farber.

We need to make efforts to enhance the ability of theimmune systemto recognizetumor cells. One directionmylaboratoryis taking makes use of innovative biomaterialsto help us to efficiently expandpolyclonaltumor-specificfunctionally-effectiveT cellsex vivoin a way that can be readily translated to theclinical setting. In our studies, we are currently focusing on melanoma and acute myeloid leukemia, said Wu, whose research interests include understanding the basis of effective human anti-tumor responses, including the identification and targeting of the tumor-specific antigens.

A second project explores the use of DNA origami, biocompatible nanostructures composed of DNA, to create cancer vaccines. DNA origami could provide significant advantages in presenting tumor-specific antigens and immune-enhancing adjuvants to APCs because the concentrations, ratios, and geometries of all components can be modulated with nano-scale precision to determine configurations that are more effective than other vaccination strategies. The project will be run by Wyss Institute Core Faculty member William Shih, Derin Keskin, lead immunologist at Dana-Farbers Translational Immunogenomics Lab, and Mooney.

In a third project, David Scadden, professor at Harvards Department of Stem Cell and Regenerative Biology, will collaborate with Mooney to build on their previous work. They will engineer biomaterials that recreate key features of the normal hematopoietic stem cell niche in the bone marrow. Such implantable biomaterials could help rapidly amplify T cell progenitor cells, and enhance T cell-mediated anti-cancer immunity. Scadden also is the Gerald and Darlene Jordan Professor of Medicine at Harvard University, and co-director of the Harvard Stem Cell Institute.

The i3 Centers investigators anticipate that it will stimulate additional cross-disciplinary concepts and research, due to the culture of continuous interactions, sharing of findings, data and samples between all investigators, as well strong biostatistical expertise provided by Donna Neuberg, a senior biostatistician broadly involved with exploring immune-modulating cancer interventions at the Dana-Farber.

This new i3 Center for cancer immunotherapy innovation really embodies how the Wyss Institute with its unparalleled capabilities in bioengineering and serving as a site for multidisciplinary collaboration, and can liaise with clinicians and researchers at our collaborating institutions to confront major medical problems and bring about transformative change, said Wyss Founding Director Donald Ingber. He is also theJudah Folkman Professor of Vascular Biologyat HMS and the Vascular Biology Program at Boston Childrens Hospital, and Professor of Bioengineering at SEAS.

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NIH-funded i3 Center formed to advance cancer immunotherapy - Harvard Gazette

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Researchers from UConn School of Dental Medicine have recently discovered a group of stem cells that help in generating a new bone. In regards with this, Dr Ivo Kalajzic, professor of reconstructive sciences, stated that, this newly discovered perivascular stem cells that reside in the bone itself have capability of generating the bone and these cells are highly instrumental in repair & mass maintenance of the bone along with its formation.

Since ages, it has been thought that stem cells only reside in bone marrow and exterior surface of the bone stores the cells that continuously generate new bone or repair the bone. Postdoctoral individuals Dr Sierra Root and Dr Natalie Wee, and collaborators at Harvard, Maine Medical Research Center, and the University of Auckland also were part of this study along with Dr Ivo Kalajzic and confirmed that these new cluster of cells residing in the vascular channels that range across the bone and serve as connection between inner and outer part of the bone is capable of generating a new bone.

This team is also pioneer in bringing forward a study that says existence of these progenitor cells inside cortical bone not only generates a new bone but also help remodeling of the bone. The conclusion was made after these researchers observed that these stem cells within an ex vivo bone transportation model migrated out of the transplant and started manufacturing a new bone marrow cavity along with completely new bone.

In order to establish this, more research needs to done as it will definitely turn out wonderful to the field of medical science and mankind.

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Stem Cells that will aid new bone generation discovered as per latest research - Medical Herald

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Two-year-old Regann Moore lights up as she watches videos on her iPad at home on Thursday, Feb. 20, 2020. Moore has a rare disease known as Krabbe Disease and received a life-saving stem cell donation less than a month after being born.(Photo: Nathan Papes/Springfield News-Leader)

Soon after the News-Leader published a story about 2-year-old Regann Moore,a Springfield child whose life was saved thanks to a newborn screening test, someone tweeted the story toMissouri State Rep. Becky Ruth.

"I bawled my eyes out," Ruth said. "I just cried."

She cried because she knew Regann is alive thanks to the death of Ruth's grandson, Brady.

"I cry and smile when I see these children," Ruth said. "We are always so thankful. For us, we see Brady's death wasn't in vain. His legacy lives on by helping save the lives of other children."

More: Springfield child with rare, deadly disease continues to amaze doctors, family

Regann, who is 2 now, was diagnosed right after she was born withKrabbe Disease, a rare metabolic disorder that must be diagnosed at birth and treated as soon as possible with a stem cell donation.

The newborn screening is important because babies with Krabbe Disease appear healthy at birth. Signs something is wrong usually don't appear until it's too late for treatment to be effective.

That is what happened to Brady in 2009. He wasn't diagnosed with the disease until he was 4.5 months old too late for treatment.

Brady died 10 days before his first birthday.

Brady Cunningham died of Krabbe Disease just before his first birthday.(Photo: Courtesy of the Cunningham family)

That's why Ruth and her family fought to get lawmakers on board with making sure all newborns in Missouri are screened for Krabbe Disease.

TheBrady Alan Cunningham Newborn Screening Act was passed in 2009 and screening began in 2012. Ruthsaid her family was OK with the three-year lag because they realized the lab needed time to become equipped to test for the disease.

Missouri is one of just a few states that do the newborn screening.

Brady's law also includes screening for Pompe, Fabry, Gauche and Niemann-Pick diseases. Since then, SCID, MPS I, MPS II and SMA diseases are screened, as well.

Ruth became a state representative in 2015and said newborn screening is her passion.

Her experience with getting Brady's law passed is what led her to seek office.

"It showed me what just a regular everyday person can do and what a differenceyou can make," Ruth said. "People a lot of times complain about politicians and the legislature, but we also do very good things here."

Ruth said her family knows of another child with Krabbe Disease who was saved thanks to newborn screening and a stem cell transplant.

That child is now 4. Ruth said her family and that child's family have a "strong connection."Ruth said shehopes to someday meet Regann's family.

Brady Cunningham was born in 2008. His family is from Campbell in southeast Missouri.

Bradyappeared healthy at birth and was not tested for Krabbe Disease.

Ruth said he started having health problems after about a month and a half. Brady went through "a myriad of diagnoses," Ruth recalled, including acid reflux and seizures.

"Finally my daughter took him to Children's Hospital in St. Louis," she said. "They promised her he wouldn't leave without a diagnosis."

Missouri State Rep. Becky Ruth was moved to tears after reading about Regann Moore, a Springfield child whose life was saved thanks to newborn screening for Krabbe Disease. Ruth and her family encouraged Missouri lawmakers to make sure all Missouri babies are tested for the deadly disease after her grandson, Brady, died from it.(Photo: Submitted by Becky Ruth)

Three weeks later, Brady was diagnosed with Krabbe Disease, which rapidly destroys the nervous system.

"We were told there was nothing they could do," she said. "It was one of the worst days of all of our lives."

Brady was 4.5 months old when he was diagnosed. In order for a stem cell donation to have any chance of being effective, babies must have the transplant within the first month of their life.

Regann, the Springfield child, was given a stem cell donation thanks to an umbilical cord donation.

Thediseaseaffects about one in every 100,000 people in the United States.

"They are missing an enzyme that helps keep their nervous system intact," said Dr. Shalini Shenoy, Regann's transplant doctor. "Because this is missing, they have degeneration of the brain and nervous system. And if you let it progress, it is fatal very early."

Without the stem cell donation, babies die within the first few months, Shenoy said.

"You can't change someone's genetic makeup," Shenoy said. "But when you put stem cells into their bone marrow from somebody else who is normal, some of these cells migrate into their brain and into their nervous system and supply what they are lacking themselves."

It takes some time for the transplant to begin working for the transplanted cells to "settle down" and begin making the missing enzyme, Shenoy said.

"Because of that, the earlier you transplant a Krabbe patient, the more you will be able to rescue them," she said. "You want to catch them before too much damage is done. Once there's a lot of nerve damage, it's not reversible. If I saw a Krabbe patient two months after they were born or four months after they were born when they already had major problems, it's unlikely I'd be able to rescue them too much."

Since the screening and the stem cell transplant treatment are both relatively recent medical advancements, Shenoy said it's anybody's guess what the future will hold for children who, like Regann, were successfully treated with a stem cell transplant early on.

Ferrell Moore holds his two-year-old daughter Regann Moore at their home on Thursday, Feb. 20, 2020. Regann has a rare disease known as Krabbe Disease and received a life-saving stem cell donation less than a month after being born.(Photo: Nathan Papes/Springfield News-Leader)

Regann can't stand on her own or walk yet. But her family is determined to make that happen. She cannot talk but is learning sign language to communicate.

She has regular visits with speech and occupational therapists.

Regann's dad Ferrell Moore got to take her to the circus recently, something the little girl seemed to enjoy.

"She is the joy of my life," Ferrell Moore said. "When I come home, it couldn't be any better to see her and how happy she is to see me."

Read or Share this story: https://www.news-leader.com/story/news/local/ozarks/2020/03/05/grandma-who-helped-pass-newborn-screening-law-tells-story-bill/4954655002/

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'His legacy lives on': Grandmother who helped create newborn screening law tells history of bill - News-Leader

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