2018 is supposed to be the year of CRISPR in humans. The first U.S. and European clinical trials that test the gene-editing tool's ability to treat diseasessuch as sickle-cell anemia, beta thalassemia, and a type of inherited blindnessare slated to begin this year.

But the year has begun on a cautionary note. On Friday, Stanford researchers posted a preprint (which has not been peer reviewed) to the website biorXiv highlighting a potential obstacle to using CRISPR in humans: Many of us may already be immune to it. Thats because CRISPR actually comes from bacteria that often live on or infect humans, and we have built up immunity to the proteins from these bacteria over our lives.

Its the first time this concern has been aired so publicly, and the preprint kicked off something of a firestorm. We had no anticipation it would be picked up so broadly on social media. I dont even have a Twitter account. I just heard this from others, says Matthew Porteus, a pediatrician and stem-cell researcher at Stanford who led the study and is working on a clinical trial for sickle-cell anemia.

Not all CRISPR therapies in humans will be doomed. We dont think this is the end of the story. This is the start of the story, says Porteus. There are likely ways around the problem of immunity to CRISPR proteins, and many of the early clinical trials appear to be designed around this problem.

Porteus and his colleagues focused on two versions of Cas9, the bacterial protein mostly commonly used in CRISPR gene editing. One comes from Staphylococcus aureus, which often harmlessly lives on skin but can sometimes causes staph infections, and another from Streptococcus pyogenes, which causes strep throat but can also become flesh-eating bacteria when it spreads to other parts of the body. So yeah, you want your immune system to be on guard against these bacteria.

The human immune system has a couple different ways of recognizing foreign proteins, and the team tested for both. First, they looked to see if people have molecules in their blood called antibodies that can specifically bind to Cas9. Among 34 people they tested, 79 percent had antibodies against the staph Cas9 and 65 percent against the strep Cas9.

Then, they looked to see if a particular type of immune cells called T cells can recognize the Cas9 proteins. This time they studied T cells from 13 healthy adults. Six of themor 46 percentreacted to the staph Cas9. None of them did against the strep Cas9.

The Stanford team only tested for preexisting immunity against Cas9, but anytime you inject a large bacterial protein into the human body, it can provoke an immune response. After all, thats how the immune system learns to fight off bacteria its never seen before. (Preexisting immunity can make the response faster and more robust, though.)

In statements to The Atlantic, three of the leading companies in CRISPR human therapyEditas Medicine, CRISPR Therapeutics, and Intellia Therapeuticsall downplayed the new findings, citing various ways their therapies could around the immune system. (Porteus is a scientific founder of CRISPR Therapeutics, though this study was performed independently.) A September 2017 presentation from a scientist at Editas Medicine also detailed some of the ways to test for immune reactions to CRISPR, anticipating a potential problem.

Here are some possible strategies to get around the immune system that are being discussed and tested:

Only use CRISPR outside of the body: Instead of delivering CRISPR/Cas9 into the body, you take cells out of the body, use CRISPR to edit their genes in a lab, and return Cas9-free cells. This is the strategy pursued by CRISPR Therapeutics for the inherited blood disorder thalassemia and in various trials using CRISPR to modify immune cells to attack cancer.

Only use CRISPR in places the immune system cannot reach: Some sites of the body are immunoprivileged, meaning the immune system cant really attack invaders there. The eye, which Editas Medicine is targeting for inherited blindness, is one of those sites.

Modify Cas9 or use a different CRISPR protein altogether: It may be possible to redesign Cas9 to hide it from the immune system or to find other bacterial proteins that can do the job of Cas9 without provoking the immune response. Many different bacteria have CRISPR systems. We already have lots of Cas enzymes and could get many more, George Church, a geneticist at Harvard and a founding scientific advisor of Editas, wrote in an email.

Express Cas9 only transiently:Once Cas9 has made its edit, it doesnt need to stick around. A spokesperson for Intellia noted that its still unclear how the immune system responds to continuous versus transient expression of Cas9. The company says its lipid-nanoparticle delivery system can get cells to make Cas9 only transiently, but enough for the editing to happen in rodents and non-human primates.

The one type of therapy where immune response may be most dangerous and unavoidable is when Cas9 is produced for a prolonged period of time in a non-immunoprivileged site. In the liver, for instance, the immune system could end up attacking the Cas9-making liver cells.

The danger of the immune system turning on a patients body hangs over a lot of research into correcting genes. In the late 1990s and 2000s, research into gene therapy was derailed by the death of 18-year-old Jesse Gelsinger, who died from an immune reaction to the virus used to deliver the corrected gene. This is the worst-case scenario that the CRISPR world hopes to avoid.

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Obstacle to Using CRISPR in Humans? The Immune System - The ...

Recommendation and review posted by sam

Many women are unable to conceive and deliver a healthy baby due to genetic factors. Sometimes this is due to an inherited chromosome abnormality. Other times it is because of a single-gene defect passed from parent to child.

In addition, if other women in your family have had problems conceiving due to premature menopause, endometriosis or other factors, you may be at increased risk of the same problems.

Chromosomally abnormal embryos have a low rate of implantation in the mothers uterus, often leading to miscarriages. If an abnormal embryo does implant, the pregnancy may still result in miscarriage or the birth of a baby with physical problems, developmental delay, or mental retardation.

There are several kinds of chromosome abnormalities:

Translocation is the most common of these. Although a parent who carries a translocation is frequently normal, his or her embryo may receive too much or too little genetic material, and a miscarriage often results.

Couples with specific chromosome defects may benefit from pre-implantation genetic diagnosis (PGD) in conjunction with in vitro fertilization (IVF).

Down syndrome is usually associated with advanced maternal age and is a common example of aneuploidy. Down syndrome is caused by having an extra number-21 chromosome (three instead of two). It is also referred to as trisomy 21.

More rare is the existence of an inherited genetic disease due to abnormal genes or mutations. Chromosome analysis of the parents blood identifies such an inherited genetic cause in less than 5 percent of couples.

Single-gene abnormalities are mutations caused by changes in the DNA sequence of a gene, which produce proteins that allow cells to work properly. Gene mutations alter the functioning of cells due to a lack of a protein.

Single-gene disorders usually indicate a family history of a specific genetic disease such as cystic fibrosis (CF) an incurable and fatal disease affecting the mucous glands of vital organs and Tay Sachs, also a fatal disorder, in which harmful quantities of a fatty substance build up in tissues and nerve cells in the brain.

Though generally rare, these diseases are usually devastating to a family. Fortunately, much progress has been made in detection through pre-implantation genetic diagnosis (PGD) in conjunction with in vitro fertilization (IVF).

Although a couple may otherwise have no fertility problems, IVF and PGD can work together to spare mother and father from heartache in cases where there is a known single-gene family history.

Learn more about genetic causes of infertility

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Is Infertility Genetic? | Female Infertility Genetic ...

Recommendation and review posted by simmons

Certain diseases and treatments can deplete a child's healthy stem cells. Sometimes the body needs help to replenish those cells. When this happens, your child may require a very complex process called a stem cell or bone marrow transplant.

Since 1986, Cook Children's Bone Marrow and Stem Cell Transplant program has performed more than 1,000 transplants in children with cancer, blood disorders or inherited conditions. That's what makes this program one of the more diverse and experienced pediatric transplant programs in the Southwest.

Cook Children's is a member of:

Over the last three years, 30 to 40 transplants were performed every year for a variety of diseases, with leukemia being the most common primary diagnosis.

The goal of the program is to provide a stem cell or marrow transplant to any child who needs one and to improve the outcomes for these patients who do not have better therapy options. We work to achieve this goal through excellent clinical care from several services within Cook Children's, quality initiatives and ongoing comparison of our processes and performance against large academic transplant centers and international data.

Common referral diagnoses:

Stem cells are cells in the body that have the potential to turn into anything, such as a skin cell, a liver cell, a brain cell, or a blood cell. Stem cells that turn into blood cells are called hematopoietic stem cells. These cells are capable of developing into the three types of blood cells:

Stem cells may come from the patient or from a donor. Stem cells that come from a patient may come from their own cord blood cells if they were harvested from the mother's placenta immediately after the child was born and frozen for later use. Stem cells may also be harvested and frozen before the child or teen undergoes treatment. These stem cells are thawed and put back into the patient's body after treatment is complete.

Donor stem cells come from a compatible family member or through a match from a national registry of donors. Depending on the particular needs of your child, one or all three types of a donor's stem cells will be harvested:

While all three types can replenish a patient's blood and bone marrow cells, there are advantages and disadvantages to each. The doctor will discuss these issues and suggest the best type of stem cell for your child's illness.

If your child has been diagnosed, you probably have lots of questions. We can help. If you would like to schedule an appointment, refer a patient or speak to our staff, please call our offices at 682-885-4007.

See more here:
Bone Marrow and Stem Cell Transplant | Cook Children's

Recommendation and review posted by Bethany Smith

As their name suggests, embryonic stem cells (ESCs) are stem cells that are derived from embryos. If we wanted to be more scientific, we would say that ESCs are pluripotent stem cells derived from a blastocyst, an embryo in a very early stage (4-5 days of age).A blastocyst is consisted of 50-150 cells. ESCs measure approximately 14m in diameter.

The use of human embryonic stem cells is highly controversial, as their extraction requires the destruction of a human embryo, raising a great number of ethical issues. The main one is whether a blastocyst can be considered a living person or not. Check our article, Stem Cell Controversy for more info on this topic

Embryonic Stem cell propertiesThere are two important attributes that distinguish stem cells from any other typical cell:

Embryonic stem cells are pluripotent, having the capacity to differentiate and develop into almost all kinds of cells belonging to thethree primary germ layers:

As for self-renewal, ES cells have the capacity to replicate indefinitely. In other words they have the ability, under the proper conditions, to produce infinite numbers of daughter cells just from one or a few father cells.

Human Embryonic Stem Cell Extraction And CultureFirst the inner cell mass (ICM) of the blastocyst is separated from the trophectoderm. Then the cells of the ICM are placed on aplastic laboratory culture dish that contains a nutrient broth called the "culture medium".Typically the inner surface of the dish is coated with what is called a "feeder layer", consisting of reprogrammed embryonic mouse skin cells that don't divide. These mouse cells lay in the bottom of the dish and act as a support for the hESCs. The feeder layer not only provides support, but it also releases all the needed nutrients for thehESCs to grow and replicate. Recently, scientists have devised new ways for culturing hESCs without the need of a mouse feeder cell, a really important advance as there is always the danger of viruses being transmitted from the mouse cells to the human embryonic stem cells.

It should be noted that the process described above isn't always successful, and many times the cells fail to replicate and/or survive. If on the other hand, the hESCs do manage to survive and multiply enough so that the dish is "full", they have to be removed and plated into several dishes. This replating and subculturing process can be done again and again for many months. This way we can get millions and millions of hESCs from the handful ones we had at the beginning.

At any stage of the process, a batch of hESCs can be frozen for future use or to be sent somewhere else for further culturing and experimentation.

How are human embryonic stem cells induced to differentiate ?There are various options for researchers to choose from, if they decide to differentiate the cultured cells.

The easiest one, is to simply allow the cells to replicate until the disc is "full". Once the disc is full, they start to clump together forming embryoid bodies(rounded collections of cells ). These embryoid bodies contain all kinds of cells including muscle, nerve, blood and heart cells. As said before, although this is easiest method to induce differentiation, it is the most inefficient and unpredictable as well.

In order to induce differentiation to a specific type of cell, researchers have to change the environment of the dish by employingone of the ways below:

Human Embryonic Stem Cells, potential usesMany researchers believe that studying hESCs is crucial for fully understanding the complex events happening during the fetal development. This knowledge would also include all the complex mechanisms that trigger undifferentiated stem cells to develop into tissues and organs. A deeper understanding of all these mechanisms would in return give scientists a deeper understanding of what sometimes goes wrong and as a result tumours,birth defects and other genetic conditions occur, thus helping them to come up with effective treatments.

Several new studies also address the fact that human embryonicstem cells can be used as models for human genetic disorders that currently have no reliable model system. Two examples are the Fragile-X syndromeandCystic fibrosis.

As of now, there has been only one human clinical trial ,involving embryonic stem cells, with the officialapproval of the U.S. Food and Drug Administration (FDA).The trial started on January 23, 2009, and involved the transplantation ofoligodendrocytes (a cell type of the brain and spinal cord) derived from human embryonic stem cells. During phase I of the trial, 8 to 10paraplegics with fresh spinal cord injuries (two weeks or less) were supposed to participate.

In August 2009,the trial wasput on hold, due to concerns made by the FDA, regarding a small number of microscopic cysts found in several treated rat models. InJuly 30, 2010 the hold was lifted and researchers enrolled the first patient and administered him with the stem cell therapy.

Read the original here:
Embryonic Stem Cells | Stem Cells Freak

Recommendation and review posted by Bethany Smith

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used. To access online sources, copy and paste the URL into your browser.

Sources Used in Current Review

American Brain Tumor Association. 2014. Craniopharyngioma. Available online at http://www.abta.org/brain-tumor-information/types-of-tumors/craniopharyngioma.html. Accessed April 2, 2017.

Cleveland Clinic Center for Continuing Education. 2012. Pituitary Disorders. Available online at http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/pituitary-disorders/. Accessed April 2, 2017.

Goldberg J., and Jewell, T. 2016. Prolactin Level Test. Healthline. Available online at http://www.healthline.com/health/prolactin#overview1. Accessed March 31, 2017.

Hormone Health Network. 2012. Cushing Syndrome. Available online at http://www.hormone.org/diseases-and-conditions/adrenal/cushing-syndrome. Accessed April 2, 2017.

Hormone Health Network. 2013. Diabetes Insipidus. Available online at http://www.hormone.org/diseases-and-conditions/pituitary/diabetes-insipidus. Accessed April 2, 2017.

Hormone Health Network. 2012. Acromegaly. Available online at http://www.hormone.org/diseases-and-conditions/pituitary/acromegaly. Accessed April 2, 2017.

National Organization for Rare Disorders. 2013. Empty Sella Syndrome. Available online at https://rarediseases.org/rare-diseases/empty-sella-syndrome/. Accessed April 2, 2017.

Pituitary Network Association. 2013. Disorders. Available online at http://pituitary.org/knowledge-base/disorders. Accessed March 29, 2017.

Pituitary Network Association. 2013. Adrenal Insufficiency (Addison's Disease). Available online at http://pituitary.org/knowledge-base/disorders/adrenal-insuffieciency-addison-s-disease. Accessed April 7, 2017.

Sources Used in Previous Reviews

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

(2003 February 1, Revised). Introduction. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162a.html.

(2003 February 1, Revised). Acromegaly and Gigantism. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162e.html.

(2003 February 1, Revised). Central Diabetes Insipidus. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162d.html.

Empty Sella Syndrome (2003 February 1, Revised). Empty Sella Syndrome. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162g.html.

Galactorrhea (2003 February 1, Revised). Galactorrhea. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162f.html.

(2003 February 1, Revised). Hypopituitarism. The Merck Manual of Medical Information Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch162/ch162c.html.

Leung, A. and Pacaud, D. (2004 August 1). Diagnosis and Management of Galactorrhea. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20040801/543.html.

(2005 April). Diabetes Insipidus. FamilyDoctor.org [On-line information]. Available online at http://familydoctor.org/048.xml.

Klibanski, A., Editor (2004 January, Reviewed). Pituitary Information. The Hormone Foundation [On-line information]. Available online at http://www.hormone.org/learn/pituitary.html.

( 2004). The Pituitary Foundation. Fact Sheets [On-line information]. Available online at http://www.pituitary.org.uk. For: Cushing's Disease, Non-Functioning Pituitary Tumours, Acromegaly, Hyperprolactinaemia, Craniopharyngioma, Hypopituitarism, Diabetes Insipidus

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 353-356.

Klibanski, A. Editor (2008 March)Pituitary) Pituitary Gland. The Hormone Foundation [On-line information]. Available online at http://www.hormone.org/pituitary_gland.cfm. Accessed on 1/4/09.

Principles of Endocrinology, Introduction. The Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec12/ch150/ch150a.html. Accessed on 1/4/09.

Principles of Endocrinology, Endocrine Disorders. The Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec12/ch150/ch150b.html. Accessed on 1/4/09.

Mayo Clinic Staff (2008 June 6). Pituitary Tumors. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/pituitary-tumors/DS00533. Accessed on 1/4/09.

(2008 August, Revised). Pituitary Disorders. Pituitary Network Association [On-line information]. Available online at http://www.pituitary.org/disorders/. Accessed on 1/4/09.

(2007 September 5, Updated). NINDS Pituitary Tumors Information Page. National Institute of Neurological Disorders and Stroke [On-line information]. Available online at http://www.ninds.nih.gov/disorders/pituitary_tumors/pituitary_tumors.htm. Accessed on 1/4/09.

Kattah, J. (2006 March 30). Pituitary Tumors. EMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1157189-overview. Accessed on 1/4/09.

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pp. 1481-1483.

I. Jialaal, W. E. Winter, and D.W. Chan (eds). Handbook of Diagnostic Endocrinology, AACC Press, 1999.

(Reviewed April 2009). Principles of Endocrinology, Endocrine Disorders. The Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec12/ch150/ch150a.html. Accessed on October 12, 2012

Mayo Clinic Staff. (Updated August 10, 2012). Pituitary Tumors. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/pituitary-tumors/DS00533. Accessed on October 12, 2012.

(Updated October 26, 2010). NINDS Pituitary Tumors Information Page. National Institute of Neurological Disorders and Stroke [On-line information]. Available online at http://www.ninds.nih.gov/disorders/pituitary_tumors/pituitary_tumors.htm. Accessed on October 12, 2012.

(Updated August 15, 2011). Pituitary Tumors. EMedicine. Available online at http://emedicine.medscape.com/article/1157189-overview. Accessed on October 12, 2012.

Pituitary Disorders. Pituitary Network Association. Available online at https://www.pituitary.org/library/disorders.aspx?page_id=1043. Accessed on October 12, 2012.

(Updated September 27, 2012) Empty Sella Syndrome. MedlinePlus. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000349.htm. Accessed on October 24, 2012.

UCLA Neurosurgery. Available online at http://neurosurgery.ucla.edu/body.cfm?id=185. Accessed on October 24, 2012.

(Reviewed May 8, 2012). Hypogonadotropic hypogonadism. Pubmed Health. Available online at http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001427/. Accessed on October 24, 2012.

Read more from the original source:
Pituitary Disorders - labtestsonline.org

Recommendation and review posted by sam

Mayo Clinic's approachTeamwork

The Transgender and Intersex Specialty Care Clinic (TISCC) provides integrated medical, psychosocial and surgical intervention to individuals with gender dysphoria or incongruence and to those with disorders of sexual development. The team includes providers from various specialties including endocrinology, pediatric endocrinology, social work, psychiatry, psychology, voice therapy, gynecology and plastic surgery.

Treatments offered include:

Before you start treatment, you will meet with at least one member of the TISCC medical team a doctor or nurse practitioner and a member of the TISCC mental health team, such as a social worker, psychologist or psychiatrist. You'll have a complete medical evaluation to make sure that your treatment risks are identified and addressed. Evaluation of your mental health ensures that any mood or mental health concerns are reasonably well-managed before you start the hormone therapy.

Each person is different. Your providers will look at your specific case in order to come up with the best recommendations for you. Your health care team will work with you during your treatment and make sure your expectations are realistic. Your team wants to make sure your goals are being met, any risks are managed and your questions are answered.

Mayo Clinic specialists are committed to providing the latest, most comprehensive treatment options for gender dysphoria. Your Mayo Clinic specialist's advice about the best treatment for you will be based on expert knowledge of and experience with all treatment options for gender dysphoria.

At Mayo Clinic, endocrinologists, psychiatrists, psychologists, nurse practitioners, social workers and surgeons work together to provide exactly the care you need.

Having all of this expertise in a single place, focused on you, means that you're not just getting one opinion your care is discussed among the team, your test results are available quickly, your appointments are scheduled in coordination and highly specialized experts are all working together to determine what's best for you.

Mayo Clinic has major campuses in Phoenix and Scottsdale, Arizona; Jacksonville, Florida; and Rochester, Minnesota. The Mayo Clinic Health System has dozens of locations in several states.

For more information on visiting Mayo Clinic, choose your location below:

Mayo Clinic works with hundreds of insurance companies and is an in-network provider for millions of people.

In most cases, Mayo Clinic doesn't require a physician referral. Some insurers require referrals, or may have additional requirements for certain medical care. All appointments are prioritized on the basis of medical need.

Learn more about appointments at Mayo Clinic.

Please contact your insurance company to verify medical coverage and to obtain any needed authorization prior to your visit. Often, your insurer's customer service number is printed on the back of your insurance card.

Aug. 31, 2017

See the rest here:
Masculinizing hormone therapy - Care at Mayo Clinic - Mayo ...

Recommendation and review posted by Bethany Smith

Mesenchymal stem cells (MSCs) are found in the bone marrow and are responsible for bone and cartilage repair. On top of that, they can also produce fat cells. Early research suggesting that MSCs could differentiate into many other cell types and that they could also be obtained from a wide variety of tissues other than bone marrow have not been confirmed. There is still considerable scientific debate surrounding the exact nature of the cells (which are also termed Mesenchymal stem cells) obtained from these other tissues.

As of now, no treatments using mesenchymal stem cells are proven to be effective. There are, however, some clinical trials investigating the safety and effectiveness of MSC treatments for repairing bone or cartilage. Other trials are investigating whether MSCs might help repair blood vessel damage linked to heart attacks or diseases such as critical limb ischaemia, but it is not yet clear whether these treatments will be effective.

Several other features of MSCs, such as their potential effect on immune responses in the body to reduce inflammation to help treat transplant rejection or autoimmune diseases are still under thorough investigation. It will take numerous studies to evaluate their therapeutic value in the future.

Originally posted here:
Stem Cell Therapy & Treatment - Diseases and Conditions

Recommendation and review posted by Bethany Smith

What is hypogonadism?

Hypogonadism is a condition in which the testicles are not working the way they should.

In an adult, the testicles have two main functions: to make testosterone (the male hormone) and sperm. These activities are controlled by a part of the brain called the pituitary. The pituitary sends signals (called gonadotropins) to the testicles that, under normal conditions, cause the testicles to produce sperm and testosterone.

The pituitary signals can change based on the feedback signals that the brain receives from the testicle. Hypogonadism can therefore be divided into two main categories:

These categories are important because they may influence the way that hypogonadism is treated, and play a role in the results.

Testicular failure occurs when the brain is signaling the testicle to make testosterone and sperm, but the testicles are not responding correctly. As a result, the brain increases the amount of the gonadotropins signals, which causes a higher-than-normal level of these signals in the blood. For this reason, this condition is also referred to as hypergonadotropic hypogonadism. This is the most common category of hypogonadism.

Secondary hypogonadism (also called hypogonadotropic hypogonadism) occurs when the brain fails to signal the testicles properly. In men who have secondary hypogonadism, the testosterone levels may be very low, and sperm are usually missing from the semen. Some boys are born with this condition. In most cases, it is discovered when a boy fails to go through puberty.

Causes of primary hypogonadism include:

Causes of secondary hypogonadism include:

Low testosterone: Hypogonadism may be diagnosed when a man has symptoms of low testosterone, including low energy, fatigue, and a lower sexual drive.

Patients with secondary hypogonadism are usually diagnosed during their teen years because they have not started puberty. These patients may not develop the body type, muscle build, or hair pattern seen in adult males. Some men will also have a poor sense of smell.

Infertility: Hypogonadism may be diagnosed when a man has a problem with fertility (cannot father a child) and is found to have no sperm or only a very low number of sperm in the semen.

Continued here:
Hypogonadism | Cleveland Clinic

Recommendation and review posted by Bethany Smith

Most men who require hormone replacement therapy with testosterone have some form of testicular injury or primary hypogonadism. In other words, the problem is all in their balls. Those of us who have secondary hypogonadism often have perfectly functioning testes, but the problem lies elsewhere in whats known as the Hypothalamus Pituitary Testicular Axis (HPTA), which is responsible for keeping our male hormones in proper balance.

The problem with secondary hypogonadism, is that the treatment actually CAUSES primary hypogonadism by introducing exogenous (external) testosterone into the system. To understand that, first lets go over some basics

Hypothalamus:Among other things, this part of your brain sends GnRH (gonadotropin releasing hormone) down to instruct the pituitary gland to create more LH and FSH.

Pituitary Gland:Among other things (like growth hormone), this gland at the base of your brain secretes LH (luteinizing hormone) and FSH (follicle stimulating hormone), which travel down to the testes / gonads to instruct them to create more testosterone.

Testes / Gonads:Endocrinologists might get upset that I use these terms interchangeably. Oh well, screw em. You get the point. Your balls get the message from your pituitary gland to make more testosterone.

The Axis:The important thing to remember about the hypothalamus pituitary testicular axis (HPTA), also sometimes called thehypothalamic-pituitary-gonadal axis (HPG), is that it does not run only in one direction. The body tries to reach homeostasis a healthy balance of these hormones and the entire system can fall out of whack once you start introducing any of these hormones from outside sources. Which brings me to

The Problem With Taking Testosterone to Treat Secondary Hypogonadism:First of all, lets be clear I take testosterone to treat my secondary hypogonadism. Thats because there is currently no choice. Why cure something when you can have a customer for life? Why treat my bodys inability to create enough GnRH when that would require research money and you already have a product that fixes my symptoms ?

Digression aside, the problem with introducing an external source of testosterone is that eventually your gonads see that they are no longer needed. They pack their bags, or rather pack INTO their bags, and practically disappear over time. Now guess what? Not only do I have secondary hypogonadism, which might have been made even worse, but I now have a classic case of primary hypogonadism to deal with if I the medical community should ever find a treatment for secondary hypogonadism.

Heres an idea Why dont pharmaceutical companies make GnRH and market that to the endocrinologists so they can treat the source of my problem? Am I being naive here? Is there more to it than my not-medically-trained mind understands?

All gripes aside, I do feel great. Sure Ill be tied to this drug like a prisoner for the rest of my life, but I feel ten years younger. Im happy, confident, strong, lean, sharp, motivated, and a lot more fun in the bedroom. And Ive yet to see any CONVINCING studies about the long-term health dangers of testosterone replacement in hypogonadal men. Heart disease? Prostate cancer? Show me the studies? These are often-quoted side-effects, but all I hear are doctors deducing them because, for instance, taking away a mans testosterone seems to help with pre-existing conditions of prostate cancer. But that is not a cause-and-effect relationship. Just because removing testosterone helps treat or minimizes the recurrence of prostate cancer, doesnt mean it causes prostate cancer. Does it? OK, ok, thats anothe post entirely

See original here:
Primary Hypogonadism VS Secondary Hypogonadism ...

Recommendation and review posted by sam

Ever since 2012, when researchers first discovered that bacterial immune systems could be hijacked to edit DNA in living creatures, CRISPR has been hailed as a maker of revolutions. This was the year that prediction felt like it was starting to come true. U.S. scientists used the CRISPR gene editing technique to treat a common genetic heart disease in a human embryo. Many morediseases were successfully treated in mice using CRISPR. Hell, a particularly enthusiastic biohacker even spontaneously injected himself with muscle-growth genes while giving a talk at a conference.

But if 2017 was the year that the potential of CRISPR began to come into focus, 2018 may be the year that potential begins to be realized.

Next year, the first human trials of CRISPR-based treatments in the U.S. and Europe are slated to begin.

This month, biotech firm CRISPR Therapeutics became the first to submit a clinical trial application to European regulators. Tests are set to begin next year for its therapy that combines CRISPR gene editing and stem cell therapy to treat the blood disorder beta thalassemia. CEO Samarth Kulkarni told Gizmodo that the company also plans to file an application to conduct a clinical trial using a similar therapy to treat sickle cell disease in the first half of 2018. In 2018, the first human is going to get dosed with CRISPR in the clinic, Kulkarni told Gizmodo. And were going to be the first ones to do it.

Both disorders are genetic, caused by mutations to the genes that produce hemoglobin, a protein essential to ensuring that red blood cells ferry oxygen throughout the body. Without that oxygen, people can suffer from severe anemia, developmental delays, damage to organs, and pulmonary hypertension. The idea is extract stem cells from patients bone marrow and correct the faulty genes with CRISPR, a gene-editing technique that allows scientists to cut and paste tiny snippets of genetic code. Then those edited cells would be infused back into the body, where they would multiply, eventually outnumbering the diseased cells. Sickle cell disease and beta thalassemia are good candidates for CRISPR because in many cases, they are caused by a mutation to one single DNA letter.

At Stanford, a different spin on using CRISPR to treat sickle cell disease is also moving toward clinical trials. Matthew Porteus, who heads the research, said that his group expects to file a clinical trial application with the FDA by the end of 2018 and begin trials in 2019. Our New Years resolution for 2018 is to gather the data so we can file a [trial application] by the end of the year, so we can start a clinical trial in 2019, Porteus told Gizmodo. We just need to check off all the boxes.

Chinese scientists, meanwhile, used CRISPR for the first time on a human in 2016, and conducted a second human trial this year, setting off a biomedical duel between the U.S. and China and sparking concerns that the trials were irresponsibly premature. The first U.S. human CRISPR trial was slated to begin this summerat the University of Pennsylvania, after receiving a regulatory stamp of approval to proceed last year. It is unclear what has caused that trials delay.

Porteus said that he expects 2018 will bring many more preclinical studies demonstrating how CRISPR might be used to treat different diseases. In 2017, there were several such studies, addressing devastating diseases and conditions such as Huntingtons disease, Lou Gherigs disease, and an inherited form of hearing loss in mice.

There is going to be a lot of behind-the-scenes work of turning those into a real clinical protocol, Porteus said. He also predicted 2018 will see applications for more clinical trials, though most likely ones the involve simply deleting a problematic gene rather than correcting it.

George Church, the famed Harvard geneticist, told Gizmodo that he expects CRISPR will get much more precise in the coming year. He also expects an uptick in research on how to use CRISPR to solve problems that dont have other good solutions, like eliminating zoonotic diseases such as Lyme disease and malaria by using whats known as a gene drive to alter the DNA of wild species, or even growing transplantable organs in pigs.

The MIT synthetic biologist Kevin Esvelt said he expects there to be more gene therapy progress using a brand-new CRISPR technique that relies on base editing, or chemically altering a single letter of DNA rather than using CRISPR to actually cut through DNAs double helix to change it. The only prediction Im absolutely confident of making is that 2018 will see CRISPR continue to markedly accelerate research, both by simplifying previously difficult tasks and by making it possible to conduct experiments we could never previously contemplate, Esvelt said. Beyond that, theres no telling.

Hank Greely, a bioethicist at Stanford, told Gizmodo that he expects to see advancement with CRISPR outside of biomedicine. Among his predictions: Several groups will come up with completely new and unexpected uses for CRISPR, he said. And someone, somewhere will do a gene-drive trial in a controlled but non-laboratory environment.

Greely also predicts that CRISPR inventors will win a Nobel prize. (Though theres no telling which of CRISPRs inventorsits a bitterly disputed claim that award would go to.)

There are still significant hurdles, though, to reaching a future in which molecular cutting and pasting can act as a one-time cure-all for any genetic disease. For one, treating diseases that require editing DNA while its still inside the human body, such as amyotrophic lateral sclerosis,is a lot harder (and riskier) than removing cells, editing them in a lab, and putting them back into the body, as researchers will do in the trials slated to start in the next two years. But addressing many diseases will require whats known as in-vivo treatment. And scientists are still working to figure out the best way to deliver therapies inside the body effectively.

For ex-vivo treatments, the limit now is just whether we can do the work. I dont think there are obvious technical challenges. We just need to move into the clinic and test them out, Porteus said. For for in-vivo treatments, there is a lot of room for improvement.

Greely said that while some CRISPR clinical trials will start soon, they wont wrap up in 2018. Even when science is moving at a breakneck speed, like it is with CRISPR, it still tends to move more slowly than we wish it would.

And we may also realize that the high-tech solution is not always the best option.

Harvard geneticist Church said CRISPR may be due for a reality check. For example, he said, families may decide to undergo genetic counseling before having kids to assess their risk of passing on genetic diseases, rather than having children and treating them with CRISPR therapies likely to be $1 million per dose.

Whatever is in store for 2018, its important to remember that in the realm of science, progress is never a straight line.

More:
In 2018, We Will CRISPR Human Beings - gizmodo.com

Recommendation and review posted by sam

In fewer than five years, the gene-editing technology known as Crispr has revolutionized the face and pace of modern biology. Since its ability to find, remove, and replace genetic material was first reported in 2012, scientists have published more than 5,000 papers mentioning Crispr. Biomedical researchers are embracing it to create better models of disease. And countless companies have spun up to commercialize new drugs, therapies, foods, chemicals, and materials based on the technology.

Usually, when weve referred to Crispr, weve really meant Crispr/Cas9a riboprotein complex composed of a short strand of RNA and an efficient DNA-cutting enzyme. It did for biology and medicine what the Model T did for manufacturing and transportation; democratizing access to a revolutionary technology and disrupting the status quo in the process. Crispr has already been used to treat cancer in humans, and it could be in clinical trials to cure genetic diseases like sickle cell anemia and beta thalassemia as soon as next year.

But like the Model T, Crispr Classic is somewhat clunky, unreliable, and a bit dangerous. It cant bind to just any place in the genome. It sometimes cuts in the wrong places. And it has no off-switch. If the Model T was prone to overheating, Crispr Classic is prone to overeating.

Even with these limitations, Crispr Classic will continue to be a workhorse for science in 2018 and beyond. But this year, newer, flashier gene editing tools began rolling off the production line, promising to outshine their first-generation cousin. So if you were just getting your head around Crispr, buckle up. Because gene-editing 2.0 is here.

Crisprs targeted cutting action is its defining feature. But when Cas9 slices through the two strands of an organisms DNA, the gene-editor introduces an element of risk. Cells can make mistakes when they repair such a drastic genetic injury. Which is why scientists have been designing ways to achieve the same effects in safer ways.

One approach is to mutate the Cas9 enzyme so it can still bind to DNA, but its scissors dont work. Then other proteinslike ones that activate gene expressioncan be combined with the crippled Cas9, letting them toggle genes on and off (sometimes with light or chemical signals) without altering the DNA sequence. This kind of epigenetic editing could be used to tackle conditions that arise from a constellation of genetic factors, as opposed to the straightforward single mutation-based disorders most well-suited to Crispr Classic. (Earlier this month, researchers at the Salk Institute used one such system to treat several diseases in mice, including diabetes, acute kidney disease, and muscular dystrophy.)

Other scientists at Harvard and the Broad Institute have been working on an even more daring tweak to the Crispr system: editing individual base pairs, one at a time. To do so, they had to design a brand-new enzymeone not found in naturethat could chemically convert an A-T nucleotide pairing to a G-C one. Its a small change with potentially huge implications. David Liu, the Harvard chemist whose lab did the work, estimates that about half of the 32,000 known pathogenic point mutations in humans could be fixed by that single swap.

I dont want the public to come away with the erroneous idea that we can change any piece of DNA to any other piece of DNA in any human or any animal or even any cell in a dish, says Liu. But even being where we are now comes with a lot of responsibility. The big question is how much more capable will this age get? And how quickly will we be able to translate these technological advances into benefits for society?"

Crispr evolved in bacteria as a primitive defense mechanism. Its job? To find enemy viral DNA and cut it up until there was none left. Its all accelerator, no brake, and that can make it dangerous, especially for clinical applications. The longer Crispr stays in a cell, the more chances it has to find something that sort of looks like its target gene and make a cut.

To minimize these off-target effects, scientists have been developing a number of new tools to more tightly control Crispr activity.

So far, researchers have identified 21 unique families of naturally occurring anti-Crispr proteinssmall molecules that turn off the gene-editor. But they only know how a handful of them work. Some bind directly to Cas9, preventing it from attaching to DNA. Others turn on enzymes that outjostle Cas9 for space on the genome. Right now, researchers at UC Berkeley, UCSF, Harvard, the Broad, and the University of Toronto are hard at work figuring out how to turn these natural off-switches into programmable toggles.

Beyond medical applications, these will be crucial for the continued development of gene drivesa gene-editing technology that quickly spreads a desired modification through a population. Being able to nudge evolution one way or the other would be a powerful tool for combating everything from disease to climate change. Theyre being considered for wiping out malaria-causing mosquitoes, and eradicating harmful invasive species. But out in the wild, they have the potential to spread out of control, with perhaps dire consequences. Just this year Darpa poured $65 million toward finding safer gene drive designs, including anti-Crispr off-switches.

Despite decades of advances, theres still so much scientists dont understand about how bugs in your DNA can cause human disease. Even if they know what genes are coded into a cells marching orders, its a lot harder to know where those orders get delivered, and how they get translated (or mistranslated) along the way. Which is why groups at Harvard and the Broad led by Crispr co-discoverer Feng Zhang are working with a new class of Cas enzymes that target RNA instead of DNA.

Since those are the instructions that a cells machinery reads to build proteins, they carry more information about the genetic underpinnings of specific diseases. And because RNA comes and goes, making changes to it would be useful for treating short-term problems like acute inflammation or wounds. The system, which theyre calling Repair, for RNA Editing for Programmable A to I Replacement, so far only works for one nucleotide conversion. The next step is to figure out how to do the other 11 possible combinations.

And scientists are finding new Cas enzymes all the time. Teams at the Broad have also been working to characterize cpf1a version of Cas that leaves sticky ends instead of blunt ones when it cuts DNA. In February, a group from UC Berkeley discovered CasY and CasX, the most compact Crispr systems yet. And researchers expect to turn up many more in the coming months and years.

Only time will tell if Crispr-Cas9 was the best of these, or merely the first that captured the imagination of a generation of scientists. We dont know whats going to wind up working best for different applications, says Megan Hochstrasser, who did her PhD in Crispr co-discoverer Jennifer Doudnas lab and now works at the Innovative Genomics Institute. So for now I think it makes sense for everyone to be pushing on all these tools all at once.

It will take many more years of work for this generation of gene-editors to find their way out of the lab into human patients, rows of vegetables, and disease-carrying pests. That is, if gene-editing 3.0 doesnt make them all obsolete first.

See the rest here:
Crispr Isnt Enough Any More. Get Ready for Gene Editing 2.0

Recommendation and review posted by sam

For many people today, amyotrophic lateral sclerosis, aka ALS or Lou Gehrigs disease, is most commonly linked with both the fundraising Ice Bucket Challenge and one its most famous patients, the physicist Stephen Hawking. However, it could soon have a brand-new distinction the next disease to be treatable using CRISPR-Cas9 gene-editing technology.

In work carried out by researchers at University of California, Berkeley, scientists have been able to disable the defective genethat triggers ALS in mice. While they didnt get rid of the disease permanently, the treatment did extend the mices life span by 25 percent. The therapy delayed the onset of the muscle-wasting symptoms that characterize ALS, which ultimately become fatal when they spread to the muscles which control breathing.

Some diseases, like Lou Gehrigs disease, are caused by gene mutations that lead a protein in our cells to malfunction, David Schaffer, a professor of chemical and biomolecular engineering and director of the Berkeley Stem Cell Center, told Digital Trends. A very promising approach is to disable or delete that mutated gene. CRISPR/Cas9 is a highly promising technology to do so, but this capability needs to be delivered to the target cells. We put together CRISPR-Cas9 with a highly promising gene delivery, based on a virus, in order to disable the disease causing gene SOD1 in an animal model of ALS.

The mice in the study were genetically engineered to exhibit a mutated human gene that is responsible for around 20 percent of all inherited forms of ALS. The team then used a specially engineered virusthat deliversa gene encoding the Cas9 protein,which in turn disabled the mutant gene responsible for ALS. The treated mice lived one month longer than the typical four-month life span of mice with ALS. An average healthy mouse lives for around two years.

Hopefully, were this to be carried over to humans, those time spans would beextended.There are challenges that remain before extending into human studies, such as using an improved virus optimized for humans, but we think there is a clear path to doing so, Schaffer said.

A paper describing the work was recently published in the journal Science Advances.

Continued here:
With CRISPR, geneticists have a powerful new weapon in the ...

Recommendation and review posted by Bethany Smith

Overview

Genetic testing involves examining your DNA, the chemical database that carries instructions for your body's functions. Genetic testing can reveal changes (mutations) in your genes that may cause illness or disease.

Although genetic testing can provide important information for diagnosing, treating and preventing illness, there are limitations. For example, if you're a healthy person, a positive result from genetic testing doesn't always mean you will develop a disease. On the other hand, in some situations, a negative result doesn't guarantee that you won't have a certain disorder.

Talking to your doctor, a medical geneticist or a genetic counselor about what you will do with the results is an important step in the process of genetic testing.

When genetic testing doesn't lead to a diagnosis but a genetic cause is still suspected, some facilities offer genome sequencing a process for analyzing a sample of DNA taken from your blood.

Everyone has a unique genome, made up of the DNA in all of a person's genes. This complex testing can help identify genetic variants that may relate to your health. This testing is usually limited to just looking at the protein-encoding parts of DNA called the exome.

Genetic testing plays a vital role in determining the risk of developing certain diseases as well as screening and sometimes medical treatment. Different types of genetic testing are done for different reasons:

Generally genetic tests have little physical risk. Blood and cheek swab tests have almost no risk. However, prenatal testing such as amniocentesis or chorionic villus sampling has a small risk of pregnancy loss (miscarriage).

Genetic testing can have emotional, social and financial risks as well. Discuss all risks and benefits of genetic testing with your doctor, a medical geneticist or a genetic counselor before you have a genetic test.

Before you have genetic testing, gather as much information as you can about your family's medical history. Then, talk with your doctor or a genetic counselor about your personal and family medical history to better understand your risk. Ask questions and discuss any concerns about genetic testing at that meeting. Also, talk about your options, depending on the test results.

If you're being tested for a genetic disorder that runs in families, you may want to consider discussing your decision to have genetic testing with your family. Having these conversations before testing can give you a sense of how your family might respond to your test results and how it may affect them.

Not all health insurance policies pay for genetic testing. So, before you have a genetic test, check with your insurance provider to see what will be covered.

In the United States, the federal Genetic Information Nondiscrimination Act of 2008 (GINA) helps prevent health insurers or employers from discriminating against you based on test results. Under GINA, employment discrimination based on genetic risk also is illegal. However, this act does not cover life, long-term care or disability insurance. Most states offer additional protection.

Depending on the type of test, a sample of your blood, skin, amniotic fluid or other tissue will be collected and sent to a lab for analysis.

The amount of time it takes for you to receive your genetic test results depends on the type of test and your health care facility. Talk to your doctor, medical geneticist or genetic counselor before the test about when you can expect the results and have a discussion about them.

If the genetic test result is positive, that means the genetic change that was being tested for was detected. The steps you take after you receive a positive result will depend on the reason you had genetic testing.

If the purpose is to:

Talk to your doctor about what a positive result means for you. In some cases, you can make lifestyle changes that may reduce your risk of developing a disease, even if you have a gene that makes you more susceptible to a disorder. Results may also help you make choices related to treatment, family planning, careers and insurance coverage.

In addition, you may choose to participate in research or registries related to your genetic disorder or condition. These options may help you stay updated with new developments in prevention or treatment.

A negative result means a mutated gene was not detected by the test, which can be reassuring, but it's not a 100 percent guarantee that you don't have the disorder. The accuracy of genetic tests to detect mutated genes varies, depending on the condition being tested for and whether or not the gene mutation was previously identified in a family member.

Even if you don't have the mutated gene, that doesn't necessarily mean you'll never get the disease. For example, the majority of people who develop breast cancer don't have a breast cancer gene (BRCA1 or BRCA2). Also, genetic testing may not be able to detect all genetic defects.

In some cases, a genetic test may not provide helpful information about the gene in question. Everyone has variations in the way genes appear, and often these variations don't affect your health. But sometimes it can be difficult to distinguish between a disease-causing gene and a harmless gene variation. These changes are called variants of uncertain significance. In these situations, follow-up testing or periodic reviews of the gene over time may be necessary.

No matter what the results of your genetic testing, talk with your doctor, medical geneticist or genetic counselor about questions or concerns you may have. This will help you understand what the results mean for you and your family.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Aug. 09, 2017

Excerpt from:
Genetic testing - About - Mayo Clinic

Recommendation and review posted by Bethany Smith

Overview

Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease.

Genes contain your DNA the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease.

Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.

Researchers are still studying how and when to use gene therapy. Currently, in the United States, gene therapy is available only as part of a clinical trial.

Gene therapy is used to correct defective genes in order to cure a disease or help your body better fight disease.

Researchers are investigating several ways to do this, including:

Gene therapy has some potential risks. A gene can't easily be inserted directly into your cells. Rather, it usually has to be delivered using a carrier, called a vector.

The most common gene therapy vectors are viruses because they can recognize certain cells and carry genetic material into the cells' genes. Researchers remove the original disease-causing genes from the viruses, replacing them with the genes needed to stop disease.

This technique presents the following risks:

The gene therapy clinical trials underway in the U.S. are closely monitored by the Food and Drug Administration and the National Institutes of Health to ensure that patient safety issues are a top priority during research.

Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are research studies that help doctors determine whether a gene therapy approach is safe for people. They also help doctors understand the effects of gene therapy on the body.

Your specific procedure will depend on the disease you have and the type of gene therapy being used.

For example, in one type of gene therapy:

Viruses aren't the only vectors that can be used to carry altered genes into your body's cells. Other vectors being studied in clinical trials include:

The possibilities of gene therapy hold much promise. Clinical trials of gene therapy in people have shown some success in treating certain diseases, such as:

But several significant barriers stand in the way of gene therapy becoming a reliable form of treatment, including:

Gene therapy continues to be a very important and active area of research aimed at developing new, effective treatments for a variety of diseases.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Sept. 13, 2016

Original post:
Gene therapy - About - Mayo Clinic

Recommendation and review posted by simmons

There is a potent thread winding its way through generations of human culture. From Ancient Egyptian rituals to Kurzweils Singularity, many paths have sprung up leading to the same elusive destination: immortality.

Today, the concept is as popular as its ever been, and technological advances are giving people hope that immortality, or at very least radical life extension, may be within reach. Is modern technology advanced enough to give people a second chance through cryonics?

Todays infographic, courtesy of Futurism, tackles our growing fascination with putting death on ice.

Robert C. W. Ettingers seminal work, The Prospect Of Immortality, detailed many of the scientific, moral, and economic implications of cryogenically freezing humans for later reanimation. It was after that book was published in 1962 that the idea of freezing ones body after death began to take hold.

One of the most pressing questions is, even if were able to revive a person who has been cryogenically preserved, will the persons memories and personality remain intact? Ettinger posits that long-term memory is stored in the brain as a long-lasting structural modification. Basically, those memories will remain, even if the brains power is turned off.

Source

There are three main steps in the cryogenic process:

1) Immediately after a patient dies, the body is cooled with ice packs and transported to the freezing location.

2) Next, blood is drained from the patients body and replaced with a cryoprotectant (basically the same antifreeze solution used to transport organs destined for transplant).

3) Finally, once the body arrives at the cryonic preservation facility, the body is cooled to -196C (-320.8F) over the course of two weeks. Bodies are generally stored upside-down in a tank of liquid nitrogen.

At prices ranging from about $30,000 to $200,000, cryopreservation may sound like an option reserved for the wealthy, but many people fund the procedure by naming a cryonics company as the primary benefactor of their life insurance policy. Meanwhile, in the event of a death that doesnt allow for preservation of the body, the money goes to secondary beneficiaries.

Even if we do eventually find a way to reanimate frozen humans, another important consideration is how those people would take care of themselves financially. Thats where a cryonics or personal revival trust comes into play. A twist on a traditional dynastic trust, this arrangement ensures that there are funds to cover costs of the cryopreservation, as well as ensure the grantor would have assets when theyre unthawed. Of course, there are risks involved beyond the slim possibility of reanimation. The legal code in hundreds of years could be vastly different than today.

If you created a trust for specific purposes in 1711, it is unlikely it would function in the same way today.

Kris Knaplund, Law Professor, Pepperdine University

At last count, there are already 346 people in the deep freeze, with thousands more on the waiting list. As technology improves, those numbers are sure to continue rising.

Time will tell whether cryonically preserved people are able to cheat death. In the meantime? The cryonics industry is alive and well.

Interested in more infographics on future technology?Help us make the first Visual Capitalist book a reality on Kickstarter.

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Cryonics: Putting Death on Ice - Visual Capitalist

Recommendation and review posted by Bethany Smith

Overview

A bone marrow transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or diseased bone marrow. A bone marrow transplant is also called a stem cell transplant.

A bone marrow transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy blood cells.

Bone marrow transplants may use cells from your own body (autologous transplant) or from a donor (allogeneic transplant).

Mayo Clinic's approach

A bone marrow transplant may be used to:

Bone marrow transplants can benefit people with a variety of both cancerous (malignant) and noncancerous (benign) diseases, including:

Bone marrow is the spongy tissue inside some bones. Its job is to produce blood cells. If your bone marrow isn't functioning properly because of cancer or another disease, you may receive a stem cell transplant.

To prepare for a stem cell transplant, you receive chemotherapy to kill the diseased cells and malfunctioning bone marrow. Then, transplanted blood stem cells are put into your bloodstream. The transplanted stem cells find their way to your marrow, where ideally they begin producing new, healthy blood cells.

A bone marrow transplant poses many risks of complications, some potentially fatal.

The risk can depend on many factors, including the type of disease or condition, the type of transplant, and the age and health of the person receiving the transplant.

Although some people experience minimal problems with a bone marrow transplant, others may develop complications that may require treatment or hospitalization. Some complications could even be life-threatening.

Complications that can arise with a bone marrow transplant include:

Your doctor can explain your risk of complications from a bone marrow transplant. Together you can weigh the risks and benefits to decide whether a bone marrow transplant is right for you.

If you receive a transplant that uses stem cells from a donor (allogeneic transplant), you may be at risk of developing graft-versus-host disease (GVHD). This condition occurs when the donor stem cells that make up your new immune system see your body's tissues and organs as something foreign and attack them.

Many people who have an allogeneic transplant get GVHD at some point. The risk of GVHD is a bit greater if the stem cells come from an unrelated donor, but it can happen to anyone who gets a bone marrow transplant from a donor.

GVHD may happen at any time after your transplant. However, it's more common after your bone marrow has started to make healthy cells.

There are two kinds of GVHD: acute and chronic. Acute GVHD usually happens earlier, during the first months after your transplant. It typically affects your skin, digestive tract or liver. Chronic GVHD typically develops later and can affect many organs.

Chronic GVHD signs and symptoms include:

You'll undergo a series of tests and procedures to assess your general health and the status of your condition, and to ensure that you're physically prepared for the transplant. The evaluation may take several days or more.

In addition, a surgeon or radiologist will implant a long thin tube (intravenous catheter) into a large vein in your chest or neck. The catheter, often called a central line, usually remains in place for the duration of your treatment. Your transplant team will use the central line to infuse the transplanted stem cells and other medications and blood products into your body.

If a transplant using your own stem cells (autologous transplant) is planned, you'll undergo a procedure called apheresis (af-uh-REE-sis) to collect blood stem cells.

Before apheresis, you'll receive daily injections of growth factor to increase stem cell production and move stem cells into your circulating blood so that they can be collected.

During apheresis, blood is drawn from a vein and circulated through a machine. The machine separates your blood into different parts, including stem cells. These stem cells are collected and frozen for future use in the transplant. The remaining blood is returned to your body.

If a transplant using stem cells from a donor (allogeneic transplant) is planned, you will need a donor. When you have a donor, stem cells are gathered from that person for the transplant. This process is often called a stem cell harvest or bone marrow harvest. Stem cells can come from your donor's blood or bone marrow. Your transplant team decides which is better for you based on your situation.

Another type of allogeneic transplant uses stem cells from the blood of umbilical cords (cord blood transplant). Mothers can choose to donate umbilical cords after their babies' births. The blood from these cords is frozen and stored in a cord blood bank until needed for a bone marrow transplant.

After you complete your pretransplant tests and procedures, you begin a process known as conditioning. During conditioning, you'll undergo chemotherapy and possibly radiation to:

The type of conditioning process you receive depends on a number of factors, including your disease, overall health and the type of transplant planned. You may have both chemotherapy and radiation or just one of these treatments as part of your conditioning treatment.

Side effects of the conditioning process can include:

You may be able to take medications or other measures to reduce such side effects.

Based on your age and health history, your doctor may recommend lower doses or different types of chemotherapy or radiation for your conditioning treatment. This is called reduced-intensity conditioning.

Reduced-intensity conditioning kills some cancer cells and somewhat suppresses your immune system. Then, the donor's cells are infused into your body. Donor cells replace cells in your bone marrow over time. Immune factors in the donor cells may then fight your cancer cells.

Your bone marrow transplant occurs after you complete the conditioning process. On the day of your transplant, called day zero, stem cells are infused into your body through your central line.

The transplant infusion is painless. You are awake during the procedure.

The transplanted stem cells make their way to your bone marrow, where they begin creating new blood cells. It can take a few weeks for new blood cells to be produced and for your blood counts to begin recovering.

Bone marrow or blood stem cells that have been frozen and thawed contain a preservative that protects the cells. Just before the transplant, you may receive medications to reduce the side effects the preservative may cause. You'll also likely be given IV fluids (hydration) before and after your transplant to help rid your body of the preservative.

Side effects of the preservative may include:

Not everyone experiences side effects from the preservative, and for some people those side effects are minimal.

When the new stem cells enter your body, they begin to travel through your body and to your bone marrow. In time, they multiply and begin to make new, healthy blood cells. This is called engraftment. It usually takes several weeks before the number of blood cells in your body starts to return to normal. In some people, it may take longer.

In the days and weeks after your bone marrow transplant, you'll have blood tests and other tests to monitor your condition. You may need medicine to manage complications, such as nausea and diarrhea.

After your bone marrow transplant, you'll remain under close medical care. If you're experiencing infections or other complications, you may need to stay in the hospital for several days or sometimes longer. Depending on the type of transplant and the risk of complications, you'll need to remain near the hospital for several weeks to months to allow close monitoring.

You may also need periodic transfusions of red blood cells and platelets until your bone marrow begins producing enough of those cells on its own.

You may be at greater risk of infections or other complications for months to years after your transplant.

A bone marrow transplant can cure some diseases and put others into remission. Goals of a bone marrow transplant depend on your individual situation, but usually include controlling or curing your disease, extending your life, and improving your quality of life.

Some people complete bone marrow transplantation with few side effects and complications. Others experience numerous challenging problems, both short and long term. The severity of side effects and the success of the transplant vary from person to person and sometimes can be difficult to predict before the transplant.

It can be discouraging if significant challenges arise during the transplant process. However, it is sometimes helpful to remember that there are many survivors who also experienced some very difficult days during the transplant process but ultimately had successful transplants and have returned to normal activities with a good quality of life.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Living with a bone marrow transplant or waiting for a bone marrow transplant can be difficult, and it's normal to have fears and concerns.

Having support from your friends and family can be helpful. Also, you and your family may benefit from joining a support group of people who understand what you're going through and who can provide support. Support groups offer a place for you and your family to share fears, concerns, difficulties and successes with people who have had similar experiences. You may meet people who have already had a transplant or who are waiting for a transplant.

To learn about transplant support groups in your community, ask your transplant team or social worker for information. Also, several support groups are offered at Mayo Clinic in Arizona, Florida and Minnesota.

Mayo Clinic researchers study medications and treatments for people who have had bone marrow transplants, including new medications to help you stay healthy after your bone marrow transplant.

If your bone marrow transplant is using stem cells from a donor (allogeneic transplant), you may be at risk of graft-versus-host disease. This condition occurs when a donor's transplanted stem cells attack the recipient's body. Doctors may prescribe medications to help prevent graft-versus-host disease and reduce your immune system's reaction (immunosuppressive medications).

After your transplant, it will take time for your immune system to recover. You may be given antibiotics to prevent infections. You may also be prescribed antifungal, antibacterial or antiviral medications. Doctors continue to study and develop several new medications, including new antifungal medications, antibacterial medications, antiviral medications and immunosuppressive medications.

After your bone marrow transplant, you may need to adjust your diet to stay healthy and to prevent excessive weight gain. Maintaining a healthy weight can help prevent high blood pressure, high cholesterol and other negative health effects.

Your nutrition specialist (dietitian) and other members of your transplant team will work with you to create a healthy-eating plan that meets your needs and complements your lifestyle. Your dietitian may also give you food suggestions to control side effects of chemotherapy and radiation, such as nausea.

Your dietitian will also provide you with healthy food options and ideas to use in your eating plan. Your dietitian's recommendations may include:

After your bone marrow transplant, you may make exercise and physical activity a regular part of your life to continue to improve your health and fitness. Exercising regularly helps you control your weight, strengthen your bones, increase your endurance, strengthen your muscles and keep your heart healthy.

Your treatment team may work with you to set up a routine exercise program to meet your needs. You may perform exercises daily, such as walking and other activities. As you recover, you can slowly increase your physical activity.

Oct. 13, 2016

Read the original:
Bone marrow transplant - About - Mayo Clinic

Recommendation and review posted by Bethany Smith

Transgender MedicalTrans Health: http://www.trans-health.comInformation on health clinics, resources, and organizations.

Transgender Care: http://www.transgendercare.comOlder website, but it has some good information on medical and surgical practices.

Hudsons FTM Resource Guide: http://www.ftmguide.org/Terrific resource for all things FTM. Presenting, clothing, grooming, hormones, and surgery are all covered on this site.

TRANSGENDER Therapists, and Medical Doctors, and Psychiatrists

THERAPISTS:

New Jersey:

Donna German Klein, MSW, LCSW268 Green Village RoadGreen Village, New Jersey 07935(973) 816-2920

Cameron MazzeoLGBT SpecialistMarkell Counseling74 Route 9 North, Suite 7Marlboro, NJ 07726phone: (732) 817-0103fax: (732) 817-0105

Karla Morse, MA, LPC, ACSMindful Therapy Center105 Evesboro-medford RdSuite MMarlton, New Jersey 08053(856) 302-0542 x7011I have worked with transgendered individuals as a specialty since 2004 and multicultural couples, families and groups since 1998.

Dr. Donna LobiondoPsychoforensics, LLC39 South Fullerton AvenueMontclair, New Jersey 07042(973) 968-5257

Jennifer Whitlock, LPC93 Main Street, Ground Floor (Also called Route 206)Newton, NJ. 07860Phone : (973) 222-3750Fax : (718) 992-9770Email : Jen@JenWhitlock.comWebsite : http://www.jenwhitlock.com/"I welcome the Gay, Lesbian, Bisexual, Transgender and Questioning population. Homosexuality is not a problem that must be cured, but there are challenges unique to people with alternate lifestyles. I can help people come out to loved ones, deal with harassment or merely discuss relationships without having to change the pronoun. I have advocated for transgender clients who have chosen to make transitions, and those who have decided to not make full transitions. I have run a support group for Male to Female (MtF) individuals, using psychodramatic action methods."

Margie NicholsInstitute for Personal Growth281 Pavonia AvenueJersey City, NJ. 07302Phone : (800) 379-9220Fax : (732) 246-8081Email : shrnklady@aol.comWebsite : http://www.ipgcounseling.com

Lisa O'Connor, MDHealthy Transitions LLC1390 Valley Road, Suite 1BStirling, NJ. 07980Phone : (908) 647-1688Fax : (908) 647-5180Ofice Managers Email : Carly@HealthyTransitions.mdWebsite : http://www.healthytransitions.mdMedical management: Hormone Replacement Therapy (HRT), Appropriate medication for mental health issues. Pre- and Post-Operative (GRS) care for TG clients. Pre-op Evaluation/letters: First and Second letters. Providing health care and mental health providers across the country with assistance on the appropriate care of all clientele under the gender umbrella. This includes assessment/diagnosis, appropriate hormone therapy, labs, as well as psychotherapy for the pre and post-operative transsexual. Dr. O'Connor is a voting member of The World Professional Association for Transgender Health (WPATH). Member of the American Medical Association (AMA). Member of the World Association for Sexual Health. On the Board of Directors of the Alliance for Gender Awareness (AGA). A Diplomat with the American Academy of Family Physicians (AAFP).

Dr Nina Williams, Licensed Psychologist5 Rosewood CourtSomerset, NJ. 08873Phone : (732) 800-4796Email : psych82654@aol.com

Dr. Andjelka (Angie) Stones, Ph.D., MAPA, MAPS860 Lower Ferry Road, Suite 1Ewing, NJ. 08268Phone : (609) 403-8740 x113Email : dr.stones@globalnewworld.comWebsite : http://www.globalnewworld.com"I specialize in Gay Parenting advice, pre and post becoming parents as well as Transgender pre and post op guidance. I have offered my services in Spain, UK and Sweden and currently teach Gender Psychology (among other subjects) on Graduate level. My services are flexible in respect of mode of contact as I work face to face, on Skype and via email."

Catherine B. Wetzell, MA, LPC, NCCEmail : catherine@healingrecoveryarts.comRadha N. Smith, MSW, LSWEmail : radha@healingrecoveryarts.com503 Washington Ave, Suite 2BNewtown, PA. 18940Phone : (215) 932-9904andMontgomery Knoll148 Tamarack CirclePrinceton, NJ. 08558http://www.healingrecoveryarts.com/

Pennsylvania:

Catherine B. Wetzell, MA, LPC, NCCEmail : catherine@healingrecoveryarts.comRadha N. Smith, MSW, LSWEmail : radha@healingrecoveryarts.com503 Washington Ave, Suite 2BNewtown, PA. 18940Phone : (215) 932-9904andMontgomery Knoll148 Tamarack CirclePrinceton, NJ. 08558http://www.healingrecoveryarts.com/

New York:

Mr. Griffin Hansbury841 BroadwaySuite 302New York, New York 10003(646) 495-9842I work with all kinds of people dealing with all kinds of issues, including: depression and anxiety, creative blocks, relationship difficulties, sexual issues, gender identity issues, life transitions, family stress, and more. I am also experienced and expert in working with LGBTQ clients, their partners, and families.

Karen H Senecal37 Washington Square WestSuite 1BNew York, New York 10011(646) 762-6030I offer psychoanalytic psychotherapy to individuals and couples. I work well with a diverse spectrum of issues including: anxiety, depression, grief and loss, shame and guilt, body image and life transitions. I take pride in offering a non-judgmental, affirmative place to talk about gender identities and sexualities.

Jason Relph1133 Broadway @ 26th StSuite 1107New York, New York 10010(646) 318-0000Are you in emotional pain and feeling overwhelmed? Are you experiencing depression or anxiety? Do you find yourself upset and discouraged by your relationships? Gay, lesbian, bisexual, transgendered, straight, polyamorous and clients in open relationships are encouraged to contact me as I am a LGBT and poly affirming psychotherapist, who is open to working with individuals or couples from any background. I work with clients dealing with family problems, depression, anxiety, relationship issues, trauma, grief, abuse, sexual and gender identity, loneliness and loss, coming out, work related stress, sexuality, and life transitions.

Dr. Janet Finell41 5th AvenueNew York, New York 10003(646) 351-1724As a psychologist and psychotherapist, I focus on gender and sexuality, work and intimacy issues. I interweave cognitive-behavioral-dynamic approaches and tailor them to the individual's needs. I use an interactive-here-and- now approach in assisting people toward developing their strengths and skills in the areas in which they're seeking help. General Concerns: Anxiety, Depression, Sexuality, Gender issues, Body-issues; self-esteem: coping skills. Client focus: Adults preferred: Individuals and couples.

Moonhawk River Stone, M.S., LMHC1448 Dalton DriveSchenectady, NY 12308Phone : (518) 506-1261Email : HawkRStone@aol.comWebsite : http://www.riverstoneconsult.comI am an internationally recognized expert in transgender care with 25 years experience working with transsexual, transgender and gender variant people of all ages, especially young gender variant children, and their families. When someone is contemplating a gender transition it is my approach to work with the whole family as everyone transitions in a gender transition. I have a solid record of success in workplace transitions for clients and have a consulting practice just for workplace transitions. My expertise lends itself to working with transgender clients from many varied racial, cultural, religious and ethnic backgrounds.

David R. Yonkin, LCSW211 W. 56th Street Suite 30-GNew York, NY. 10019Phone : 917-842-2655info@davidyonkin.comwww.davidyonkin.com

Shelley Juran, Ph.D.163 Clinton StreetBrooklyn Heights, NY. 11201Phone : (718) 625-6526Shelley Juran, Ph.D. is a licensed psychologist and certified (interpersonal) psychoanalyst who has worked with transgendered clients for over 20 years, since, as a faculty member at NYU Medical Center, she ran the daily operations of their gender clinic. Now she is a Full Professor of Psychology at Pratt Institute, where she teaches Sexuality and Gender courses, and sees, privately, in Brooklyn Heights, clients who are interested in making decisions about their life based upon an in-depth exploration of their issues.

Katherine Rachlin, Ph.D.49 West 24 ST.Ste. 901New York, NY 10010Phone : (212) 206-3636Email : KitRachlin@gmail.comWebsite : http://www.transgendertherapyny.com/Licensed Clinical Psychologist, Gender specialist, Certified Sex TherapistKatherine Rachlin, Ph.D. is a psychotherapist in private practice in New York City. She has special expertise in working with people who have concerns regarding gender identity and sexuality. Dr. Rachlin is an interactive, solution-focused therapist. Her therapeutic approach is to provide support and practical feedback to help clients effectively address personal life challenges. She integrates complementary methodologies and techniques to offer a highly personalized approach tailored to each client. With compassion and understanding, she works with each individual to help them build on their strengths and attain the personal growth they are committed to accomplishing.

SJ Langer, LCSW138 West 25th StreetNYC, NY. 10001Phone : (917) 617-0243Email : slangerlcsw@gmail.comWebsite : http://www.sjlanger.comWebsite : http://www.transgenderpsychotherapynyc.com"I provide individual and group psychotherapy. The following are some of my specialities. They include depression, anxiety, bipolar disorder, trauma, sexual abuse history, sexuality, transgender/transsexual/genderqueer identities, gender transition, queer sexuality, substance abuse/sobriety, immigration, HIV/AIDS, individuals in the performing and fine arts and healthcare professionals. Assessments and letters towards transition-related healthcare are also available. Please feel free to contact me to discuss arranging a consultation.

Aron Janssen, M.D.Assistant Professor of Child and Adolescent PsychiatryNYU Child Study CenterPhone : (212) 263-4344Email : aron.janssen@nyumc.orgWebsite : http://www.aboutourkids.orgWebsite : http://www.aboutourkids.org/families/care_at_the_csc/gender_sexuality_se...Aron Janssen, MD, is a clinical assistant professor of child and adolescent psychiatry at the NYU School of Medicine and clinical director of the Gender and Sexuality Service at the Child Study Center. Dr. Janssen's areas of expertise include LGBT mental health, gender identity and sexual orientation development, ADHD, anxiety and mood disorders, and psychopharmacology.

Mental Health Care Centers:

Brattleboro RetreatCentral Intake and Ambulatory ServicesAnna Marsh LaneP.O. Box 803Brattleboro, VT 05302Toll free: 1-800-RETREATAdmission Fax: 802-258-3791LGBT Inpatient Program In our LGBT-specific, LGBT-affirming mental health & addiction treatment program youll receive care from a team of professionals that understands how gender and sexual orientation issues can impact lives.http://www.brattlebororetreat.org

Callen Lorde356 W 18th StNew York, NY 10011Phone: (212) 271-7200Fax: (212) 271-7225Callen-Lorde Community Health Center provides sensitive, quality health care and related services targeted to New Yorks lesbian, gay, bisexual, and transgender communities in all their diversity regardless of ability to pay. To further this mission, Callen-Lorde promotes health education and wellness and advocates for gay, lesbian, bisexual, and transgender health issues.http://www.callen-lorde.org

Surgeons:

New York:

Nadeem A. Chaudhry, MDscarless.com121 Dekalb AveBrooklyn, NY 11201-5425Phone: 718 921-4181Specialties:revisionssilicone removaltrachea shave

Aaron Grotas, MDnewyorkuro.com10 Union Square EastSuite 3ANew York, NY 10003Phone: 212-844-8941Fax: 212-844-8901Specialties:Orchiectomy

Erik Goluboff, MDdrgoluboff.com10 Union Square EastSuite 3ANew York, NY 10003Phone: 212.844.8900Specialties:Orchiectomy

Jacob Heyman, MD109 E 38th StNew York, NY 10016Phone: (212) 684-4900Specialties:Orchiectomy

Elizabeth Kavaler, MDnyurological.com880 Fifth AvenueNew York NY 10021Phone: (212) 570-6800Fax. (212) 861-7964Specialties:post-surgical complications

Dorothy Min, MDdowntownwomenobgyn.comDowntown Women Ob-Gyn568 Broadway, Suite 304New York, NY 10012Phone: (212) 966-7600Specialties:Hysterectomy

Zoe Rodriguez, MDdrrodriguez.org10 Union Square EastSuite 2BNew York, NY 10003Phone: (212) 844-8590Specialty:Hysterectomy

Stacey Silvers, MDMadison ENT161 Madison AveSuite 11WNew York, NY 10016Phone: (212) 213-3339Specialty:Otolaryngologist

Stephen Teitelbaum, MD1st Ave at 16th St.New York, NY 10003Phone: (212) 844-8941Specialty:Orchiectomy

Prabhat Ahluwalia, MDCNY Advanced Gynecology140 Burwell St.Suite 1Little Falls, NYPhone: (315) 823-1111Specialty:FTM hysterectomy

Jeff Rockmore, MD1365 Washington Ave., Ste. 200Albany, NY 11206Phone: (518) 438-0505Specialty:MTF Top SurgeryFacial implants

Other states:

Kym Boyman, MDvtgyn.comVermont Gynecology23 Mansfield Ave.Burlington, VT 05401Phone: (802) 735-1252Specialty:HysterectomyPost-vaginoplasty gyn care

Beverly A. Fischer, MDbeverlyfischer.com12205-12207 Tullamore Rd.Timonium, MD 21093Phone: (410) 308-4700Fax: 410-308-4704Specialty:FTM Top Surgery

Joseph Rosen, MDDartmouth-Hitchcock Medical Center1 Medical Center DriveLebanon, NH 03766(603) 650-8456Specialty:MTF and FTM Top Surgery

Jeffrey Spiegel, MD, FACSdrspiegel.comAdvanced Facial Aesthetics830 Harrison Ave, Suite 1400Boston, MA 02118Phone: (617) 566-3223Specialty:Facial Feminization Surgery

See the rest here:
Medical & Mental Health Resources | LGBTQ

Recommendation and review posted by Bethany Smith

1. Rossouw JE, Anderson GL, Prentice RL, et al.; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321333....

2. Anderson GL, Limacher M, Assaf AR, et al.; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in post-menopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291(14):17011712.

3. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):13531368.

4. Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res. 2002;53(3):605619.

5. ACOG committee opinion no. 565. Hormone therapy and heart disease. Obstet Gynecol. 2013;121(6):14071410.

6. The American Academy of Family Physicians. Hormone replacement therapy. https://www.aafp.org/patient-care/clinical-recommendations/all/hrt.html. Accessed December 1, 2016.

7. Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition. Am J Public Health. 2006;96(7):12261235.

8. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012;19(3):257271.

9. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;(4):CD002978.

10. Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015;22(11):11551172.

11. Mohammed K, Abu Dabrh AM, Benkhadra K, et al. Oral vs transdermal estrogen therapy and vascular events: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(11):40124020.

12. ACOG practice bulletin no. 141. Management of menopausal symptoms. Obstet Gynecol. 2014;123(1):202216.

13. Jaakkola S, Lyytinen H, Pukkala E, Ylikorkala O. Endometrial cancer in postmenopausal women using estradiol-progestin therapy. Obstet Gynecol. 2009;114(6):11971204.

14. Goletiani NV, Keith DR, Gorsky SJ. Progesterone: review of safety for clinical studies. Exp Clin Psychopharmacol. 2007;15(5):427444.

15. Pickar JH, Yeh IT, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy. Fertil Steril. 2009;92(3):10181024.

16. Johnson K, Hauck F. Conjugated estrogens/bazedoxifene (Duavee) for menopausal symptoms. Am Fam Physician. 2016;93(4):307314.

17. Depypere H, Inki P. The levonorgestrel-releasing intrauterine system for endometrial protection during estrogen replacement therapy: a clinical review. Climacteric. 2015;18(4):470482.

18. Sideras K, Loprinzi CL. Nonhormonal management of hot flashes for women on risk reduction therapy. J Natl Compr Canc Netw. 2010;8(10):11711179.

19. Newton KM, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869879.

20. Lethaby A, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;(12):CD001395.

21. Cohen LS, Joffe H, Guthrie KA, et al. Efficacy of omega-3 for vasomotor symptoms treatment. Menopause. 2014;21(4):347354.

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25. Ockene JK, Barad DH, Cochrane BB, et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005;294(2):183193.

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27. Allen RH, Cwiak CA, Kaunitz AM. Contraception in women over 40 years of age. CMAJ. 2013;185(7):565573.

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29. Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society. Menopause. 2014;21(10):10631068.

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Continued here:
Hormone Therapy and Other Treatments for Symptoms of ...

Recommendation and review posted by Bethany Smith

Hypogonadism is a condition in which the bodys sex glands make little or no sex hormone. The sex glands are the testes in males and the ovaries in females. During puberty, sex hormones help control the development of breasts, testicles and pubic hair. They are also key for menstruation and sperm production.

Depending on when it begins, hypogonadism may affect the development of sex organs, interfere with puberty or cause infertility and sexual dysfunction.

Children with hypogonadism do not progress through puberty. Girls dont menstruate or develop breasts. Their overall growth is slowed.

Boys with hypogonadism have slowed muscle and genital development. Their arms and legs are long in relation to their torso. Body hair is sparse and their voice does not deepen.

Hypogonadism that appears after puberty will stop a womans menstrual cycle and may cause hot flashes. Men with hypogonadism have a decreased sex drive, muscle loss and breast development.

If the cause is a brain tumor, symptoms may include headaches or vision loss and a milky discharge from the breasts.

The two types of hypogonadism are called primary and central. In primary hypogonadism, the testes or ovaries dont function properly. In central hypogonadism, the hypothalamus and pituitary gland dont function properly. These areas of the brain signal the testes or ovaries to produce sex hormones. This form of hypogonadism can cause infertility.

The most common cause of primary hypogonadism is Klinefelter syndrome in boys and Turner syndrome in girls. One in 2,500 to 10,000 babies are born with Turner syndrome and 1 in 500 to 1,000 are born with Klinefelter syndrome.

Other causes of primary hypogonadism are:

Causes of central hypogonadism include:

Central hypogonadism affects boys and girls equally.

Diagnosis begins with a physical examination to check your childs progress through puberty. Your childs doctor will order blood tests to check the levels of testosterone or estrogen and the puberty hormones, such as LH (lutenizing hormone) and FSH (follicle-stimulating hormone).

Your childs doctor may also order imaging tests, such as an MRI or CT scan to check for tumors in the pituitary gland, and an ultrasound to look for ovarian cysts or other disorders of the ovaries.

Many forms of hypogonadism are treatable with hormone replacement therapy. Girls and women will take estrogen and progesterone are used for girls and women. Boys and men will take testosterone.

If hypogonadism is caused by a tumor on the pituitary gland, treatment may include radiation, medication or surgery to shrink or remove the tumor.

With ongoing hormone replacement therapy, men and women with hypogonadism are able to live a normal life.

The rest is here:
Hypogonadism | Children's Hospital of Philadelphia

Recommendation and review posted by simmons

[+]Enlarge

The CRISPR system uses a guide RNA (yellow) to direct the Cas9 enzyme (white) to a specific location in a cells DNA (blue) for cutting.

Credit: CRISPR Therapeutics

The gene editing technology CRISPR is one step closer to treating genetic diseases in humans. Last week, Crispr Therapeutics filed an application with European regulatory authorities to begin clinical trials for its CRISPR therapy CTX001 in a genetic blood condition called beta-thalassemia. The biotech firm expects to begin the trialthe first industry-sponsored study of a CRISPR drugnext year.

Samarth Kulkarni, CRISPR Therapeutics CEO

It is a momentous occasion for both our company and the field, says Samarth Kulkarni, CEO of Crispr Therapeutics. In early 2018, the firm will also ask the U.S. Food & Drug Administration for permission to use CTX001 to treat sickle cell disease. Vertex Pharmaceuticals today announced a 50-50 partnership with CRISPR Therapeutics to develop the drug in both beta-thalassemia and sickle cell.

Promising preclinical data presented at the American Society of Hematology (ASH) meeting in Atlanta this past weekend offered a glimpse of the strategies that Crispr Therapeutics and its many competitors are taking to treat the genetic blood diseases.

Since its conception in 2012, CRISPR has been swiftly adopted in research labs. By 2014, three biotech firms, each partly founded by one of the three inventors of CRISPR, had launched to transform the tool into a therapy. These three companies are now gearing up for their first-in-human studies, a breakneck pace for drug development.

CRISPR requires at least two basic components to edit genes: a guide RNA, which carries the code that specifies where to edit a genome, and an enzyme called Cas, which follows the guide RNA to make a cut in a cells DNA. Sometimes this cut is enough for a potential therapy. But to change the DNA or insert a new sequence, a third component, a template DNA, is required.

Both sickle cell disease and beta-thalassemia are caused by mutations in a gene that makes part of hemoglobin, the protein that carries oxygen throughout the blood. In sickle cell, the mutation causes normally donut-shaped red blood cells to warp into a crescent shape; the cells get stuck inside blood vessels, depriving tissues of oxygen. Beta-thalassemia is caused by mutations that prevent the production of fully functional hemoglobin, which for some people can cause severe anemia.

Instead of trying to fix the faulty DNA, Crispr Therapeutics and other companies are using the technology to reactivate a kind of hemoglobin found in infants. Everyone is born with high levels of a protein called fetal hemoglobin, which is mostly replaced with adult hemoglobin by three months of agethe same time that symptoms of sickle cell and beta-thalassemia appear. A gene called BCL11A represses the fetal hemoglobin production, but a rare genetic mutation in this gene is known to allow fetal hemoglobin production to continue.

Crispr Therapeutics lead drug candidate, CTX001, works by simply cutting BCL11A, basically removing the brakes on fetal hemoglobin production, Kulkarni says. On Sunday, the company presented results showing that its method edited over 90% of blood stem cells removed from patients with beta-thalassemia, dramatically increasing fetal hemoglobin in these cells.

Kulkarni says that extensive computer prediction, followed by cell and animal testing, has led them to a guide RNA in the CRISPR therapy that has no detectable off-target activitya potential side effect in which CRISPR accidently cuts the DNA in the wrong location. Stuart Orkin, a hematologist-oncologist at the Boston Childrens Hospital, says that off-target activity is one of the biggest safety concerns for gene editing in humans.

Crispr Therapeutics isnt the only company trying to increase fetal hemoglobin by targeting BCL11A. Intellia Therapeutics and Novartis have a partnership to do this with CRISPR. And Sangamo Therapeutics and Bioverativ are developing a similar therapy together using a different gene editing technology called zinc finger nucleases.

Meanwhile, Editas Medicine, another CRISPR company, presented an update at ASH on using its proprietary Cas enzyme, called Cpf1, to fix the mutation in the gene for adult hemoglobin. Charles Albright, chief scientific officer of Editas, says the company is simultaneously working on the fetal hemoglobin approach, but did not provide a timeline for when the sickle cell therapy would make it into clinical studies.

The hematology meeting also showcased many firms working on therapies for sickle cell and beta-thalassemia that dont require gene editing. Bluebird Bio, a gene therapy company, has ongoing clinical trials for both conditions using a virus to deliver a healthy copy of the hemoglobin gene into cells. Drug companies are also trying to treat sickle cell with small molecule drugs. Global Blood Therapeutics compound voxelotor, which increases hemoglobins ability to bind oxygen, is in Phase II and III clinical trials currently. And Epizyme is developing an inhibitor of an enzyme called histone methyltransferase, which could be another way to release the brakes on fetal hemoglobin production.

Everyone is working on these diseases because we know exactly what to do, and there are multiple different ways to get to the same end, a treatment, Orkin says. We dont know yet which program will be the bestBut the first one that is shown to be very effective and safe, could crowd out the others.

As it prepares to launch its first trial, Crispr Therapeutics has secured a contract manufacturer in Europe which will receive patient blood cells, edit them, and then ship them back to the clinical trial sites. Patients will then undergo chemotherapy or irradiation in preparation for their edited blood stem cells to be transplanted into the bone marrow, where they will hopefully produce healthier blood cells for life.

It is important that they do this very carefully, Orkin says. Because if there is a mistake or bad effect [from CRISPR], it will have repercussions beyond a single patient.

Read more here:
CRISPR gene editing is coming to the clinic | Chemical ...

Recommendation and review posted by simmons

Diagnosis

Your doctor will conduct a physical exam during which he or she will note whether your sexual development, such as your pubic hair, muscle mass and size of your testes, is consistent with your age. Your doctor may test your blood level of testosterone if you have any of the signs or symptoms of hypogonadism.

Early detection in boys can help prevent problems from delayed puberty. Early diagnosis and treatment in men offer better protection against osteoporosis and other related conditions.

Doctors base a diagnosis of hypogonadism on symptoms and results of blood tests that measure testosterone levels. Because testosterone levels vary and are generally highest in the morning, blood testing is usually done early in the day, before 10 a.m.

If tests confirm you have low testosterone, further testing can determine if a testicular disorder or a pituitary abnormality is the cause. Based on specific signs and symptoms, additional studies can pinpoint the cause. These studies may include:

Testosterone testing also plays an important role in managing hypogonadism. This helps your doctor determine the right dosage of medication, both initially and over time.

Treatment for male hypogonadism depends on the cause and whether you're concerned about fertility.

Hormone replacement. For hypogonadism caused by testicular failure, doctors use male hormone replacement therapy (testosterone replacement therapy, or TRT). TRT can restore muscle strength and prevent bone loss. In addition, men receiving TRT may experience an increase in energy, sex drive, erectile function and sense of well-being.

If a pituitary problem is the cause, pituitary hormones may stimulate sperm production and restore fertility. Testosterone replacement therapy can be used if fertility isn't an issue. A pituitary tumor may require surgical removal, medication, radiation or the replacement of other hormones.

In boys, testosterone replacement therapy (TRT) can stimulate puberty and the development of secondary sex characteristics, such as increased muscle mass, beard and pubic hair growth, and growth of the penis. Pituitary hormones may be used to stimulate testicle growth. An initial low dose of testosterone with gradual increases may help to avoid adverse effects and more closely mimic the slow increase in testosterone that occurs during puberty.

Several testosterone delivery methods exist. Choosing a specific therapy depends on your preference of a particular delivery system, the side effects and the cost. Methods include:

Injection. Testosterone injections (testosterone cypionate, testosterone enanthate) are safe and effective. Injections are given in a muscle. Your symptoms might fluctuate between doses depending on the frequency of injections.

You or a family member can learn to give TRT injections at home. If you're uncomfortable giving yourself injections, a nurse or doctor can give the injections.

Testosterone undecanoate (Aveed), an injection recently approved by the Food and Drug Administration, is injected less frequently but must be administered by a health care provider and can have serious side effects.

Gel. There are several gel preparations available with different ways of applying them. Depending on the brand, you either rub testosterone gel into your skin on your upper arm or shoulder (AndroGel, Testim, Vogelxo), apply with an applicator under each armpit (Axiron) or pump on your front and inner thigh (Fortesta).

As the gel dries, your body absorbs testosterone through your skin. Gel application of testosterone replacement therapy appears to cause fewer skin reactions than patches do. Don't shower or bathe for several hours after a gel application, to be sure it gets absorbed.

A potential side effect of the gel is the possibility of transferring the medication to another person. Avoid skin-to-skin contact until the gel is completely dry or cover the area after an application.

Oral testosterone isn't recommended for long-term hormone replacement because it might cause liver problems.

Testosterone therapy carries various risks, including contributing to sleep apnea, stimulating noncancerous growth of the prostate, enlarging breasts, limiting sperm production, stimulating growth of existing prostate cancer and blood clots forming in the veins. Recent research also suggests testosterone therapy might increase your risk of a heart attack.

Reduce stress. Talk with your doctor about how you can reduce the anxiety and stress that often accompany these conditions. Many men benefit from psychological or family counseling.

Support groups can help people with hypogonadism and related conditions cope with similar situations and challenges. Helping your family understand the diagnosis of hypogonadism also is important.

Although you're likely to start by seeing your family doctor or general practitioner, you may need to consult a doctor who specializes in the hormone-producing glands (endocrinologist). If your primary care doctor suspects you have male hypogonadism, he or she may refer you to an endocrinologist. Or, you can ask for a referral.

Here's some information to help you get ready for your appointment and know what to expect from your doctor.

Preparing a list of questions for your doctor will help you make the most of your time together. For male hypogonadism, some basic questions to ask your doctor include:

Don't hesitate to ask other questions you have.

Your doctor is likely to ask you a number of questions, such as:

Sept. 29, 2016

See more here:
Male hypogonadism - Diagnosis and treatment - Mayo Clinic

Recommendation and review posted by Bethany Smith

1987: CRISPR repeats were observed in bacterial genomes. The authors concluded, no sequence homologous to these has been found elsewhere in procaryotes, and the biological significance of these sequences is not known. Ishino et al. J. Bacteriology (1987) 169:5429-5433. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC213968/

2002: The term CRISPR was coined to describe the repetitive repeats observed in bacterial and archaeal genomes. Genes usually found associated with the CRISPR repeats were identified and named CRISPR Associated Proteins or Cas. Jansen et al. Mol. Microbiology. (2002) 43:1565-1575. http://www.ncbi.nlm.nih.gov/pubmed/11952905

2005: CRISPR spacer sequences were matched to foreign DNA. Bolotin et al. Microbiology (2005) 151:2551-2561. http://www.ncbi.nlm.nih.gov/pubmed/16079334

2006: CRISPR was first proposed to be a bacterial adaptive immune system. Makarova et al. Biol Direct (2006) 1:7. http://www.ncbi.nlm.nih.gov/pubmed/16545108.

2007: CRISPR loci were found to impart phage resistance in bacteria. It was determined that CRISPR sequences together with the Cas genes impart resistance and that resistance to specific phages was determined by the spacer sequences found between CRISPR repeats. Barrangou et al. Science. (2007) 315:1709-1712. http://www.ncbi.nlm.nih.gov/pubmed/17379808

2009: RNA guided RNA cleavage is first described. Hale et al. RNA (2008) 2:2572-2579. http://www.ncbi.nlm.nih.gov/pubmed/18971321

2010: The CRISPR/Cas system was identified as a bacterial and archeal immune system that targets and cleaves phage DNA. This system was found to be dependent on the bacteria containing CRISPR spacer sequences that match the phage DNA. Additionally researchers discovered that new spacer sequences could be inserted into the bacterial/archeal chromosome making the CRISPR/Cas system an adaptive immune system. Garneau et al. Nature. (2010) 468:67-71. http://www.ncbi.nlm.nih.gov/pubmed/21048762

2011: Cas9 from Streptococcus pyogenes was found to associate with two RNA molecules coined crRNA and tracrRNA and that all these components are required for protection against phage infection. Deltcheva et al. Nature (2011) 471:602-607. http://www.ncbi.nlm.nih.gov/pubmed/21455174

2012: Cas9 was found to be an endonuclease capable of introducing DSB in DNA and that this process is dependent on complementary binding of the crRNA to the target DNA. Two nuclease domains were found in Cas9 with the HNH domain cleaving the complementary strand and the RuvC-like domain cutting the non-complementary strand. Jinek et al. Science (2012) 337:816-821. http://www.ncbi.nlm.nih.gov/pubmed/22745249

2013: The CRISPR/Cas9 system was used to edit targeted genes in both human and mouse cells using designed crRNA sequences. Cong et al. Science (2013) 339:819-823. http://www.ncbi.nlm.nih.gov/pubmed/23287718

First use in plants. Li et al. Nat Biotechnol (2013) 8:688-691. http://www.ncbi.nlm.nih.gov/pubmed/23929339

Also first use in plants ? Nekrasov et al. Nat Biotechnol (2013) 8:691-693. http://www.ncbi.nlm.nih.gov/pubmed/23929340.

2014: The crystal structure of Cas9 complexed with both gRNA and targeted DNA was elucidated. Nishimasu et al. Cell (2014) 156:935-949. http://www.ncbi.nlm.nih.gov/pubmed/24529477

PAMs are identified as a key component of DNA target integration. Anders et al. Nature (2014) 513:569-573. http://www.ncbi.nlm.nih.gov/pubmed/25079318

sgRNA and Cas9 are directly delivered into cells without the use of a vector intermediate. Ramakrishna et al. Genome Res (2014) 24:1020-1027. http://www.ncbi.nlm.nih.gov/pubmed/24696462

2015: CRISPR/Cas9 was used to edit tri-chromosomal pre-implantation human embryos. Researchers attempted to repair the HBB locuswhich, when mutated, results in -thalassemia blood disorders. The researchers were unable to effectively repair the mutated locus and many off-target cleavages were observed. Liang et al. Protein and Cell (2015) 6:363-372. http://www.ncbi.nlm.nih.gov/pubmed/25894090

2015: An international moratorium is called for making heritable changes to the human genome using gene editing.At an international meeting convened by the National Academy of Science of the United States, the Institute of Medicine, The Chinese Academy of Sciences, and the Royal Society of London scientists called for a moratorium on making inheritable changes to the human genome. None of these groups have regulatory authority to prevent such research from taking place, however previous moratoriums where widely accepted in 1975 when an international group met in California to discuss gene editing in all species.http://www.nytimes.com/2015/12/04/science/crispr-cas9-human-genome-editing-moratorium.html?_r=0

2016: The USDA determines CRISPR/Cas9 edited crops will not be regulated as GMOs. Due to the lack of foreign DNA and the inability to distinguish CRISPR modified crops from those created by traditional plant breeding the USDA has determined that gene edited crops will not be regulated like traditional GMOs.http://www.nature.com/news/gene-edited-crispr-mushroom-escapes-us-regulation-1.19754

2016: The first human trial to use CRISPR gene editing gets approval from the NIH. A National Institute of Health advisory committee approved the use of CRISPR/Cas9 gene editing in a cancer therapy trial. The treatment will use CRISPR/Cas9 technology to edit the patients own T cells to target cancer.http://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137

Read the original here:
CRISPR Timeline CRISPR Update

Recommendation and review posted by Bethany Smith

$3,595,265 AWARDED

Rett Syndrome, as awful as the symptoms may be, provides us with several enormous advantages. First we know the cause: mutations in a single gene: MECP2. Second, Rett is not degenerative brain cells dont die. Third, work from RSRT trustee, Adrian Bird, suggests that the symptoms of Rett need not be permanent. These three facts make gene therapy an attractive therapeutic strategy.

In 2014 we launched a bold international collaboration of two gene therapy labs, Brian Kaspar and Steven Gray, and two MECP2 labs, Gail Mandel and Stuart Cobb. Together these labs brought together all the necessary skills and experience to determine if gene therapy is a viable therapeutic.

The Consortium worked through numerous challenges involving vector optimization (the Trojan horse that delivers the gene into a cell), gene construct optimization (what you package into the vector that regulates MeCP2 protein production), gene therapy dosage, and the best route to deliver it.

The data generated by the Consortium exceeded our expectations. They were able to develop a gene therapy product candidate with impressive efficacy, safety and delivery characteristics. Importantly, the magnitude of improvement in the mouse models of Rett is much greater than that of any drug tested and suggests that significant benefit may be achieved in people. We expect improvements, at least to some degree, regardless of age.

Based on the Consortium data the biotech company, AveXis, has now committed to advancing a gene therapy candidate into clinical trials. The company will announce before the end of 2017 what their timeline for trials will be.

Technological advances in gene therapy are happening quickly with more effective vectors being discovered that can carry larger DNA cargos and target a greater percentage of brain cells. While we anticipate encouraging results with our first clinical trial there will undoubtedly be room to improve. We have therefore recently awarded continued funding to the Gene Therapy Consortium to support second-generation gene therapy programs to leverage all technological advances.

Targeting the root problem in Rett, MECP2, can be done either at the DNA level (gene therapy or MECP2 Reactivation), the mRNA level or protein level.

Both the DNA and protein approaches carry a risk of potential dosage problems (too much MeCP2 may be harmful). An alternative approach is to use a technology called Spliceosome-Mediated RNA Trans-Splicing (SMaRT). This technology allows a mutation to be spliced out and repaired in RNA. The advantage is that this approach avoids any potential over-expression issues. Consortium member, Stuart Cobb, is working on this approach.

Gail Mandel of the Consortium is working on yet another approach, RNA editing. The possibility of correcting mutations in RNA has profound therapeutic potential, but had remained largely theoretical. Our focused investments have already demonstrated the potential for correcting MECP2 mutations in RNA in cells. We are currently increasing our investment to improve the editing efficiency and to identify optimal delivery methods.

See original here:
Gene Therapy Consortium - Rett Syndrome Research Trust

Recommendation and review posted by simmons

-A curious adult

June 25, 2014

That is a very interesting question! And one that many people wonder about. In fact, we answered a very similar question many years ago.

Twin genetics depend on what kind of twins we are talking about. Having identical twins is not genetic. On the other hand, fraternal twins can run in families.

Genetics can definitely play a role in having fraternal twins. For example, a woman that has a sibling that is a fraternal twin is 2.5 times more likely to have twins than average!

However, for a given pregnancy, only the mothers genetics matter. Fraternal twins happen when two eggs are simultaneously fertilized instead of just one. A fathers genes cant make a woman release two eggs.

It sounds like fraternal twins do indeed run in your family! But, since your son is the father, his genes are on the wrong side of the family tree. So, your family history likely didnt play a role in his wifes twin pregnancy.

The answer would be different if you were asking about a daughter. Also, although your sons family history of twins cant increase his wifes chance of having twins, he can pass those genes down to your granddaughter. With your strong family history of fraternal twins, this just might increase the chances of your granddaughter having twins!

But, your daughter-in-law is not necessarily having twins because of her genetics. Other things like environment, nutrition, age, and weight have also been linked to having twins as well. And there is always simple chanceevery woman has a chance at having fraternal twins. It is just that some women have a higher or lower chance.

Huh? Help Me Understand the Genetics!

Wait a minute. One type of twins has a genetic basis and the other does not? And, only the moms genetics matter? How is that possible?

Dont worry. It makes a lot of sense once we break down the biology.

The important difference between identical and fraternal twins is the number of fertilized eggs involved. Identical twins come from a single fertilized egg. Fraternal twins come from two different ones.

Identical twins happen when a single embryo splits in two soon after fertilization. This is why identical twins have identical DNA. They came from the same fertilized egg.

Since embryo splitting is a random event that happens by chance, it doesnt run in families. Genes are not involved. The same is not true for fraternal twins.

Fraternal twins happen when two independent eggs are each fertilized by different sperm. This is why the DNA of fraternal twins is different. In fact, fhe DNA of fraternal twins is no more similar than the DNA any other sibling pair.

Usually, a woman only releases a single egg at a time. Fraternal twins can only happen if a mother releases two eggs in one cycle. This is called hyperovulation.

Unlike embryo splitting, ovulation is a normal biological process that is controlled by our genes. And, different women can have different versions of these ovulation genes.

Some women have versions (called alleles) of these genes that make them more likely to hyperovulate. This means there is a higher chance that two eggs could get fertilized at once, leading to fraternal twins.

The gene versions that increase the chance of hyperovulation can be passed down from parent to child. This is why fraternal twins run in families.

However, only women ovulate. So, the mothers genes control this and the fathers dont.

This is why having a background of twins in the family matters only if it is on the mothers side. And why your sons family genetics did not play a role in his twins.

We went over a lot of this stuff in our previous answer, but your question got me thinking. Our last answer on twins was done so long ago. Has recent research discovered anything new on this fascinating topic? They have indeed at least if you are a sheep!

Counting Sheep can Teach us about Twins

Scientists often turn to animals when they want to study a biological process. Some of the newest information we have about twin genetics comes from studying sheep.

Sheep were chosen because, like people, they typically give birth to a single lamb. However, they can sometimes have twins and triplets.

Different breeds of sheep naturally have higher or lower twin rates. These different breeds have different versions (called alleles) of some of their genes. Specific alleles can make certain breeds more likely to have twins.

We can compare the genes between these different breeds to try to find the genes controlling twinning. And, this is just what scientists did.

A thorough search for genes controlling twining in sheep identified several interesting ones. The breeds with higher twin rates had different alleles of these genes!

Three key sheep genes identified were named BMP15, GDF9, and BMPR1B. The specific gene names are not really important. Just know that all of these genes are involved in controlling ovulation. Which makes sense!

Remember, hyperovulation increases the chance of having fraternal twins. The sheep breeds with higher than average twin rates had versions of the genes that increase ovulation.

Sheep are a great tool to help us study twin genetics. The tricky part is connecting these findings to people.

It is harder to study humans. Scientists have tried to find links between the genes identified in sheep and human twin genetics. So far theyve found that some match up and some dont. This, in and of itself, is interesting!

Another gene called follicle-stimulating hormone, or FSH for short, has also been linked to twins in humans. Like the other three genes identified, this FSH is also involved in promoting ovulation, and mothers of fraternal twins often have high levels of it.

It seems that twin genetics is more complicated in humans than in sheep. More genes are likely involved. But, each new bit of information about the genes involved adds another puzzle piece to the complete genetic picture.

Maybe someday we will know all the genes that cause fraternal twins in people. But for now, you can just tell your son that his genetics likely didnt cause his twins. Scientists are still trying to figure out which, if any, genes on his wifes side could possibly be the culprits!

By Dr. Anja Scholze, Stanford University

See the rest here:
Twin Genetics and Heredity - Understanding Genetics

Recommendation and review posted by sam

Interest in the field of genome editing continues to heat up, fueled by technological advances and the first approval of a gene therapy in the United States. The latest development in this exciting frontier of science involves small viruses called AAVs (short for adeno-associated viruses) that have the power to overwrite DNA in human cells.

AAV biology is one of the most febrile areas of basic research, and were planning to explore its therapeutic potential through a new collaboration, says Craig Mickanin, who focuses on new tools and technologies as a director at the Novartis Institutes for BioMedical Research (NIBR).

Novartis will work with Homology Medicines, a biotech company with a proprietary AAV platform, to adapt and refine the technology for the treatment of a blood disorder and certain eye diseases. Novartis biologists with expertise in these conditions will work side-by-side with Homology scientists over the course of the collaboration announced November 13 to move projects toward clinical testing.

The collaboration is designed to accelerate an initiative at NIBR that engages researchers across the company who are involved in projects with a common denominator: the genetic reprogramming of cells. Homologys AAV technology may aid their work.

It is our hope that this collaboration will help advance our Cell and Gene Therapy initiative, says Susan Stevenson, an executive director at NIBR who leads the initiative.

AAV biology is one of the most febrile areas of basic research, and were planning to explore its therapeutic potential through a new collaboration.

Craig Mickanin, a director at NIBR who focuses on new tools and technologies

AAVs are unusual in one key respect. In contrast to larger viruses, they dont seem to cause illness. This built-in safety feature makes AAVs attractive tools for genome editing.

The benign viruses can be engineered to carry a specific genetic sequence, and they can be programmed to home in on a target site in the genome. When they arrive, AAVs trigger a process called homologous recombination, which overwrites a particular portion of a gene or even replaces an entire gene. In this way, AAVs can be used to correct genetic defects.

Homologous recombination may give AAVs an edge over other genome editing tools such as CRISPR in certain contexts.

Unlike AAVs, CRISPR employs molecular scissors to generate double-stranded breaks in DNA. The breaks can be repaired one of two ways. The repair mechanism that tends to dominate called non-homologous end joining results in the insertion or deletion of short DNA sequences, which typically break the original gene. As a result, its relatively easy for researchers to disrupt a gene with CRISPR, but its harder for them to fix an error in a gene.

We aim to select the right tool for the right project, says Mickanin, the technology specialist. In some cases, that will mean using AAVs to correct a genetic defect rather than disabling a gene.

The collaboration with Homology includes three work streams. The first focuses on a blood disorder. The Novartis-Homology team hopes to design a single AAV reagent that can be injected directly into the bloodstream of any patient with a defective gene to cure the disease. We want to figure out if these AAVs are safe enough to inject directly into the bloodstream and if we can use them to fix a defective gene once and for all, says Stevenson, the cell and gene therapy expert.

The second work stream involves diseases of the eye, a testing ground for gene editing therapies because such therapies can be delivered locally. Gene editing agents can be injected directly under the retina, for example, where researchers hope they will work without affecting the rest of the body. The fact that we can directly observe the treatment and its effects in the eye gives us an important opportunity for assessing gene editing efficacy and helping patients with eye disease, explains Cynthia Grosskreutz, Global Head of Ophthalmology at NIBR.

The final work stream is exploratory. Researchers from across NIBR will be able to nominate projects that could benefit from Homologys AAV technology. Homologys viruses will be tested on a variety of cell types and model systems, potentially exposing new opportunities for therapeutic applications.

This technology could be applied to many different diseases, Mickanin says. Were excited to work with the Homology team to explore the possibilities.

In addition to collaborating with Homology Medicines, Novartis has made an equity investment in the company.

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Small viruses could accelerate cell and gene therapy research

Recommendation and review posted by simmons