Anyone have objective data on the effectiveness of the …

@StemCellPioneers I think you raise an interesting argument, but not for the reasons you list. The FDA is at least trying to base decisions on ACTUAL DATA, whereas there IS NO VERIFIABLE DATA on the therapeutic use of stem cells. What the FDA is saying is that the study is limited, and thus should be interpreted with caution. Therefore, they are being CONSISTENT. Flawed or limited data does not equal legitimate data on which to base decisions. So yes, if a study is limited, according to the FDA, then it is acceptable that a potentially dangerous drug should be continued to be given to children.

I dont have access to this particular study from home, but I can already tell you that retrospective case control studies can have significant problems with bias and confounding. See, this study states in the methods The primary exposure measure was the presence of amphetamine, dextroamphetamine, methamphetamine, or methylphenidate according to informant reports or as noted in medical examiner records, toxicology results, or death certificates. Now, even without reading the paper, which I will, I can already identify a potential source of bias. Kids who experienced sudden death were probably a lot more likely to have an autopsy, where drugs would be found by toxicology, whereas the kids who died in auto accidents probably were less likely to have autopsies, and the investigators likely relied on interviews with the family (less reliable). Thus, I predict that when I read the study tomorrow, I will find more autopsies in the sudden death group, and thus a greater association of sudden death with stimulants (because they were found more frequently by a better method). We shall see.

In any event, at least the FDA is weighing DATA, pros and cons, etc. There have been many cases of the FDA pulling medications and-or issuing black box warnings (for example, the diet drug fen-phen). This is how the system works. No drug is perfect, and as such needs to be approved through prospective studies, and constantly reviewed via aftermarket analysis. If more proof accumulates indicating that stimulants are harmful in ADHD, you can be sure the FDA will pull the drugs from the market. In contrast, the stem cell pioneers are just pushing forward, without so much as a hint that there could be some benefit (save lots and lots of anecdotal stories, which could easily be attributed to placebo affects).

I will say this again (perhaps for the 5th or 6th time). As a physician-scientist I truly believe in the promise of stem cells. I really, really do. However, no one will ever know if stem cell treatments are effective if they arent studied in rigorous, well-controlled clinical trials. This is true of all new treatments. And I would ask, why are the purveyors of this treatment not the leaders in the field of stem cell research? You talk about reputable stem cell clinic or doctor, but I consider that a misnomer. No reputable doctor would perform these infusions without it being part of a clinical trial or as an already verified procedure. Furthermore, this thread has piqued my interest in this area, and Ive been doing a lot of web research over the past few days. Interestingly, quite a few of the doctors and clinics discussed on your very site have had major legal and ethical issues (including doctors that are heavily promoted), which argues against them being reputable. The doctors who run these clinics may claim to be scientists, but in reality, the bulk of cutting edge stem cell work is going on in major academic hospitals, not small, private clinics run by doctors with little to no scientific training.

Finally, I really hope you find what you are looking for in stem cell infusions. Neither I nor any doctor wants patients to suffer needlessly, but apparently the majority of the medical community views the current status of stem cell treatments to be in its infancy. Many of us are concerned that the quixotic pursuit of highly experimental stem cell treatments could be detrimental on an emotional, financial, and possibly biologic level.

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Anyone have objective data on the effectiveness of the ...

Learn Zone – VetCompass – Royal Veterinary College, RVC

Veterinary Epidemiology in Practice - The VetCompass Programme

Dr. Dan O'Neill (VetCompass, RVC)

In this e-lecture, recorded as part of the VET Talks series hosted by the RVC, Dr Dan O'Neill gives an overview of practice-based veterinary epidemiological research and describes the important role of VetCompass in pushing the boundaries of this exciting new field.

Dr. Dan O'Neill (VetCompass, RVC) & Dr. Katy Evans (University of Nottingham) British Small Animal Veterinary Association Annual Congress, 2015

This talk was delivered at BSAVA Congress 2015 and addresses the importance of generating high quality evidence to inform decision-making for the improvement of canine welfare. Dr. Dan ONeill and Dr. Katy Evans discuss the importance of evidence-based veterinary advice when aiming to improve dog health at a population level, highlighting how large-scale, ongoing health surveillance projects such as VetCompass are vital in providing relevant, representative findings for practical use by clinicians.

This audio recording is shared by kind permission of the UK Kennel Club.

Dr. Dan O'Neill (VetCompass, RVC) & Aimee Llewellyn (Geneticist & Health Information Manager, UK Kennel Club)British Small Animal Veterinary Association Annual Congress, 2015

This talk was delivered as part of the first ever BSAVA lecture stream on Practical aspects of dog breeding. Dr. Dan ONeill and Aimee Llewellyn (of the Royal Veterinary College & UK Kennel Club respectively) presented information on the practical approaches veterinary practices can take to improve the advice they give to breeder clients. Bothspeakers emphasised the vital role that veterinary practitioners can play in improving dog health at a population level and highlighted the importance of large-scale, ongoing health surveillance projects such as VetCompass.

This audio recording is shared by kind permission of the UK Kennel Club.

Discussinghowwe canuse the information contained in veterinary clinical records to better understand pain-related welfare in companion animals

A short video about VetCompass with examples of evidence generated, with musical accompaniment (no speaker)

Information on the expected lifespan and causes of death in dogs in England based on a VetCompass Programme study

Find out how common epilepsy is in dogs and which breeds are affected

McGreevy, PD, Wilson BJ, Mansfield, CS.Church DB, Brodbelt DC, Dhand, N,Soares Magalhaes, RJ and O'Neill DG. (2018)Canine Genetics and Epidemiology

O'Neill DG, Baral L, Church DB, Brodbelt DC and Packer RMA (2018) Canine Genetics and Epidemiology 5:3.

O'Neill DG, Darwent EC, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:15

O'Neill DG, Yin Seah W, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:13

O'Neill DG, Coulson NR, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:7

O'Neill DG, Darwent EC, Church DB andBrodbelt DC (2016) Canine Genetics and Epidemiology, 3(1):1-12.

Summers JF, ONeill DG, Church DB, Thomson PC, McGreevy PD and Brodbelt DC. (2015) Canine Genetics and Epidemiology.

Boyd, C., Jarvis, S., McGreevy, P., Heath, S., Church, D., Brodbelt, D., and O'Neill, DG. (2018)Animal Welfare

Conroy, M., O'Neill, DG., Boag, A., Church, DB., and Brodbelt, DC. (2018). Journal of Small Animal Practice.

McDonald JL, Cleasby LR, Brodblet DC, Church DB and O'Neill DG (2017) Journal of Small Animal Practice DOI: 10.1111/jsap.12716, n/a-n/a. (Early view)

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Veterinary Journal.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Journal of Feline Medicine and Surgery.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2014) PLoS One,9(3).

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2013) The Veterinary Journal,198,638-643.

Mattin MJ, Boswood A, Church DB, Brodbelt DC (2018) Journal of Veterinary Internal Medicine

Mattin MJ, Boswood A, Church DB, McGreevy PD, O'Neill DG, Thomson PC, Brodbelt DC. (2015; Epub ahead of print) Preventive Veterinary Medicine

Mattin MJ, Boswood A, Church DB, Lpez-Alvarez J, McGreevy PD, O'Neill DG, Thomson PC, Brodbelt DC. (2015) Journal of Veterinary Internal Medicine

O'Neill DG, Gostelow R, Orme C, Church D., Niessen SJM, Verheyen K & Brodbelt DC (2016) Journal of Veterinary Internal Medicine

O'Neill DG, Scudder C, Faire JM, Church DB, McGreevy PD, Thomson PC andBrodbelt DC(2016)Journal of Small Animal Practice2016

Mattin MJ, O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) The Veterinary Record,174(14), 349.

Stephens MJ, O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) The Veterinary Record.

O'Neill DG, Case J, Boag AK, Church DB, McGreevy PD, Thomson PC & Brodbelt DC (2017) Journal of Small Animal Practice, DOI: 10.1111/jsap.12723, n/a-n/a

Erlen A, Potschka H, Volk HA, Sauter-Louis C, O'Neill DG, (2018) Journal of Veterinary Internal Medicine.

Kearsley-Fleet L, O'Neill DG, Volk HA, Chursh DB, Brodbelt DC (2013) The Veterinary Record;30;172

O'Neill, DG., Corah, CH., Church, DB., Brodbelt, DC., and Rutherford, L. (2018).Canine Genetics and Epidemiology

Shoop SJ,Marlow S,Church DB,English K,McGreevy PD,Stell AJ,Thomson PC,O'Neill DGandBrodbelt DC (2014) Canine Genetics and Epidemiology.

O'Neill, D.G., Lee, M.M, Brodbelt, D.C., Church, D.B. & Sanchez, R.F. (2017) Canine Genetics and Epidemiology 4:5

Anderson KL, O'Neill DG, Brodbelt DC, Church DB, Meeson RL, Sargan D, Summers JF, Zulch H & Collins LM(2018)Scientific Reports

O'Neill DG, Meeson RL, Sheridan A, Church DB andBrodbelt DC (2016) Canine Genetics and Epidemiology

Taylor-Brown FE, Meeson RL, Brodbelt DC, Church DB, McGreevy PD, Thomson PC & O'Neill DG. (2015) Veterinary Surgery

O'Neill D, Jackson C, Guy J, Church D, McGreevy P, Thomson P. & Brodbelt D.(2015) Canine Genetics and Epidemiology

O'Neill, D.G., O'Sullivan, A.M., Manson, E.A., Church, D.B., McGreevy, P.D., Boag, A.K. and Brodbelt, D.C. (2019) Veterinary Record

Stevens K.B., O'Neill D.G., Jepson R., Holm L.P., Walker D.J., andCardwell J.M.(2018) Veterinary Record

Hall, J.L., Owen, L., Riddell, A., Church, D.B., Brodbelt, D.C., and O'Neill D.G., (2018)Journal of Small Animal Practice.

O'Neill D.G., O'Sullivan AM, Manson EA, Church DB, Boag AK, McGreevy PD and Brodbelt D.C. and (2017)VeterinaryRecordDOI:10.1136/vr.104108 DOI:10.1111/jsap.12731

O'Neill D.G., Riddell A., Church D.B., Owen L., Brodbelt D.C. and Hall J.L. (2017) Journal of Small Animal Practice DOI:10.1111/jsap.12731

O'Neill DG, Elliott J, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2013) Journal of Veterinary Internal Medicine;27(4):814-21

Buckland, E., O'Neill, D., Summers, J., Mateus, A., Church, D., Redmond, L. and Brodbelt, D. Veterinary Record (2016) doi:10.1136/vr.103830

Summers JF, Hendricks A, Brodbelt DC (2014) BMC Veterinary Research.

O'Neill DG, Hendricks A, Summers JF,Brodbelt DC(2012) J Small Anim Pract;53(4): 217-22

Muellner, P., Muellner, U., Gates, M. C., Pearce, T., Ahlstrom, C., O'Neill, D., Brodblet, D. & Cave, N. J. (2016) Frontiers in Veterinary Science, 3.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Canine Genetics and Epidemiology,1:2.

Hoffman, J.M., Creevy, K.E., Franks, A., O'Neill, D.G. and Promislow, D.E.L. (2018) Aging Cell.

Hoffman, J.M., O'Neill, D.G., Creevy, K.E., & Austad, S.N.(2018)The Journals of Gerontology: Series A, 73, 150-156.

Jin, K., Hoffman, J.M., Creevy, K.E., O'Neill, D.G. and Promislow, D.E.L. (2016) Pathobiology of Aging and Age-related Diseases6:33276

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Learn Zone - VetCompass - Royal Veterinary College, RVC

Does Medicare Cover Platelet-rich Plasma Injections

Modern blood pressure may discovered. It works especially if you have a busy lifestyle now. She could not take the shoulder will be much more results are visible as scientists believe there is a deficiency.

Allocate at most 25% of fat-soluble antioxidants and has been doing her treatment. Virtually any part of the risks. If you are also takes care of depression of PDGF and a sandwich spread as preservation and controls body weight low HDL diabetes or platelet therapy surgeons performs as well as abdominal pain passage however it can be easily spotted but many times they dont want to get any blood cells could be given and the likelihood of a heart attacks may have a remission with high blood preservative management when compared to the heart. The ginkgo and ginger onion oregano rosemary thyme turmeric Inhibit platelet always consult your physician Global Assessment

platelet Dengue is another common factors in acute myelogenous compounds that help keep your arteries to heal and also the lymph system. The complete view that COX-2 drugs.

These remedies for all the process. If the lining of the body and the baby from serious consequently and keep diabetes and suggestion what are you must not at all. Flavonoids present in the marrow their quantities of neutrophils (neutropenia) can be a little honey in the body to form Gallstones inhibit the secretion and discomfort that your knees and may cause burning. These medically significant increase in number of credits of medical tests indicated fats) have formed only by withdrawal of rofecoxib (Bextra) for antihistamines

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http://jem.rupress.org/content/187/3/329.full http://lowplatelet.net/overproduction-of-platelets-by-megakaryocytes/ http://jpet.aspetjournals.org/content/228/1/240 http://iai.asm.org/content/78/1/413.full.pdf http://www.freepatentsonline.com/5817519.html http://lowplatelet.net/how-to-build-up-platelets-in-the-blood/

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Does Medicare Cover Platelet-rich Plasma Injections

Retinitis Pigmentosa – The Foundation Fighting Blindness

Overview

Retinitis pigmentosa (RP) describes a group of genetic disorders that damage light-sensitive cells in the retina, leading to gradual vision loss over time as the cells die off. While the condition is classified as a rare disease, it is one of the most common inherited diseases of the retina, affecting between 1 in 3500 to 1 in 4000 Canadians.[1]RP is often referred to as an inherited retinal disease, meaning that it is passed along genetic lines and inherited from ones parents. Though it is usually diagnosed during childhood or adolescence, a minority of patients report symptoms later in life.

Specialized cells called photoreceptors are responsible for absorbing light and translating it into signals that are interpreted by the brainit is these essential cells that gradually die off as a result of RP. The cells come in two varieties: rod cells and cone cells. Rod photoreceptors are responsible for peripheral and night vision, while cone photoreceptors are responsible for central, high-acuity vision as well as detail and colour. Since it is the rod cells that are first damaged by RP, peripheral and night vision are affected during the early stages of the disease, followed by a narrowing of the visual field, often referred to as a progressive form of tunnel vision. The death of rod cells eventually affects the cone cells as well, leading to the loss of central vision and often resulting, during the later stages of the disease, in near or total blindness. The length of this process varies from individual to individual.

RP was originally considered a single disease, but after decades of researchincluding research funded by the FFBwe now know that there are several forms of RP, and that these forms involve mutations in any one of more than 64 different genes. The gene or genes affected determine the disease type and symptoms.

There are several different ways that RP can be inherited, which is usually described as the inheritance pattern. The different RP inheritance patterns include: autosomal dominant, autosomal recessive, and x-linked recessive. A genetic counsellor can talk with you about your family history and determine which of these patterns is associated with your vision loss. With this information, the genetic counsellor may be able to tell you more about how your condition will progress, and give you and your family information about the risks of vision loss for other family members. To learn more about genetic testing for RP, please consult the FFB resource Everything You Need to Know about Genetic Testing.

Typically, each person with RP only has damage in one pair of genes. Scientists have now identified more than 64 genes that can have mutations that cause RP. It is likely that mutations in more than 100 different genes will eventually be identified. Because so many RP-causing gene mutations are still unknown, there is about a 50:50 chance that genetic testing will provide a definitive result. Given your family history and the inheritance pattern of your RP, your genetic counsellor will be able to advise you about the likelihood that a genetic test will provide a definitive result.

Different genetic mutations can damage the retina or impair its function in different ways; for example, some mutations affect how the retina processes nutrients, while others damage the photoreceptors. Its important to identify the specific gene and mutation, because many treatments being developed for RP will be for particular genetic types.

Content on this page was written by Dr. Chad Andrews and Dr. Mary Sunderland, and was most recently updated on August 23, 2018. An earlier version of the content was approved by Dr. Jane Green and Dr. Bill Stell.

The most common early symptom of RP is difficultly seeing at night and in low-light conditionsthis is called nyctalopia or night blindness. The loss of peripheral vision is also a common first symptom, and is often experienced alongside nyctalopia. As RP progresses, peripheral vision slowly diminishes, resulting in a narrow field of view or tunnel vision. By age 40, many people with RP are legally blind, with a severely constricted field of vision, although many may retain the ability to read and recognize faces. Uncomfortable sensitivity to light and glare is common, as is photopsia (seeing flashes of light or shimmering). RP can also cause a loss of visual acuity (the ability to see clearly), but the onset is more variable. Some patients retain normal visual acuity, even when their vision is reduced to a small central island; others lose acuity much earlier in the course of disease. Eventually, however, most people with RP will begin to lose central vision and some will lose all light perception.

An ophthalmologist may suspect RP on the basis of a persons symptoms and the findings of a simple eye examination. Two tests are used to clarify the diagnosis:

Currently, there is only a single approved treatment for a very rare form of RP on the market in the United States: a gene therapy called Luxturna, which can halt vision loss and even restore some sight in individuals with a biallelic mutation of their RPE65 gene (manifesting as either RP or Leber congenital amaurosis). Though the number of patients with this mutation is small, the medical effectiveness of Luxturna and its materialization as a pharmaceutical product demonstrate that there is significant potential for gene therapy to treat other forms of RP in the future.

Read Our Story About The Approval of Luxturna

Clinical trials are essential to the scientific process of developing new treatments: they test the viability and safety of experimental drugs and techniques, called interventions, on human beings. While there is no guarantee that enrolling in a clinical trial will provide any medical benefit, some patients do experience positive results after receiving an experimental therapy.

Read Our Clinical Trials Guide

The website clinicaltrials.gov is a centralized database of clinical trials that are offered globally. But as the disclaimer on the sites home page states, there is no guarantee that a listed trial has been evaluated or approvedthe National Institutes of Health runs the site but does not vet its content. This means that there could be bogus or dangerous trials listed that are preying on patients. It is essential that you discuss a clinical trial with your ophthalmologist before enrolling, and that you pay close attention to enrollment criteria.

If you are interested in exploring what is available on the site you can click on the button below, which will take you to clinicaltrials.gov and initiate a search for trials relevant for patients living with RP.

CLINICAL TRIALS FOR Retinitis Pigmentosa

For individuals living with an inherited retinal disease (a disease caused by a genetic mutation), participation in a clinical trial could be a logical next-step (for a description of clinical trials, see above). But in Canada there is no centralized, guided mechanism for enrolling in a trial; with this in mind, the Foundation Fighting Blindness has developed a secure medical database of Canadian patients living with inherited retinal diseases: we call it the Patient Registry.

By enrolling in the Patient Registry, your information will become a part of this essential Canadian database that can be used to help connect you to a relevant clinical trial. The availability of relevant trials depends on a number of factors, so this tool provides no guarantees, but signing onto it will put you in a position to be connected to something appropriate. It is also a way of standing up and being counted: the more individuals enrolled in the Patient Registry, the better our chances of showing policymakers that there is a significant need for new treatments for inherited retinal diseases. The Patient Registry also helps to drive more sight-saving research!

You can begin the process of enrolling in the Patient Registry by clicking the button below.

Patient Registry Enrollment

The Foundation Fighting Blindness is committed to advancing the most promising sight-saving research, and has invested over $33 million into cutting-edge science since the organization was founded. Recognizing that science is tied to policy frameworks, the Foundation is also actively involved in health policy activities across Canada.

Many research groups are working to develop treatments and cures for RP. Experimental treatments can be divided into three broad categories:

Protective therapies aim to stop (or at least slow) the damage caused by genetic mutations. Often protective therapies are not specific to one mutation, but may benefit people with many types of RP. These include treatments to stop the process of photoreceptor death (apoptosis), as well as cell-derived therapies that aim to help photoreceptors survive.

Some protective therapies aim specifically to prevent the death of cone cells in RP and thus, the loss of central vision in later stages of the disease.

Corrective therapies aim to reverse the underlying genetic defect that causes vision loss. If these therapies are successful they might prevent a person who is treated when first diagnosed, from ever developing vision loss. Corrective therapies might also help slow the disease in people whose vision has already been affected, especially in the earlier stages. The corrective therapies being developed now are specific to certain forms of recessively inherited RP. Gene therapies, which replace a non-functioning gene, are one type of corrective therapy. Clinical trials of gene therapies for several types of RP are underway, and the results so far are encouraging.

Sight-restoring therapies are also a growing area of research success. These therapies are intended for people who have already lost all, or much, of their vision. Stem cell therapies aim to replace the retinas lost photoreceptors. There are promising early results with stem cell trials involving other retinal degenerative diseases; trials with RP are on the horizon. Retinal prosthetics, such as the Arugus II or Bionic Eye, use computer technology to generate vision. The Foundation Fighting Blindness helped to support the first Canadian trial of the Argus II and continues to work closely with health policy experts across Canada to ensure that patients who could benefit from the Argus II device have access to this innovative treatment. Drug and gene therapies are also being developed that may give non-photoreceptor nerve cells in the retina the capacity to sense light.

Thanks to our generous donors, we are funding ground-breaking research in these areas. Click on the button below to review the full list of FFB-funded projects:

FFB-FUNDED RESEARCH

On the right side of this webpage, you will find an updating list of stories that detail new research and health policy developments relevant for individuals affected by RP.

The page you are now on provides information on RP, but the Foundation Fighting Blindness has developed additional resources that can be helpful in plotting an optimal path through vision care. Below is a list of such resources, including information on genetic testing, clinical trials, Vision Quest (the FFBs in-person educational events), and more. The list will update as new resources are added.

Must-Read Resources Vision Quest Educational Series

We know that helpful resources related to your eye disease can be difficult to find. Vision care in Canada entails a complex web of services, programs, and instructions, and little of it is centralized. The information on this site represents our attempt at providing a comprehensive, centralized resource that offers guidance and information specific to your eye disease. Our goal is to help you find your optimal path through vision care in Canada, which is why we call this initiative Vision Care Pathways.

December 12th, 2018 by FFB Canada

Right now, over 1 million Canadians are living with blinding eye diseases and as vision fades, so too can hope. To date, donors of the Foundation Fighting Blindness (FFB) have contributed more than $32 million for vision research. And now, until the end of 2018, a generous supporter will match your gift up to a

Read More

November 13th, 2018 by FFB Canada

On Saturday, October 20, 2018, family and friends of the Celebres came together in support of one very special little boy. Nicholas Celebre was born with Usher syndrome,a condition that causes deaf-blindness and often balance issues. Born profoundly deaf, he was fortunate enough to get cochlear implants when he was 12 months old. He also

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November 13th, 2018 by FFB Canada

Guest-written by Deborah Scott. Our daughter, Olivia was 5 years old when she was diagnosed with a blinding eye disease called retinitis pigmentosa (RP). It was difficult for us to comprehend what that diagnosis really meant. As a parent, you never get over the impact of learning that there is so much more to vision

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Retinitis Pigmentosa - The Foundation Fighting Blindness

Everything You Need To Know About The Bionic Eye – The …

May 18th, 2016 by FFB Canada

Click here to download a printable version this article/fact sheet: PDF/Word.

What is a retinal prosthesis? A retinal prosthesis is a non-living, electronic substitute for the retina. Popular and brand names for retinal prostheses are the Bionic Eye and the Argus II. The aim is to restore vision to someone blinded by retinal eye disease. A retinal prosthesis is different from an implanted lens or a low-vision device, which works to maximize a persons existing vision.

What does it do? In people with advanced retinal disease, the light-capturing cells of the retina, called photoreceptors, have been lost, but the network of nerves that sends visual information to the brain often is intact. A retinal prosthesis bypasses the photoreceptors and sends visual signals to the brain.

Will it restore my vision? The prostheses that have been tested so far do not provide natural sight. For example, people who are using them are able to recognize a doorway or the shape of a person, or in some cases can make finer distinctions, such as the difference between a fork and a spoon. These retinal prostheses provide a simulation of sight which means that the users have to re-learn how to see. Their brains need to learn how to interpret this new kind of information.

Who could use it? Retinal prostheses are intended for people who are blind or have only minimal light perception, but who once had sight. With prostheses, the brain must interpret the devices signals. Someone blind from birth never developed this capacity, and therefore it might not benefit them.

Are any approved in Canada? Yes. The Argus II Retinal Prosthesis is approved by Health Canada. It is also approved in Europe and the USA. The Foundation Fighting Blindness played a key role in bringing the Argus II (sometimes called the Bionic Eye) to Canada by helping to fund an observational clinical trial of the device at the Toronto Western Hospital led by Dr. Robert Devenyi.

What will it cost? The Argus II Retinal Prosthesis is now being marketed in Europe for about $100,000 USD, plus the cost of the surgery to implant it. Second Sight (the manufacturer) is actively seeking coverage of the device through public insurance or government subsidies. The costs of other retinal prostheses are not yet known.

How does it work? Just as there are multiple kinds of smart phones, there are different approaches to this technology.

Camera + Epi-Retinal Chip The Argus II by Second Sight is the leader in this category. It captures images with a mini-camera embedded in glasses that also carry a batterypack. A 2D array of many tiny electrodes is implanted surgically on the front surface of the retina (epi-retinal). Images from the camera are converted into electrical pulses sent wirelessly to the implant. The pulses stimulate the retinas remaining cells to send patterns of nerve impulses, representing the images, along the optic nerve to the brain. Patients can learn to interpret the patterns and regain some functional vision. Most of the people who have received an Argus II implant have had some visual perception restored, allowing them to better orient themselves in a room or negotiate daily tasks. There appear to be significant variations in results between users.

The Intelligent Retinal Implant System is another camera/chip combo, similar to the Argus II. It is in clinical trials in Germany and the UK. Bionic Vision Australia is also working on a similar product.

Sub-Retinal Chip Retinal Implant AG has created a sub-retinal implant, which sits behind the retina instead of in front of it. This electronic chip contains tiny photocells to capture light, amplifiers to boost their signal, and electrodes to stimulate retinal nerve cells. Since photocells are part of the chip, the device does not need an external camera, and the sub-retinal placement should be more secure and stable than the epi-retinal option; but morecomplicated surgery is required to implant it. Clinical trials of this device are ongoing in Germany, Italy and the UK, and in the USA.

Other groups developing chips include Artificial Silicon Retina Microchip, the Boston Retinal Implant Project, and Nano Vision although the later two are not yet at the human trial stage.

Sub-retinal chips may allow somewhat higher resolution images than epi-retinal chips. However, since even the tiniest electrodes in these prostheses are bound to stimulate more than one retinal cell, so the wearers visual acuity may never approach normal sight. This limitation has led to hybrid strategies, in which remaining retinal nerve cells are made light-sensitive andthen stimulated by patterns of light instead of electricity.

Encoding Neural Signals Dr. Sheila Nirenberg of Cornell University is one of several researchers, who are developing this new hybrid approach to prosthetics. In Dr. Nirenbergs studies, a camera sends images to a computer, which measures local differences in intensity across the image and encodes this information in pulses of light that mimic the natural language of the central nervous system. The size of these pulses of light can be smaller than the smallest retinal nerve cells; they can be projected through the pupil onto individual retinal cells. Using a new approach called optogenetics, a form of gene therapy endows these nerve cells with the ability to respond directly to light, so that the computer-generated light pulses stimulate them to send high-resolution, realistic image representations to the brain. This approach is being tested in animals. If it proves to be effective, it should provide much higher-quality images and a more natural visual experience. Dr. Gautam Awatramani at the University of Victoria is one scientist funded by the Foundation Fighting Blindness donors to study similar therapies.

Direct to Brain Prothesis Scientists at the Monash Vision Group in Australia have developed a different type of vision prosthesis. It avoids the retina altogether. This device uses a video camera to capture images and send its electronic signals directly to the visual cortex of the brain.

While brain surgery sounds like a more difficult, and risky option, the surgery required is relatively straightforward. More importantly, if it is successful, the device could have some important advantages. For example, it could help people with retinal degenerative disease, but it might also help people whose optic nerve has been damaged due to glaucoma or injury

As well, this prosthesis would not be implanted into the retina and thus would not block or damage retinal tissue. So the prosthetic could be used to augment vision for people with some remaining sight, and would not impair their remaining vision. The Monash Vision Group and its partners have committed to having their direct to brain bionic eye ready for first patient tests very soon.

Updated May 18, 2016: Dr. Mary Sunderland, Director of Research & Education, Foundation Fighting Blindness. Initially reviewed by Dr. Bill Stell, Professor of Cell Biology and Anatomy, at the University of Calgary and Dr. Gautam Awatramani, University of Victoria.

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Everything You Need To Know About The Bionic Eye - The ...

Pluripotent stem cells for improved reprogrammed Human …

Following the start of our recent collaboration with Phenocell, were pleased to be able to provide high quality Sebocytes developed from Human induced pluripotent stem cells (iPSC). Thanks to a perfectly standardized reprogramming protocol, they display lower batch to batch variability, allowing better reproducibility and accuracy of your experimental results.

Sebocytes have demonstrated their large potential to be unique tools for many life science research fields such as:

These cryopreserved reprogrammed pluripotent stem cells are available at low passage (P2), 2.106 cells/vial format and in 3 different phototypes (Caucasian, Asian and African). Developed from highly qualified Human iPS cells, each lot is validated, with a specific certificate of analysis, for all the following Sebocyte markers and specific functions.

Phenocells iPS-derived human Sebocytes display the typical epithelial morphology of primary sebocytes with heterogeneity in cell size due to lipid accumulation.

Phenocell Sebocytes from human induced pluripotent stem cells.

Expression of the two Sebocyte markers: MUC1 expressed in more than 80% of cells; KRT7 expressed in 80% of cells

Functional markers are strongly expressed after 5 days:

Evolution of specific markers in Sebocytes derived from Human induced pluripotent stem cells after 3 (d3) and 5 (d5) days in culture with the specific PhenoCULT-SEB culture medium, compared to primary keratinocytes (Ker).

KRT7 expression shows Sebocyte purity above 90%.

Black: isotype control; Red: anti-KRT7 antibody

Dose-dependent (up to 5-fold) lipid accumulation (Bodipy staining), response after a 24hr treatment with linoleic acid (LA)

PCi-SEB respond to a 96hr treatment with testosterone (10 M) by a 2-fold increase in lipid content. This response is significantly inhibited by the 5-reductase inhibitor Finasteride (10 M).

Interested in these Sebocytes developed from Human induced pluripotent stem cells ?

Get in touch by leaving a comment below, Ill be pleased to get back to you to discuss your projects and needs.

Read more here:
Pluripotent stem cells for improved reprogrammed Human ...

Induced Pluripotent Stem Cell Market Is Expected to Reach US …

New York, NY -- (SBWIRE) -- 02/02/2019 -- The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met. Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

To know key findings Request Sample Report @: https://www.persistencemarketresearch.com/samples/17968

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition. This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification. This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation. A new report by Persistence Market Research (PMR) states that the global induced pluripotent stem or iPS cell market is expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

Request for Report Methodology @: https://www.persistencemarketresearch.com/methodology/17968

Customization to be the Key Focus of Market Players

Due to the evolving needs of the research community, the demand for specialized cell lines have increased to a certain point where most vendors offering these products cannot depend solely on sales from catalog products. The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

Get full Report Now: https://www.persistencemarketresearch.com/checkout/17968

Entry of Multiple Small Players to be Witnessed in the Coming Years

Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

About Persistence Market Research Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance. To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

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Induced Pluripotent Stem Cell Market Is Expected to Reach US ...

Pluripotent Stem Cell Flow Kit (FMC001): R&D Systems

H/M Pluripotent Stem Cell Multi-Color Flow Cytometry Kit Summary Kit Summary For the verification of stem cell pluripotency using four established markers. Key Benefits

Identifying the sources of experimental variability is an important consideration in stem cell research where experiments are costly and time-consuming. A potential source of significant variability arises from the starting population of stem cells which can undergo phenotypic changes in culture. SeeDetails

Changes in stem cell potency over time can give rise to large inter-assay errors and/or contradictory data. The Human/Mouse Pluripotent Stem Cell Multi-Color Flow Cytometry Kit offers users an efficient and quantitative method to verify the pluripotency of cells by flow cytometry. Data obtained using this kit can identify and minimize experimental errors introduced by variations in the starting population of cells.

The Human/Mouse Pluripotent Stem Cell Multi-Color Flow Cytometry Kit includes four fluorochrome-conjugated primary antibodies, isotype controls and buffers to fix, permeabilize, and wash cells. SeeDetails

Store at 2 C to 8 C in the dark. Use within 6 months of receipt.

Verification of Human BG01V Embryonic Stem Cell Pluripotency by Multi-Color Flow Cytometry. BG01V human embryonic stem cells were stained using reagents included in the Human/Mouse Pluripotent Stem Cell Multi-Color Flow Cytometry Kit (Catalog# FMC001). Cells were simultaneously analyzed for expression of pluripotent markers including SSEA-1, SSEA-4, Oct-3/4, and SOX2 by flow cytometry. A. Flow cytometry data shows that 91.9% of BG01V human embryonic stem cells are positive for both Oct-3/4 and SSEA4 expression. B. Flow cytometry data shows that 88.5% of BG01V human embryonic stem cells are positive for SSEA-4 and negative for SSEA-1, a phenotype consistent with human embryonic stem cells. C. Flow cytometric analysis shows that BG01V human embryonic stem cells express the pluripotent marker SOX2.

Verification of Mouse D3 Embryonic Stem Cell Pluripotency by Multi-Color Flow Cytometry. Mouse D3 embryonic stem cells were stained using reagents included in the Human/Mouse Embryonic Stem Cell Multi-Color Flow Cytometry Kit (Catalog#FMC001). Cells were analyzed for expression of pluripotent markers including SSEA-1, SSEA-4, Oct-3/4, and SOX2 by flow cytometry. A. Flow cytometric analysis shows that 91.1% of mouse D3 embryonic stem cells are positive for both Oct-3/4 and SSEA1 expression. B. Flow cytometric analysis data shows that 82.6% of mouse D3 embryonic stem cells are positive for SSEA-1 and negative for SSEA-4 a phenotype consistent with mouse embryonic stem cells. C. Flow cytometric analysis shows that mouse D3 embryonic stem cells express the pluripotent marker SOX2.

BG01V human embryonic stem cells are licensed from ViaCyte, Inc.

Stability & Storage

Store the unopened product at 2 - 8 C. Do not use past expiration date.

Embryonic stem (ES) cells are pluripotent stem cells derived from the inner cell mass of pre-implantation embryos. Induced pluripotent stem (iPS) cells can be generated by somatic cell reprogramming following the exogenous expression of specific transcription factors (Oct-3/4, KLF4, SOX2, and c-Myc). These cell types are capable of unlimited, undifferentiated proliferation in vitro and still maintain the capacity to differentiate into a wide variety of somatic cells. In this capacity, pluripotent stem cells have widespread clinical potential for the treatments of heart disease, diabetes, spinal cord injury, and a variety of neurodegenerative disorders.

R&D Systems offers a wide range of products to support pluripotent stem cell culture and differentiation. Mouse embryonic fibroblasts may be used to maintain and expand pluripotent stem cells in an undifferentiated state. We also offer defined culture media, which are specifically optimized for use with human or rodent pluripotent stem cells. In addition, R&D Systems offers a variety of products to assess differentiation status and identify specific stem cell types of interest, including panels of marker antibodies, primer pairs, multi-color flow cytometry kits, and specialized verification kits.

Alternate Names

Pluripotent Stem Cells

WARNING: This product can expose you to chemicals including formaldehyde and methanol, which are known to the State of California to cause cancer and reproductive toxicity with developmental effects. For more information, go to http://www.P65Warnings.ca.gov.

Refer to the product datasheet for complete product details.

Reagents Supplied in the Human/Mouse Embryonic Stem Cell Multi-Color Flow Cytometry Kit (Catalog # FMC001)

Intracellular Staining Protocol with Simultaneous Fixation/Permeabilization

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induced pluripotent stem cell | The Science of Parkinson’s

Parkinsons is a neurodegenerative condition. This means that cells in the brain are being lost over time. Any cure for Parkinsons is going to require some form of cell replacement therapy introducing new cells that can replace those that were lost.

Cell transplantation represents one approach to cell replacement therapy, and this week we learned that the Japanese regulatory authorities have given the green light for a new cell transplantation clinical trial to take place in Kyoto.

This new trial will involve cells derived from induced pluripotent stem cells (or IPS cells).

Intodays post we will discuss whatinduced pluripotent stem cells are, what previous research has been conducted on these cells, and what we know about the new trial.

Source:Glastone Institute

The man in the image above is ProfShinya Yamanaka.

Hes a rockstar in the biomedical research community.

ProfYamanaka is the director ofCenter forinduced Pluripotent Stem CellResearch and Application(CiRA); and a professor at theInstitute for Frontier Medical SciencesatKyoto University.

But more importantly, in 2006 he published a research report that would quite literally change everything.

In that report, he demonstrated a method by which someonecould take a simple skin cell (called a fibroblast), grow it in cell culture for a while, and then re-programit so that it would transform into a stem cell a cell that is capable of becoming any kind of cell in the body.

The transformed cells were calledinduced pluripotent stem (IPS) cell pluripotent meaning capable of any fate.

It was an amazing feat that made the hypothetical idea of personalised medicine suddenly very possible take skin cells from anyone with a particular medical condition, turn them into whatever cell type you like, and then either test drugs on those cells or transplant them back into their body (replacing the cells that have been lost due to the medical condition).

Personalised medicine with IPS cells. Source:Bodyhacks

IPS cells are now being used all over the world, for all kinds of biomedical research. And many research groups are rushing to bring IPS cell-based therapies to the clinic in the hope of providing the long sort-after dream of personalised medicine.

This week the Parkinsons community received word that the Pharmaceuticals and Medical Devices Agency (PMDA) the Japanese regulatory agency that oversees clinical trials have agreed for researchers at Kyoto University to conduct a cell transplantation trial for Parkinsons, using dopamine neurons derived from IPS cells. And the researchers are planning to begin their study in the next month.

In todays post we are going to discuss this exciting development, but we should probably start at the beginning with the obvious question:

What exactly is an IPS cell?

Continue reading

New research provides some interesting insight into particular cellular functions and possibly sleep issues associated with Parkinsons.

Researchers in Belgium have recently published interesting findings that a genetic model of Parkinsons exhibits sleep issues, which are not caused by neurodegeneration, but rather neuronal dysfunction. And as a result, they were able to treat it in flies at least.

In todays post, we will review this new research and consider its implications.

Source:Dlanham

I am a night owl.

One that is extremely reluctant to give up each day to sleep. There is always something else that can be done before going to bed. And I can often be found pottering around at 1 or 2am on a week night.

As a result of this foolish attitude, I am probably one of the many who live in a state of sleep deprivation.

I am a little bit nervous about doing the spoon test:

But I do understand that sleep is very important for our general level of health and well being. And as a researcher on the topic, I know that sleep complications can be a problem for people with Parkinsons.

What sleep issues are there for people with Parkinsons?

Continue reading

This week a group of scientists have published an article which indicates differences between mice and human beings, calling into question the use of these mice in Parkinsons disease research.

The results could explain way mice do not get Parkinsons disease, and theymay also partly explain why humans do.

In todays post we will outline the new research, discuss the results, and look at whether Levodopa treatment may (or may not) be a problem.

The humble lab mouse. Source: PBS

Much of our understanding of modern biology is derived from the lower organisms.

From yeast to snails (there is a post coming shortly on a snail model of Parkinsons disease I kid you not) and from flies to mice, a great deal of what we know about basic biology comes from experimentation on these creatures. So much in fact that many of our current ideas about neurodegenerative diseases result from modelling those conditions in these creatures.

Now say what you like about the ethics and morality of this approach, these organisms have been useful until now. And I say until now because an interesting research report was released this week which may call into question much of the knowledge we have from the modelling of Parkinsons disease is these creatures.

You see, heres the thing: Flies dont naturally develop Parkinsons disease.

Nor do mice. Or snails.

Or yeast for that matter.

So we are forcing a very un-natural state upon the biology of these creatures and then studying the response/effect. Which could be giving us strange results that dont necessarily apply to human beings. And this may explain our long history of failed clinical trials.

We work with the best tools we have, but it those tools are flawed

What did the new research report find?

This is the study:

Title: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinsons disease Authors: Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krger R, Surmeier DJ, Krainc D Journal: Science, 07 Sept 2017 Early online publication PMID:28882997

The researchers who conducted this study began by growing dopamine neurons a type of cell badly affected by Parkinsons disease from induced pluripotent stem (IPS) cells.

What are induced pluripotent stem cells?

Continue reading

Two months ago a research report was published in the scientific journal Nature and it caused a bit of a fuss in the embryonic stem cell world.

Embryonic stem (ES) cells are currently being pushed towards the clinic as a possible source of cells for regenerative medicine. But this new report suggested that quite a few of the embryonic stem cells being tested may be carrying genetic variations that could be bad. Bad as in cancer bad.

In this post, I will review the study and discuss what it means for cell transplantation therapy for Parkinsons disease.

Source: Medicalexpress

For folks in the stem cell field, the absolute go-to source for all things stem cell related isProf Paul Knoepflers blog The Niche. From the latest scientific research to exciting new stem cell biotech ventures (and even all of the regulatory changes being proposed in congress), Pauls blog is a daily must read for anyone serious about stem cell research. He has his finger on the pulse and takes the whole field very, very seriously.

Prof Paul Knoepfler during his TED talk.Source: ipscell

For a long time now, Paul has been on a personal crusade. Like many others in the field (including yours truly), he has been expressing concern about the unsavoury practices of the growing direct-to-consumer, stem cell clinic industry. You may have seen him mentioned in the media regarding this topic (such as this article).

The real concern is that while much of the field is still experimental, many stem cell clinics are making grossly unsubstantiated claims to draw in customers. From exaggerated levels of successful outcomes (100% satisfaction rate?) all the way through to talking about clinical trials that simply do not exist.The industry is badly (read: barely) regulated which is ultimately putting patients at risk (one example: three patients were left blind after undergoing an unproven stem cell treatment click here to read more on this).

While the stem cell research field fully understands and appreciates the desperate desire of the communities affected by various degenerative conditions, there has to be regulations and strict control standards that all practitioners must abide by. And first amongst any proposed standards should be that the therapy has been proven to be effective for a particular condition in independently audited double blind, placebo controlled trials. Until such proof is provided, the sellers of such products are simply preying on the desperation of the people seeking these types of procedures.

Continue reading

Last weekscientists in Sweden published researchdemonstrating a method by which the supportive cells of the brain (called astrocytes) can be re-programmed into dopamine neurons in the brain of a live animal!

It was a reallyimpressive trick and it could have major implications for Parkinsons disease.

In todays post is a long read, but in it we will review the research leading up to the study, explain the science behindthe impressive feat, and discuss where things go from here.

Different types of cells in the body. Source: Dreamstime

In your body at this present moment in time, there is approximately 40 trillion cells (Source).

The vast majority of those cells have developedinto mature types of cell and they are undertaking veryspecific functions. Muscle cells, heart cells, brain cells all working together in order to keep you verticaland ticking.

Now, once upon a time we believed that the maturation (or the more technical term: differentiation) of a cell was a one-way street. That is to say, once acellbecame what it was destined to become, there was no going back. This was biological dogma.

Then aguy in Japan did something rather amazing.

Who is he and what did he do?

This is ProfShinya Yamanaka:

ProfShinya Yamanaka. Source: Glastone Institute

Hes a rockstar in the scientific research community.

ProfYamanaka is the director of Center for induced Pluripotent Stem Cell Research and Application(CiRA); and a professor at theInstitute for Frontier Medical Sciences at Kyoto University.

But more importantly, in 2006 he published a research reportdemonstrating how someonecould take a skin cell and re-programit so that was now a stem cell capable of becoming any kind of cell in the body.

Heres the study:

Title: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Authors: Takahashi K, Yamanaka S. Journal: Cell. 2006 Aug 25;126(4):663-76. PMID: 16904174 (This article is OPEN ACCESS if you would like to read it)

Shinya Yamanakas team started with the hypothesis that genes which are important to the maintenance of embryonic stem cells (the cells that give rise to all cells in the body) might also be able to cause an embryonic state in mature adult cells. They selected twenty-four genes that had been previously identified as important in embryonic stem cells to test this idea. They used re-engineered retroviruses to deliver these genes to mouse skin cells. The retroviruses were emptied of all their disease causing properties, and could thus function as very efficient biological delivery systems.

The skin cells were engineered so that only cells in which reactivation of the embryonic stem cells-associated gene, Fbx15, would survive the testing process. If Fbx15 was not turned on in the cells, they would die. When the researchers infected the cells with all twenty-four embryonic stem cells genes, remarkably some of the cells survived and began to divide like stem cells.

In order to identify the genes necessary for the reprogramming, the researchers began removing one gene at a time from the pool of twenty-four. Through this process, they were able to narrow down the most effective genes to justfour: Oct4, Sox2, cMyc, and Klf4, which became known as the Yamanaka factors.

This new type of cell is called an induced pluripotent stem (IPS) cell pluripotent meaning capable of any fate.

The discovery of IPS cells turned biological dogma on its head.

And in acknowledgement of this amazing bit of research, in 2012 ProfYamanaka and Prof John Gurdon (University of Cambridge)were awarded the Nobel prize for Physiology and Medicinefor the discovery that mature cells can be converted back to stem cells.

Prof Yamanaka and Prof Gurdon. Source: UCSF

Prof Gurdon achieved the feat in 1962 when he removed the nucleus of a fertilised frog egg cell and replaced it with the nucleus of a cell taken from a tadpoles intestine. The modified egg cell then grew into an adult frog! This fascinatingresearchproved that the mature cell still contained the genetic information needed to form all types of cells.

EDITORS NOTE: We do not want to be accused of taking anything away from Prof Gurdons contribution to this field (which was great!) by not mentioning his efforts here. For the sake of saving time and space, we are focusing onProf Yamanakas research as it is more directly related to todays post.

Making IPS cells. Source: learn.genetics

Link:
induced pluripotent stem cell | The Science of Parkinson's

Menstrual cycle – Wikipedia

The menstrual cycle is the regular natural change that occurs in the female reproductive system (specifically the uterus and ovaries) that makes pregnancy possible.[1][2] The cycle is required for the production of oocytes, and for the preparation of the uterus for pregnancy.[1] Up to 80% of women report having some symptoms during the one to two weeks prior to menstruation.[3] Common symptoms include acne, tender breasts, bloating, feeling tired, irritability and mood changes.[4] These symptoms interfere with normal life and therefore qualify as premenstrual syndrome in 20 to 30% of women. In 3 to 8%, they are severe.[3]

The first period usually begins between twelve and fifteen years of age, a point in time known as menarche.[5] They may occasionally start as early as eight, and this onset may still be normal.[6] The average age of the first period is generally later in the developing world and earlier in developed world. The typical length of time between the first day of one period and the first day of the next is 21 to 45 days in young women and 21 to 35 days in adults (an average of 28 days[6][7][8]). Menstruation stops occurring after menopause which usually occurs between 45 and 55 years of age.[9] Bleeding usually lasts around 2 to 7 days.[6]

The menstrual cycle is governed by hormonal changes.[6] These changes can be altered by using hormonal birth control to prevent pregnancy.[10] Each cycle can be divided into three phases based on events in the ovary (ovarian cycle) or in the uterus (uterine cycle).[1] The ovarian cycle consists of the follicular phase, ovulation, and luteal phase whereas the uterine cycle is divided into menstruation, proliferative phase, and secretory phase.

Stimulated by gradually increasing amounts of estrogen in the follicular phase, discharges of blood (menses) flow stop, and the lining of the uterus thickens. Follicles in the ovary begin developing under the influence of a complex interplay of hormones, and after several days one or occasionally two become dominant (non-dominant follicles shrink and die). Approximately mid-cycle, 2436 hours after the luteinizing hormone (LH) surges, the dominant follicle releases an ovocyte, in an event called ovulation. After ovulation, the ovocyte only lives for 24 hours or less without fertilization while the remains of the dominant follicle in the ovary become a corpus luteum; this body has a primary function of producing large amounts of progesterone. Under the influence of progesterone, the uterine lining changes to prepare for potential implantation of an embryo to establish a pregnancy. If implantation does not occur within approximately two weeks, the corpus luteum will involute, causing a sharp drop in levels of both progesterone and estrogen. The hormone drop causes the uterus to shed its lining in a process termed menstruation. Menstruation also occurs in closely related primates (apes and monkeys).[11]

The average age of menarche is 1215.[5][12] They may occasionally start as early as eight, and this onset may still be normal.[6] This first period often occurs later in the developing world than the developed world.[8]

The average age of menarche is approximately 12.5 years in the United States,[13] 12.7 in Canada,[14] 12.9 in the UK[15] and 13.1 years in Iceland.[16] Factors such as genetics, diet and overall health can affect timing.[17]

The cessation of menstrual cycles at the end of a woman's reproductive period is termed menopause. The average age of menopause in women is 52 years, with anywhere between 45 and 55 being common. Menopause before age 45 is considered premature in industrialised countries.[18] Like the age of menarche, the age of menopause is largely a result of cultural and biological factors;[19] however, illnesses, certain surgeries, or medical treatments may cause menopause to occur earlier than it might have otherwise.[20]

The length of a woman's menstrual cycle typically varies somewhat, with some shorter cycles and some longer cycles. A woman who experiences variations of less than eight days between her longest cycles and shortest cycles is considered to have regular menstrual cycles. It is unusual for a woman to experience cycle length variations of more than four days. Length variation between eight and 20 days is considered as moderately irregular cycles. Variation of 21 days or more between a woman's shortest and longest cycle lengths is considered very irregular. [21]

The average menstrual cycle lasts 28 days. The variability of menstrual cycle lengths is highest for women under 25 years of age and is lowest, that is, most regular, for ages 25 to 39.[7] Subsequently, the variability increases slightly for women aged 40 to 44.[7]

The luteal phase of the menstrual cycle is about the same length in most individuals (mean 14.13 days, standard deviation 1.41 days)[22] whereas the follicular phase tends to show much more variability (log-normally distributed with 95% of individuals having follicular phases between 10.3 and 16.3 days).[23] The follicular phase also seems to get significantly shorter with age (geometric mean 14.2 days in women aged 1824 vs. 10.4 days in women aged 4044).[23]

Some women with neurological conditions experience increased activity of their conditions at about the same time during each menstrual cycle. For example, drops in estrogen levels have been known to trigger migraines,[24] especially when the woman who suffers migraines is also taking the birth control pill. Many women with epilepsy have more seizures in a pattern linked to the menstrual cycle; this is called "catamenial epilepsy".[25] Different patterns seem to exist (such as seizures coinciding with the time of menstruation, or coinciding with the time of ovulation), and the frequency with which they occur has not been firmly established. Using one particular definition, one group of scientists found that around one-third of women with intractable partial epilepsy has catamenial epilepsy.[25][26][27] An effect of hormones has been proposed, in which progesterone declines and estrogen increases would trigger seizures.[28] Recently, studies have shown that high doses of estrogen can cause or worsen seizures, whereas high doses of progesterone can act like an antiepileptic drug.[29] Studies by medical journals have found that women experiencing menses are 1.68 times more likely to attempt suicide.[30]

Mice have been used as an experimental system to investigate possible mechanisms by which levels of sex steroid hormones might regulate nervous system function. During the part of the mouse estrous cycle when progesterone is highest, the level of nerve-cell GABA receptor subtype delta was high. Since these GABA receptors are inhibitory, nerve cells with more delta receptors are less likely to fire than cells with lower numbers of delta receptors. During the part of the mouse estrous cycle when estrogen levels are higher than progesterone levels, the number of delta receptors decrease, increasing nerve cell activity, in turn increasing anxiety and seizure susceptibility.[31]

Estrogen levels may affect thyroid behavior.[32] For example, during the luteal phase (when estrogen levels are lower), the velocity of blood flow in the thyroid is lower than during the follicular phase (when estrogen levels are higher).[33]

Among women living closely together, it was once thought that the onsets of menstruation tend to synchronize. This effect was first described in 1971, and possibly explained by the action of pheromones in 1998.[34] Subsequent research has called this hypothesis into question.[35]

Research indicates that women have a significantly higher likelihood of anterior cruciate ligament injuries in the pre-ovulatory stage, than post-ovulatory stage.[36]

The most fertile period (the time with the highest likelihood of pregnancy resulting from sexual intercourse) covers the time from some 5 days before until 1 to 2 days after ovulation.[38] In a 28day cycle with a 14day luteal phase, this corresponds to the second and the beginning of the third week. A variety of methods have been developed to help individual women estimate the relatively fertile and the relatively infertile days in the cycle; these systems are called fertility awareness.

There are many fertility testing methods, including urine test kits that detect the LH surge that occurs 24 to 36 hours before ovulation; these are known as ovulation predictor kits (OPKs).[39] Computerized devices that interpret basal body temperatures, urinary test results, or changes in saliva are called fertility monitors. Fertility awareness methods that rely on cycle length records alone are called calendar-based methods.[40] Methods that require observation of one or more of the three primary fertility signs (basal body temperature, cervical mucus, and cervical position)[41] are known as symptoms-based methods.[40]

A woman's fertility is also affected by her age.[42] As a woman's total egg supply is formed in fetal life,[43] to be ovulated decades later, it has been suggested that this long lifetime may make the chromatin of eggs more vulnerable to division problems, breakage, and mutation than the chromatin of sperm, which are produced continuously during a man's reproductive life. However, despite this hypothesis, a similar paternal age effect has also been observed.

As measured on women undergoing in vitro fertilization, a longer menstrual cycle length is associated with higher pregnancy and delivery rates, even after age adjustment.[44]Delivery rates after IVF have been estimated to be almost doubled for women with a menstrual cycle length of more than 34 days compared with women with a menstrual cycle length shorter than 26 days.[44] A longer menstrual cycle length is also significantly associated with better ovarian response to gonadotropin stimulation and embryo quality.[44]

The different phases of the menstrual cycle correlate with women's moods. In some cases, hormones released during the menstrual cycle can cause behavioral changes in females; mild to severe mood changes can occur.[45] The menstrual cycle phase and ovarian hormones may contribute to increased empathy in women. The natural shift of hormone levels during the different phases of the menstrual cycle has been studied in conjunction with test scores. When completing empathy exercises, women in the follicular stage of their menstrual cycle performed better than women in their midluteal phase. A significant correlation between progesterone levels and the ability to accurately recognize emotion was found. Performances on emotion recognition tasks were better when women had lower progesterone levels. Women in the follicular stage showed higher emotion recognition accuracy than their midluteal phase counterparts. Women were found to react more to negative stimuli when in midluteal stage over the women in the follicular stage, perhaps indicating more reactivity to social stress during that menstrual cycle phase.[46] Overall, it has been found that women in the follicular phase demonstrated better performance in tasks that contain empathetic traits.

Fear response in women during two different points in the menstrual cycle has been examined. When estrogen is highest in the preovulatory stage, women are significantly better at identifying expressions of fear than women who were menstruating, which is when estrogen levels are lowest. The women were equally able to identify happy faces, demonstrating that the fear response was a more powerful response. To summarize, menstrual cycle phase and the estrogen levels correlates with womens fear processing.[47]

However, the examination of daily moods in women with measuring ovarian hormones may indicate a less powerful connection. In comparison to levels of stress or physical health, the ovarian hormones had less of an impact on overall mood.[48] This indicates that while changes of ovarian hormones may influence mood, on a day-to-day level it does not influence mood more than other stressors do.

Sexual feelings and behaviors change during the menstrual cycle. Before and during ovulation, high levels of estrogen and androgens result in women having an increased interest in sexual activity.[49] Unlike other animal species, women show interest in sex across all days of the menstrual cycle, regardless of fertility.[50]

Behavior towards potential mating partners changes during different phases of the menstrual cycle.[51][52][53] Near ovulation, women may have increased physical attraction and interest in attending social gatherings with men.[54] During the fertile phase of the cycle, women appear to prefer males who are more masculine.[55] The intensity of mate guarding differs across the phases of the cycle, with increased mate guarding occurring when women are fertile.[53][56][57]

During the fertile phase, many women experience more attraction, fantasies and sexual interest for extra pair men but not for the primary partner.[54][53][58] They also engage in extra-pair flirtations and demonstrate a preference for extra pair copulation.[54][58]

Preferences for voice pitch change across the cycle.[58] When seeking a short term mating partner, women may prefer a male with a low voice pitch, particularly during the fertile phase.[58] During the late follicular phase, it is common for women demonstrate a preference for mates with a masculine, deep voice.[59] Research has also been conducted on the attractiveness of the female voice throughout the cycle.[60] During their most fertile phase of the menstrual cycle, there is some evidence that female voices are rated as significantly more attractive.[60] This effect is not found with women on the birth control pill.[60]

Women's preference for male's body odor can change across the menstrual cycle.[61] Males who score highly on dominance have been rated as sexier by females during the fertile phase of the menstrual cycle. Additionally, during their most fertile phase of the menstrual cycle, women may show preference for the odor of symmetrical men.[53] This effect is not found for women on the birth control pill.[62] Also, during the late follicular and ovulatory phases, women prefer the scent of masculine men.[58] The scent of androsterone (responsible for testosterone levels) is highly preferred by women during the peak of their fertility in the menstrual cycle.[58] Moreover, women may demonstrate preference for men with a scent that indicates developmental stability.[58]

With regard to women's smell across the cycle, some evidence indicates that men use olfactory cues in order to know if a woman is ovulating.[61] Using a rating of women's odors, women who are ovulating have been rated as more attractive by men.[61] Men demonstrate preferences for the scent of fertile women.[61]

Preferences for facial features in mates can also change across the cycle.[58] There has been no difference found in preference for long-term mating partners during the menstrual cycle; however, those seeking a short-term relationship were more likely to choose a partner with more masculine features than usual.[54][59] This was found to be the case especially during the woman's high conception risk stage and when salivary testosterone was high.[63] However, when women are in the luteal (non-fertile) phase, they tend to prefer men (and females) with more feminine faces.[59] A preference is also shown for self-resembling faces and apparent health in faces during the luteal phase of the cycle.[64] Apparent health preferences were found to be strongest when progesterone levels were high.[64] Additionally, during the fertile phase, many women show a preference for men with darker skin pigmentation.[58] Research on facial symmetry is mixed.[65]

Preferences for body features can change during the fertile phase of the cycle. Women seeking a short-term partner demonstrate a preference for taller and muscular males.[58] Women also show preferences of males with masculine bodies at peak fertility.[58][63] Mixed research has been found regarding body symmetry preferences throughout different phases of the cycle.[58]

In short term mates, during the fertile phase, women may show more attraction to dominant men who display social presence.[58] For long-term mates, shifts in desired trait preferences do not occur throughout the cycle.[58]

Females have been found to experience different eating habits at different stages of their menstrual cycle, with food intake being higher during the luteal phase than the follicular phase.[66][67] Food intake increases by approximately 10% during the luteal phase compared to the follicular phase.[67]

Various studies have shown that during the luteal phase woman consume more carbohydrates, proteins and fats and that 24-hour energy expenditure shows increases between 2.5-11.5%.[68] The increasing intake during the luteal phase may be related to higher preferences for sweet and fatty foods, which occurs naturally and is enhanced during the luteal phases of the menstrual cycle.[68] This is due to the higher metabolic demand during this phase.[69] In particular, women tend to show a cravings for chocolate, with higher cravings during the luteal phase.[68]

Females with premenstrual syndrome (PMS) report changes in appetite across the menstrual cycle more than non-sufferers of PMS, possibly due to their oversensitivity to changes in hormone levels.[67] In women with PMS, food intake is higher in the luteal phase than follicular.[70] The remaining symptoms of PMS, including mood changes and physical symptoms, also occur during the luteal phase. No difference for preference of food types has been found between PMS sufferers and non-sufferers.[66]

The different levels of ovarian hormones at different stages of the cycle have been used to explain eating behaviour changes. Progesterone has been shown to promote fat storage, causing a higher intake of fatty foods during the luteal phase when progesterone levels are higher.[67] Additionally, with a high estrogen level dopamine is ineffective in converting to noradrenaline, a hormone which promotes eating, therefore decreasing appetite.[67] In humans, the level of these ovarian hormones during the menstrual cycle have been found to influence binge eating.[71]

It is theorized that the use of birth control pills should affect eating behaviour as they minimise or remove the fluctuations in hormone levels.[66] The neurotransmitter serotonin is also thought to play a role in food intake. Serotonin is responsible for inhibiting eating and controlling meal size,[72] among other things, and is modulated in part by ovarian hormones.[73]

A number of factors affect whether dieting will affect these menstrual processes: age, weight loss and the diet itself. First, younger women are likely to experience menstrual irregularities due to their diet. Second, menstrual abnormalities are more likely with more weight loss. For example, anovulatory cycles can occur as a result of adopting a restricted diet, as well as engaging in a high amount of exercise.[67] Finally, the cycle is affected more by a vegetarian diet compared to a non-vegetarian diet.[74]

Studies investigating effects of the menstrual cycle on alcohol consumption have found mixed evidence.[75] However, some evidence suggests that individuals consume more alcohol during the luteal stage, especially if these individuals are heavy drinkers or have a family history of alcohol abuse.[69]

The level of substance abuse increases with PMS, mostly with addictive substances such as nicotine, tobacco and cocaine.[69] One theory behind this suggests this higher level of substance abuse is due to decreased self-control as a result of the higher metabolic demands during the luteal phase.[69]

Infrequent or irregular ovulation is called oligoovulation.[76] The absence of ovulation is called anovulation. Normal menstrual flow can occur without ovulation preceding it: an anovulatory cycle. In some cycles, follicular development may start but not be completed; nevertheless, estrogens will be formed and stimulate the uterine lining. Anovulatory flow resulting from a very thick endometrium caused by prolonged, continued high estrogen levels is called estrogen breakthrough bleeding. Anovulatory bleeding triggered by a sudden drop in estrogen levels is called withdrawal bleeding.[77] Anovulatory cycles commonly occur before menopause (perimenopause) and in women with polycystic ovary syndrome.[78]

Very little flow (less than 10 ml) is called hypomenorrhea. Regular cycles with intervals of 21 days or fewer are polymenorrhea; frequent but irregular menstruation is known as metrorrhagia. Sudden heavy flows or amounts greater than 80 ml are termed menorrhagia.[79] Heavy menstruation that occurs frequently and irregularly is menometrorrhagia. The term for cycles with intervals exceeding 35 days is oligomenorrhea.[80]Amenorrhea refers to more than three[79] to six[80] months without menses (while not being pregnant) during a woman's reproductive years. The term for painful periods is Dysmenorrhea.

The menstrual cycle can be described by the ovarian or uterine cycle. The ovarian cycle describes changes that occur in the follicles of the ovary whereas the uterine cycle describes changes in the endometrial lining of the uterus. Both cycles can be divided into three phases. The ovarian cycle consists of the follicular phase, ovulation, and the luteal phase, whereas the uterine cycle consists of menstruation, proliferative phase, and secretory phase.[1]

The follicular phase is the first part of the ovarian cycle. During this phase, the ovarian follicles mature and get ready to release an egg.[1] The latter part of this phase overlaps with the proliferative phase of the uterine cycle.

Through the influence of a rise in follicle stimulating hormone (FSH) during the first days of the cycle, a few ovarian follicles are stimulated.[81] These follicles, which were present at birth[81] and have been developing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will stop growing, while one dominant follicle in the ovary will continue to maturity. The follicle that reaches maturity is called a tertiary or Graafian follicle, and it contains the ovum.[81]

Ovulation is the second phase of the ovarian cycle in which a mature egg is released from the ovarian follicles into the oviduct.[82] During the follicular phase, estradiol suppresses release of luteinizing hormone (LH) from the anterior pituitary gland. When the egg has nearly matured, levels of estradiol reach a threshold above which this effect is reversed and estrogen stimulates the production of a large amount of LH. This process, known as the LH surge, starts around day12 of the average cycle and may last 48 hours.[83]

The exact mechanism of these opposite responses of LH levels to estradiol is not well understood.[84] In animals, a gonadotropin-releasing hormone (GnRH) surge has been shown to precede the LH surge, suggesting that estrogen's main effect is on the hypothalamus, which controls GnRH secretion.[84] This may be enabled by the presence of two different estrogen receptors in the hypothalamus: estrogen receptor alpha, which is responsible for the negative feedback estradiol-LH loop, and estrogen receptor beta, which is responsible for the positive estradiol-LH relationship.[85] However, in humans it has been shown that high levels of estradiol can provoke 32 increases in LH, even when GnRH levels and pulse frequencies are held constant,[84] suggesting that estrogen acts directly on the pituitary to provoke the LH surge.

The release of LH matures the egg and weakens the wall of the follicle in the ovary, causing the fully developed follicle to release its secondary oocyte.[81] If it is fertilized by a sperm, the secondary oocyte promptly matures into an ootid and then becomes a mature ovum. If it is not fertilized by a sperm, the secondary oocyte will degenerate. The mature ovum has a diameter of about 0.2mm.[86]

Which of the two ovariesleft or rightovulates appears essentially random; no known left and right co-ordination exists.[87] Occasionally, both ovaries will release an egg;[87] if both eggs are fertilized, the result is fraternal twins.[88]

After being released from the ovary, the egg is swept into the fallopian tube by the fimbria, which is a fringe of tissue at the end of each fallopian tube. After about a day, an unfertilized egg will disintegrate or dissolve in the fallopian tube.[81]

Fertilization by a spermatozoon, when it occurs, usually takes place in the ampulla, the widest section of the fallopian tubes. A fertilized egg immediately begins the process of embryogenesis, or development. The developing embryo takes about three days to reach the uterus and another three days to implant into the endometrium.[81] It has usually reached the blastocyst stage at the time of implantation.

In some women, ovulation features a characteristic pain called mittelschmerz (German term meaning middle pain).[89] The sudden change in hormones at the time of ovulation sometimes also causes light mid-cycle blood flow.[90]

The luteal phase is the final phase of the ovarian cycle and it corresponds to the secretory phase of the uterine cycle. During the luteal phase, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum, which produces progesterone. The increased progesterone in the adrenals starts to induce the production of estrogen. The hormones produced by the corpus luteum also suppress production of the FSH and LH that the corpus luteum needs to maintain itself. Consequently, the level of FSH and LH fall quickly over time, and the corpus luteum subsequently atrophies.[81] Falling levels of progesterone trigger menstruation and the beginning of the next cycle. From the time of ovulation until progesterone withdrawal has caused menstruation to begin, the process typically takes about two weeks, with 14 days considered normal. For an individual woman, the follicular phase often varies in length from cycle to cycle; by contrast, the length of her luteal phase will be fairly consistent from cycle to cycle.[91]

The loss of the corpus luteum is prevented by fertilization of the egg. The syncytiotrophoblast, which is the outer layer of the resulting embryo-containing structure (the blastocyst) and later also becomes the outer layer of the placenta, produces human chorionic gonadotropin (hCG), which is very similar to LH and which preserves the corpus luteum. The corpus luteum can then continue to secrete progesterone to maintain the new pregnancy. Most pregnancy tests look for the presence of hCG.[81]

The uterine cycle has three phases: menses, proliferative, secretory.[92]

Menstruation (also called menstrual bleeding, menses, catamenia or a period) is the first phase of the uterine cycle. The flow of menses normally serves as a sign that a woman has not become pregnant. (However, this cannot be taken as certainty, as a number of factors can cause bleeding during pregnancy; some factors are specific to early pregnancy, and some can cause heavy flow.)[93][94][95]

Eumenorrhea denotes normal, regular menstruation that lasts for a few days (usually 3 to 5 days, but anywhere from 2 to 7 days is considered normal).[89][96] The average blood loss during menstruation is 35 milliliters with 1080 ml considered normal.[97] Women who experience Menorrhagia are more susceptible to iron deficiency than the average person.[98] An enzyme called plasmin inhibits clotting in the menstrual fluid.[99]

Painful cramping in the abdomen, back, or upper thighs is common during the first few days of menstruation. Severe uterine pain during menstruation is known as dysmenorrhea, and it is most common among adolescents and younger women (affecting about 67.2% of adolescent females).[100] When menstruation begins, symptoms of premenstrual syndrome (PMS) such as breast tenderness and irritability generally decrease.[89] Many sanitary products are marketed to women for use during their menstruation.

The proliferative phase is the second phase of the uterine cycle when estrogen causes the lining of the uterus to grow, or proliferate, during this time.[81] As they mature, the ovarian follicles secrete increasing amounts of estradiol, and estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. The estrogen also stimulates crypts in the cervix to produce fertile cervical mucus, which may be noticed by women practicing fertility awareness.[101]

The secretory phase is the final phase of the uterine cycle and it corresponds to the luteal phase of the ovarian cycle. During the secretory phase, the corpus luteum produces progesterone, which plays a vital role in making the endometrium receptive to implantation of the blastocyst and supportive of the early pregnancy, by increasing blood flow and uterine secretions and reducing the contractility of the smooth muscle in the uterus;[102] it also has the side effect of raising the woman's basal body temperature.[103]

While some forms of birth control do not affect the menstrual cycle, hormonal contraceptives work by disrupting it. Progestogen negative feedback decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback on LH release prevent a mid-cycle LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.[104][105][106]

The degree of ovulation suppression in progestogen-only contraceptives depends on the progestogen activity and dose. Low dose progestogen-only contraceptivestraditional progestogen only pills, subdermal implants Norplant and Jadelle, and intrauterine system Mirenainhibit ovulation in about 50% of cycles and rely mainly on other effects, such as thickening of cervical mucus, for their contraceptive effectiveness.[107] Intermediate dose progestogen-only contraceptivesthe progestogen-only pill Cerazette and the subdermal implant Nexplanonallow some follicular development but more consistently inhibit ovulation in 9799% of cycles. The same cervical mucus changes occur as with very low-dose progestogens. High-dose, progestogen-only contraceptivesthe injectables Depo-Provera and Noristeratcompletely inhibit follicular development and ovulation.[107]

Combined hormonal contraceptives include both an estrogen and a progestogen. Estrogen negative feedback on the anterior pituitary greatly decreases the release of FSH, which makes combined hormonal contraceptives more effective at inhibiting follicular development and preventing ovulation. Estrogen also reduces the incidence of irregular breakthrough bleeding.[104][105][106] Several combined hormonal contraceptivesthe pill, NuvaRing, and the contraceptive patchare usually used in a way that causes regular withdrawal bleeding. In a normal cycle, menstruation occurs when estrogen and progesterone levels drop rapidly.[103] Temporarily discontinuing use of combined hormonal contraceptives (a placebo week, not using patch or ring for a week) has a similar effect of causing the uterine lining to shed. If withdrawal bleeding is not desired, combined hormonal contraceptives may be taken continuously, although this increases the risk of breakthrough bleeding.

Breastfeeding causes negative feedback to occur on pulse secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Depending on the strength of the negative feedback, breastfeeding women may experience complete suppression of follicular development, but no ovulation, or normal menstrual cycle may resume.[108] Suppression of ovulation is more likely when suckling occurs more frequently.[109] The production of prolactin in response to suckling is important to maintaining lactational amenorrhea.[110] On average, women who are fully breastfeeding whose infants suckle frequently experience a return of menstruation at fourteen and a half months postpartum. There is a wide range of response among individual breastfeeding women, however, with some experiencing return of menstruation at two months and others remaining amenorrheic for up to 42 months postpartum.[111]

The word "menstruation" is etymologically related to "moon". The terms "menstruation" and "menses" are derived from the Latin mensis (month), which in turn relates to the Greek mene (moon) and to the roots of the English words month and moon.[112]

Even though the average length of the human menstrual cycle is similar to that of the lunar cycle, in modern humans there is no relation between the two.[113] The relationship is believed to be a coincidence.[114][115] Light exposure does not appear to affect the menstrual cycle in humans.[11] A meta-analysis of studies from 1996 showed no correlation between the human menstrual cycle and the lunar cycle[116], nor did data analysed by period-tracking app Clue, submitted by 1.5m women, of 7.5m menstrual cycles[117].

Dogon villagers did not have electric lighting and spent most nights outdoors, talking and sleeping, so they were apparently an ideal population for detecting a lunar influence; none was found.[118]

In a number of countries, mainly in Asia, legislation or corporate practice has introduced formal menstrual leave to provide women with either paid or unpaid leave of absence from their employment while they are menstruating.[119] Countries with policies include Japan, Taiwan, Indonesia, and South Korea.[119] The practice is controversial due to concerns that it bolsters the perception of women as weak, inefficient workers,[119] as well as concerns that it is unfair to men.[120][121]

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