First full genital transplant performed in the USA

30 April 2018 By Georgia Everett Appeared in BioNews 947 A team of surgeons in the USA has successfully performed the first full penis and scrotum transplant on a wounded veteran. The anonymous recipient sustained life-changing injuries while serving in Afghanistan when an improvised explosive device, or IED, caused multiple wounds to his lower pelvis and legs. Eleven surgeons carried out the 14-hour surgery to transplant the entire penis, scrotum and surrounding abdominal wall from a deceased donor. It is the first surgery to transplant such a large and complete part of the genital area. However, the donor’s testes and vas deferens – the tube that carries the semen to the urethra – were not transplanted due to ethical concerns. ‘We would not want to transplant the germline from the donor, because that would mean that, were the recipient to father a child, that actually the genetic background of the child would be from the donor and not from the recipient,’ said Dr Gerald Brandacher, scientific director of the Composite Tissue Allotransplantation Programme at Johns Hopkins Medicine in Baltimore, Maryland, and a surgeon on the case. The recipient will eventually receive a testes prothesis. The operation is hoped to restore urinary and sexual function for the man, said Dr W.P. Andrew Lee, director of plastic and reconstructive surgery at Johns Hopkins. ‘While extremity amputations are visible and resultant disability obvious, some war injuries are hidden and their impact not widely appreciated by others,’ said Dr Lee. ‘Genitourinary injury, where the male service members’ external genitalia are lost or severely damaged, is one such “unspoken injury of war”, [which has] a devastating impact on their identity, self-esteem and intimate relationships.’ The soldier released a statement following the surgery. ‘It’s a real mind-boggling injury to suffer; it is not an easy one to accept,’ he said. ‘When I first woke up, I felt finally more normal… [with] a level of confidence as well. Confidence… like finally I’m OK now.’ Male genital reconstruction procedures are usually performed using tissues from other parts of the body, with a prosthesis implant to enable erection. However, this comes with a higher risk of infection. In addition, with injured veterans there is often insufficient suitable, healthy tissue elsewhere in the body to use for the reconstruction. By performing a full genital transplant, all components can be transplanted including nerves, tendons, bone and blood vessels, allowing almost normal function of the genitalia to be restored. As with other types of transplant, tissue rejection is one risk associated with the procedure, which can be limited by using immunosuppressant drugs. The surgery was funded by The Johns Hopkins Genital Transplant Programme, which focuses on post-traumatic cases, particularly injured soldiers who often have wounds that make conventional options impossible. The transplant team has announced that the university has approved 60 genital transplant surgeries as a part of the...

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Single cell to embryo: unprecedented detail

30 April 2018 By Shaoni Bhattacharya Appeared in BioNews 947 Scientists have unveiled a detailed roadmap of how an embryo forms from a single cell over 24 hours. Three papers published in Science detail the fate of every single cell produced to form an embryo in zebrafish and Xenopus (the western claw-toed frog). ‘Understanding how an organism is made requires knowing which genes are turned on or off as cells make fate decisions, not just the static sequence of a genome,’ said study co-author Dr Sean Megason at Harvard Medical School in Boston, Massachusetts. ‘This is the first technological approach that has allowed us to systematically and quantitatively address this question.’ The scientists used a technique called single-cell RNA sequencing to reveal which genes were being expressed, in which cells, at different times. The researchers profiled more than 200,000 cells at multiple time points for both species over the course of the embryo’s first day. They also developed artificial DNA barcodes to tag each cell and so they could track the material of each cell individually. As an embryo forms, individual cells will commit to becoming different cell types. ‘In one snapshot, we can see the entire story of development unfolding,’ Dr Allon Klein, also at Harvard Medical School, told STAT News. ‘By capturing cells over the first 24 hours of life, we could look at the entire process by which cells were making decisions about the cell types they were going to become.’ A surprise finding was that some cell types emerged much earlier than previously thought. The hope is that better understanding the process of cells differentiating may help in regenerative medicine, with the coaxing of stem cells into different tissue types. ‘With these datasets, if someone wants to make a specific cell type, they now have the recipe for the steps that those cells took as they formed in the embryo,’ said Klein. Klein also told STAT: ‘We could also use it to look at the dynamic of diseases such as developmental disorders...

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1st time rare genetic disorder treated before birth

30 April 2018 By Martha Henriques Appeared in BioNews 947 Three children have been cured of the worst symptoms of a developmental genetic condition with a ‘remarkable’ treatment while still in the womb. Two women – one pregnant with a single child and one with twins – received injections of a protein that their fetuses were unable to produce themselves, due to a condition known as XLHED (X-linked hypohidrotic ectodermal dysplasia). The protein was administered straight into the amniotic fluid around the fetus, according to a study published in the New England Journal of Medicine. The condition is caused by a mutation in a gene involved in developing skin, hair, teeth and nails, carried on the X chromosome. One of the most serious symptoms is having no or very few sweat glands, making it difficult to regulate temperature. XLHED can be fatal if the children become too hot, especially when they are too young to seek out other ways to cool off. GenticDesease Sweat glands develop in a short window between 20 and 30 weeks of pregnancy. Experiments in mice had previously shown that injecting the protein during this phase of development in utero led to offspring that had the glands and could sweat normally. When the same was done for the two women, the children were also born with working glands. The twins’ treatment was particularly successful. As the children grew, their ability to sweat became more and more obvious. At one point, their parents noted that they had completely soaked a car seat with sweat on a hot day. ‘A full rescue of sweating ability – that was so great, just unbelievable,’ Corinna, mother of the twins, told STAT. ‘We were hesitant,’ Professor Holm Schneider, who carried out the study at the University Hospital Erlangen in Germany, told MIT Review. ‘In [Corinna’s] situation you think twice. You think more about the risks involved – three lives – but also the chances that it may bring.’ The third child also developed sweat glands, albeit fewer of them. The child’s mother only received one dose of the protein while pregnant due to limited availability, whereas Corinna – the first to be treated – received three. After an unsuccessful trial of the protein with newborn babies with XLHED, the drug’s maker had closed down and considered it a failure. As a result, only very small amounts of the drug remained left over from the trial. Professor Schneider and his colleagues now hope to develop the drug with a medical charity. As XLHED only affects about 1 in 17,000 people, commercial manufacture of the drug is unlikely ever to be profitable. A few doses of the drug during the crucial developmental window before birth are expected to have life-long effects, although the researchers acknowledge that they will have to wait many decades to confirm this. ‘That’s the remarkable part here, that a genetic disease can be at least partially corrected by a short-term protein treatment,’ said development biologist Dr Marja Mikkola at the University of Helsinki in Finland, who wrote an editorial on the study in the same issue of the journal. ‘This study paves the way for a larger trial of this novel approach.’ The study also opens the door to investigating whether other genetic developmental conditions could be treated in a similar way. ‘There are a number of conditions for which we would seek treatment in utero, but traditionally these have been non-genetic, non-inherited conditions,’ Dr Maisa Feghali at the University of Pittsburgh in Pennsylvania, who was not involved in the study, told STAT. ‘It’s quite a remarkable...

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IVF more successful than ever…

IVF more successful than ever, says major UK report 19 March 2018 By Dr Kimberley Bryon-Dodd Appeared in BioNews 942 Fertility treatment in the UK is more successful and safer than ever before, according to a report from the HFEA (Human Fertilisation and Embryology Authority). IVF is now 85 percent more likely to succeed than when records first began in 1991, said the regulator. Over 20,000 babies were born in 2016 as a result of more than 68,000 IVF treatments, an increase of four percent from 2015. The HFEA’s new report covers fertility treatment trends and success rates for the 2014-2016 period. ‘Assisted reproduction has come a long way in the 40 years since British doctors pioneered IVF with the birth of Louise Brown,’ said Sally Cheshire, chair of the HFEA. ‘With well over a million treatments performed in the UK since records began, and more than 300,000 babies born, as a country we remain at the forefront of fertility treatment.’ She added that the report was ‘the most extensive we’ve ever produced’. The report found that the average birth rate for women of all ages undergoing fertility treatment was 21 percent, with this increasing to 29 percent for women under 35. A total of 42 percent of all women undergoing IVF treatment in 2016 were under 35. Births from fertility treatments are also safer, said the report, with far fewer multiple births than ever before. This has fallen from around one in every four, or 28 percent, of IVF births in 2008 to 11 percent in 2016. The report also noted that fertility treatment ‘has become available to a wider range of people’. While the majority of patients receiving IVF treatment in 2016 were heterosexual couples (95.3 percent), since 2014 there has been a 30 percent increase in the number of IVF treatments for patients with a female partner (to 2.5 percent), and a 35 percent increase in the number of treatments with no partner (1.9 percent). The report also noted that treatments involving donor eggs and sperm are increasing in popularity, as is the use of frozen eggs in IVF. For the first time ever, the report also details the number of surrogacy treatments in 2016. There were 232 surrogate cycles and 79 births in 2016. ‘We welcome the fact that the HFEA has, for the first time, included data on surrogacy in its report,’ said Sarah Norcross, Director of the Progress Educational Trust (which publishes BioNews). ‘At a time when Parliament is working to permit surrogacy for single people and when the Law Commission is reviewing surrogacy law more broadly, it is increasingly important to have access to reliable data about this...

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Snuggled babies show lasting changes in DNA

04 December 2017 By Sam Sherratt Appeared in BioNews 929   Close, physical contact – or the lack of it – at an early age may lead to lasting changes to the genes, suggest researchers. The team at the University of British Columbia in Vancouver, Canada, showed that babies receiving less physical contact during times of emotional distress developed a significantly altered epigenome compared with children receiving lots of contact. Their epigenomes were also under-developed by comparison. ‘In children, we think slower epigenetic ageing could reflect less favourable developmental progress,’ said Professor Michael Kobor, senior author on the study published in Development and Psychopathology. The epigenome refers to the semi-permanent chemical changes or ‘marks’ added on to human DNA that can act as on/off switches for genes. The team asked the parents of 94 five-week-old babies to keep daily diaries recording physical contact with their child and their infants’ behaviours, such as sleeping and crying, during the duration of the study. DNA swabs were taken from the children four to five years later. The researchers looked at a specific epigenetic change called DNA methylation. They found consistent differences in the methylation pattern between children who received a lot of contact, to those receiving less contact, at five DNA sites. Of these, two sites were within genes: one involved in metabolism and the other in the immune system. The researchers were concerned by an additional finding: as people age their epigenomes alter according to a predictable pattern as genes are turned on and off during development. But the children who showed higher levels of emotional distress and received less physical affection had a younger ‘epigenetic age’ than they should have had. ‘We plan to follow up on whether the “biological immaturity” we saw in these children carries broad implications for their health, especially their psychological development,’ said lead author Dr Sarah Moore. ‘If further research confirms this initial finding, it will underscore the importance of providing physical contact, especially for distressed infants.’ A second study published last week in JAMA Psychiatry also suggested that early emotional experiences may impact across generations. It found that the daughters of Finnish women who were evacuated to foster homes in Sweden during World War II as children were twice as likely to be hospitalised for a psychiatric disorder than their female cousins whose mothers were not evacuated. No effect was seen for boys. The study used the Finnish National Archives to identify and study over 93,000 children of war evacuees. Lead author Dr Torsten Santavirta, at Uppsala University in Sweden, told the New York Times that it was possible that trauma cause changes in gene expression that are then inherited, but that the team did not have access to genetic information in this...

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Fertility: Vitamin D may influence success rate

Published Saturday 18 November 2017 By Tim Newman Fact checked by Jasmin Collier www.medicalnewstoday.com A new meta-analysis has concluded that there is a relationship between a woman’s vitamin D status and the success rate of assisted reproduction therapy. Infertility is a common and distressing issue, and it affects an estimated 6.1 million couples in the United States. That’s around 10 percent of all couples of childbearing age. Over the years, assisted reproduction therapy (ART) — including in vitro fertilization (IVF) and fertility medication — has become much more widespread and its success rates have increased. As an example, depending on the woman’s age and the clinic involved, success rates of IVF in the U.S. range from 13–43 percent. An initial uptick in ART success rates was thanks to improved methods of picking out embryos with the highest chances of survival. But more recently, success rates have started to stagnate. Vitamin D and reproduction Researchers believe that there is room for improvement in ART success rates. A range of potential factors are being explored, and some scientists have turned their attention to the potential role of vitamin D. The vast majority of our vitamin D supply is generated in our skin after exposure to sunlight. This means that individuals who live in colder or darker environments are more susceptible to lower vitamin D levels, as are people with darker skin, those who regularly wear clothes covering the majority of their skin, and those who rarely go outside. A link between vitamin D and fertility has been theorized based on a number of observations. For instance, vitamin D receptors and enzymes have been found in the endometrium. Also, in animal studies, vitamin D deficiency causes poorer fertility and reduced function of the reproductive organs. In humans, vitamin D deficiency has been shown to increase the risk of preeclampsia, pregnancy-induced hypertension, gestational diabetes, and lower birth weight. Researchers from the University of Birmingham and Birmingham Women’s and Children’s National Health Service (NHS) Foundation Trust, both in the United Kingdom, decided to take a look at existing data to probe the links further. They carried out a meta-analysis, reopening 11 studies including 2,700 women undergoing ART. Their findings are published this week in the journal Human Reproduction. Vitamin D deficiency and lower success rates The featured studies involved women undergoing IVF or intracytoplasmic sperm injection, frozen embryo transfer, or both. All the participants’ vitamin D levels were checked by blood test. Vitamin D concentrations of more than 75 nanomoles per liter of blood were considered as sufficient, under 75 nanomoles per liter of blood as insufficient, and under 50 nanomoles per liter of blood as deficient. The analysis showed that procedures in women with adequate vitamin D levels were one third more likely to lead to live births than in women who were deficient. When the researchers looked at positive pregnancy tests and clinical pregnancies — that is, where a heartbeat can be detected — rather than live births, the results were similar. When compared with women who had insufficient vitamin D concentrations, those with sufficient amounts were 46 percent more likely to have a clinical pregnancy, and 34 percent more likely to have a positive pregnancy test result. The analysis showed no associations between miscarriage and vitamin D concentrations. “One startling finding was the high prevalence of vitamin D deficiency among these women. We found that only 26 percent of women in the studies had sufficient concentrations of vitamin D; 35 percent had deficient concentrations, and 45 percent had insufficient concentrations.” The researchers are quick to explain the study’s limitations. Team leader Dr. Justin Chu says, “Although an association has been identified, the beneficial effect of correction of vitamin D deficiency or...

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