News List
First baby born via uterus transplant from a deceased donor

Currently, uterus donation is only available for women with family members who are willing to donate. With live donors in short supply, the new technique might help to increase availability and give more women the option of pregnancy. The first baby has been born following a uterus transplantation from a deceased donor, according to a case study from Brazil published in The Lancet. The study is also the first uterine transplantation in Latin America.
The new findings demonstrate that uterus transplants from deceased donors are feasible and may open access for all women with uterine infertility, without the need for live donors. However, the outcomes and effects of donations from live and deceased donors are yet to be compared, and the surgical and immunosuppression techniques will be optimised in the future.
The recipient of the transplant was a patient with uterine infertility. Previously, there have been 10 other uterus transplants from deceased donors attempted in the USA, Czech Republic and Turkey, but this is the first to result in a livebirth. The first childbirth following uterine transplantation from living donors occurred in Sweden in September 2013 and were also published in The Lancet. In total, there have been 39 procedures of this kind, resulting in 11 livebirths so far (see Comment Appendix).
Infertility affects 10-15% of couples of reproductive age. Of this group, one in 500 women have uterine anomalies due to congenital anomalies, or through unexpected malformation, hysterectomy, or infection. Before the advent of uterus transplants, the only available options to have a child were adoption or surrogacy.
The use of deceased donors could greatly broaden access to this treatment, and our results provide proof-of-concept for a new option for women with uterine infertility. says Dr Dani Ejzenberg, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, who led the research. The first uterus transplants from live donors were a medical milestone, creating the possibility of childbirth for many infertile women with access to suitable donors and the needed medical facilities. However, the need for a live donor is a major limitation as donors are rare, typically being willing and eligible family members or close friends. The numbers of people willing and committed to donate organs upon their own deaths are far larger than those of live donors, offering a much wider potential donor population.
The surgery took place in September 2016. The recipient of the uterus was a 32 year-old woman born without a uterus as a result of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. She had one in-vitro fertilisation (IVF) cycle four months before transplant, resulting in eight fertilised eggs which were cryopreserved.
The donor was 45 years old and died of subarachnoid haemorrhage (a type of stroke involving bleeding on the surface of the brain).
The uterus was removed from the donor and then transplanted into the recipient in surgery lasting 10.5 hours. The surgery involved connecting the donor uterus and recipients veins and arteries, ligaments, and vaginal canals.
After surgery, the recipient stayed in intensive care for two days, then spent six days on a specialised transplant ward. She received five immunosuppression drugs, as well as antimicrobials, anti-blood clotting treatment and aspirin while in hospital. Immunosuppression was continued outside of hospital until the birth.
Five months after transplantation, the uterus showed no signs of rejection, ultrasound scans showed no anomalies, and the recipient was having regular menstruation.
The fertilised eggs were implanted after seven months. The authors note that they were able to implant the fertilised eggs into the transplant uterus much earlier than previous uterus transplants (where this typically occurred after one year). Implantation was planned to be at six months, but the endometrium was not thick enough at this stage, so it was postponed for one month.
Ten days after implantation, the recipient was confirmed to be pregnant. Non-invasive prenatal testing was done at 10 weeks, showing a normal fetus, and ultrasound scans at 12 and 20 weeks revealed no fetal anomalies.
There were no issues during the recipients pregnancy, other than a kidney infection at 32 weeks which was treated with antibiotics in hospital.
The baby girl was born via caesarean section at 35 weeks and three days, and weighed 2550g (around 6lbs). The transplanted uterus was removed during the caesarean section and showed no anomalies.
Both the recipient and baby were discharged three days after birth, with an uneventful early follow-up. The immunosuppressive therapy was suspended at the end of the hysterectomy. At the age of seven months and 20 days (when the manuscript was written), the baby continued to breastfeed and weighed 7.2kg (15lbs and 14oz).
The authors note that transplants from deceased donors might have some benefits over donations from live donors, including removing surgical risks for a live donor, and that many countries already have well-established national systems to regulate and distribute organ donations from deceased donors. In addition, through implanting the fertilised eggs sooner they reduced the amount of time taking immunosuppression drugs, which could help to reduce side effects and costs.
The authors note that the transplant involved major surgery and recipients for uterus transplants would need to be healthy to avoid complications during or after this. They also note that the surgery used high doses of immunosuppression, which could be reduced in future. It also involved moderate levels of blood loss, although these were manageable.
The recipient and her partner received monthly psychological counselling from professionals specialised in transplants and fertility throughout before, during and after the transplant.
Writing in a linked Comment, Dr Antonio Pellicer, IVI-Roma, Italy, notes that while the procedure is a breakthrough, it is still in the early stages of refining and many questions are still unsolved. He says: All in all, the research to be done in this field (whether from alive or deceased donors) should maximise the livebirth rate, minimise the risks for the patients involved in the procedures (donor, recipient, and unborn child), and increase the availability of organs. With the expansion of the field, the number of procedures will increase, and this will allow the community to set different types of study designs, such as comparison studies (ideally randomised) or long prospective series. In an expanding field such as uterus transplantation, the role of collaborative networks and societies such as the International Society of Uterus Transplantation or new interest groups in already existing scientific societies will be crucial. They should promote education and guidance so that the groups performing uterus transplantation for the first time can benefit from the experience of the pioneers. They should also encourage forthcoming procedures to be done and reported in a transparent way by endorsing prospective registration of the procedures and by developing accurate registries.
This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil. It was conducted by researchers from Hospital das Clínicas, University of São Paulo School of Medicine.

Playing high school football changes the teenage brain

Magnetic resonance imaging (MRI) brain scans have revealed that playing a single season of high school football can cause microscopic changes in the grey matter in young players brains. These changes are located in the front and rear of the brain, where impacts are most likely to occur, as well as deep inside the brain.
Credit: Nan-Jie Gong and Chunlei Liu, UC Berkeley
A single season of high school football may be enough to cause microscopic changes in the structure of the brain, according to a new study by researchers at the University of California, Berkeley, Duke University and the University of North Carolina at Chapel Hill.
The researchers used a new type of magnetic resonance imaging (MRI) to take brain scans of 16 high school players, ages 15 to 17, before and after a season of football. They found significant changes in the structure of the grey matter in the front and rear of the brain, where impacts are most likely to occur, as well as changes to structures deep inside the brain. All participants wore helmets, and none received head impacts severe enough to constitute a concussion.
The study, which is the cover story of the November issue of Neurobiology of Disease, is one of the first to look at how impact sports affect the brains of children at this critical age. This study was made available online in July 2018 ahead of final publication in print this month.
It is becoming pretty clear that repetitive impacts to the head, even over a short period of time, can cause changes in the brain, said study senior author Chunlei Liu, a professor of electrical engineering and computer sciences and a member of the Helen Wills Neuroscience Institute at UC Berkeley. This is the period when the brain is still developing, when it is not mature yet, so there are many critical biological processes going on, and it is unknown how these changes that we observe can affect how the brain matures and develops.
Concerning trends
One bonk to the head may be nothing to sweat over. But mounting evidence shows that repeated blows to the cranium -- such as those racked up while playing sports like hockey or football, or through blast injuries in military combat -- may lead to long-term cognitive decline and increased risk of neurological disorders, even when the blows do not cause concussion.
Over the past decade, researchers have found that an alarming number of retired soldiers and college and professional football players show signs of a newly identified neurodegenerative disease called chronic traumatic encephalopathy (CTE), which is characterized by a buildup of pathogenic tau protein in the brain. Though still not well understood, CTE is believed to cause mood disorders, cognitive decline and eventually motor impairment as a patient ages. Definitive diagnosis of CTE can only be made by examining the brain for tau protein during an autopsy.
These findings have raised concern over whether repeated hits to the head can cause brain damage in youth or high school players, and whether it is possible to detect these changes at an early age.
There is a lot of emerging evidence that just playing impact sports actually changes the brain, and you can see these changes at the molecular level in the accumulations of different pathogenic proteins associated with neurodegenerative diseases like Parkinsons and dementia, Liu said. We wanted to know when this actually happens -- how early does this occur?
A matter of grey and white
The brain is built of white matter, long neural wires that pass messages back and forth between different brain regions, and grey matter, tight nets of neurons that give the brain its characteristic wrinkles. Recent MRI studies have shown that playing a season or two of high school football can weaken white matter, which is mostly found nestled in the interior of the brain. Liu and his team wanted to know if repetitive blows to the head could also affect the brain s gray matter.
Grey matter in the cortex area is located on the outside of the brain, so we would expect this area to be more directly connected to the impact itself, Liu said.
The researchers used a new type of MRI called diffusion kurtosis imaging to examine the intricate neural tangles that make up gray matter. They found that the organization of the gray matter in players brains changed after a season of football, and these changes correlated with the number and position of head impacts measured by accelerometers mounted inside players helmets.
The changes were concentrated in the front and rear of the cerebral cortex, which is responsible for higher-order functions like memory, attention and cognition, and in the centrally located thalamus and putamen, which relay sensory information and coordinate movement.
Although our study did not look into the consequences of the observed changes, there is emerging evidence suggesting that such changes would be harmful over the long term, Liu said.
Tests revealed that students cognitive function did not change over the course of the season, and it is yet unclear whether these changes in the brain are permanent, the researchers say.
The brain microstructure of younger players is still rapidly developing, and that may counteract the alterations caused by repetitive head impacts,said first author Nan-Ji Gong, a postdoctoral researcher in the Department of Electrical Engineering and Computer Sciences at UC Berkeley.
However, the researchers still urge caution -- and frequent cognitive and brain monitoring -- for youth and high schoolers engaged in impact sports.
I think it would be reasonable to debate at what age it would be most critical for the brain to endure these sorts of consequences, especially given the popularity of youth football and other sports that cause impact to the brain, Liu said.

A new approach to detecting cancer earlier from blood tests

Cancer scientists led by principal investigator Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have combined liquid biopsy, epigenetic alterations and machine learning to develop a blood test to detect and classify cancer at its earliest stages.
The findings, published online today in Nature, describe not only a way to detect cancer, but hold promise of being able to find it earlier when it is more easily treated and long before symptoms ever appear, says Dr. De Carvalho, Senior Scientist at the cancer centre, University Health Network.
We are very excited at this stage, says Dr. De Carvalho. A major problem in cancer is how to detect it early. It has been a needle in the haystack problem of how to find that one-in-a-billion cancer-specific mutation in the blood, especially at earlier stages, where the amount of tumour DNA in the blood is minimal.
By profiling epigenetic alterations instead of mutations, the team was able to identify thousands of modifications unique to each cancer type. Then, using a big data approach, they applied machine learning to create classifiers able to identify the presence of cancer-derived DNA within blood samples and to determine what cancer type. This basically turns the one needle in the haystack problem into a more solvable thousands of needles in the haystack, where the computer just needs to find a few needles to define which haystack has needles.
The scientists tracked the cancer origin and type by comparing 300 patient tumour samples from seven disease sites (lung, pancreatic, colorectal, breast, leukemia, bladder and kidney) and samples from healthy donors with the analysis of cell-free DNA circulating in the blood plasma. In every sample, the floating plasma DNA matched the tumour DNA. The team has since expanded the research and has now profiled and successfully matched more than 700 tumour and blood samples from more cancer types.
Beyond the lab, next steps to further validate this approach include analysing data from large population health research studies already under way in several countries, where blood samples were collected months to years before cancer diagnosis. Then the approach will need to be ultimately validated in prospective studies for cancer screening.
Dr. De Carvalho is a trained immunologist (University of Sao Paulo, Brazil) with postdoctoral training in cancer epigenomics (University of Southern California, USA) whose research focuses on cancer epigenetics. He holds the Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy and is an Associate Professor in Cancer Epigenetics, Department of Medical Biophysics, University of Toronto.
The research was supported by University of Toronto s McLaughlin Centre, Canadian Institutes of Health Research, Canadian Cancer Society, Ontario Institute for Cancer Research through the Province of Ontario, and The Princess Margaret Cancer Foundation.
Story Source:
Materials provided by University Health Network. Note: Content may be edited for style and length.
Journal Reference:
Shu Yi Shen, Rajat Singhania, Gordon Fehringer, Ankur Chakravarthy, Michael H. A. Roehrl, Dianne Chadwick, Philip C. Zuzarte, Ayelet Borgida, Ting Ting Wang, Tiantian Li, Olena Kis, Zhen Zhao, Anna Spreafico, Tiago da Silva Medina, Yadon Wang, David Roulois, Ilias Ettayebi, Zhuo Chen, Signy Chow, Tracy Murphy, Andrea Arruda, Grainne M. O’Kane, Jessica Liu, Mark Mansour, John D. McPherson, Catherine O’Brien, Natasha Leighl, Philippe L. Bedard, Neil Fleshner, Geoffrey Liu, Mark D. Minden, Steven Gallinger, Anna Goldenberg, Trevor J. Pugh, Michael M. Hoffman, Scott V. Bratman, Rayjean J. Hung, Daniel D. De Carvalho. Sensitive tumour detection and classification using plasma

Degenerating hair cells in the inner ear can be made to function again, suggests a new report.

There are more than 300 genetic defects that have been found to prevent the hair cells in the human inner ear  the sensory cells of the ear as it were, from working properly. This can result in severe hearing impairment and even to complete hearing loss. Together with researchers at the Medical School in Harvard, Boston, Lukas Landegger of MedUni Vienna s Department of Ear, Nose and Throat Diseases has now succeeded, for the very first time, to repair this defect in an animal model -- by using a modified, non-pathogenic adeno-associated virus (Anc80L65), which is introduced into the ear by way of a Trojan Horse to deliver genes to restore the functionality of the damaged hair cells.
The study has been published in the leading journal Nature Biotechnology. Lukas Landegger is doing his PhD at MedUni Vienna and is currently working at Harvard as part of his course.
At the moment, ENT experts are able to use cochlea implants as a technical solution for restoring the hearing of people with congenital hearing loss. The Medical University of Vienna has been a global leader in the development and use of cochlear implants since 1977, when the world s first multichannel cochlear implant was implanted in Vienna. However, these electronic implants with their twelve electrodes cannot 100% replace the more than 3,000 hair cells in the inner ear, which give as much finer hearing, says Wolfgang Gstöttner, Head of the ENT Department at MedUni Vienna.
Adeno-associated virus as a gene vector
The commonest form of congenital deafness in children is due to the genetic mutation of GJB2 and GJB6. This mutation prevents the protein connexin 26, which is responsible for the cells in the cell complex of the inner ear, from working properly. As a result, the small hairs in the cochlea do not form properly or do not function properly. However, so far no-one has successfully managed to introduce the repair genes into the hair cells to start them working again. The basis for correcting this and many other mutations has now been created in an animal model with the non-pathogenic adeno-associated virus (AAV) replicated in the laboratory. This virus is infiltrated into the hair cells as a gene vector (carrier). What was surprising was that, in addition to the inner hair cells that are responsible for signal transduction, it was also possible to treat the 90% of outer hair cells, which perform an important amplification function in the inner ear and have hitherto been virtually inaccessible for gene therapy. This adeno-associated virus has already been used for restoring liver cells and in the retina.
Once the functionality of the virus had been initially proven in the treatment of a mouse model for Usher syndrome, which is the commonest cause of deafblindness worldwide (Pan et al. Nat Biotechnol 2017), further studies are required to determine the tolerability of the vector, so that this approach will soon be available for treating newborn babies with congenital hearing loss.

Scientists are developing a new approach to restore the hearing loss.

Researchers have taken an important step toward what may become a new approach to restore the hearing loss. In a new study, out today in the European Journal of Neuroscience, scientists have been able to regrow the sensory hair cells found in the cochlea -- a part of the inner ear -- that converts sound vibrations into electrical signals and can be permanently lost due to age or noise damage.
Hearing impairment has long been accepted as a fact of life for the aging population -- an estimated 30 million Americans suffer from some degree of hearing loss. However, scientists have long observed that other animals -- namely birds, frogs, and fish -- have been shown to have the ability to regenerate lost sensory hair cells.
It s funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration, said Jingyuan Zhang, Ph.D., with the University of Rochester Department of Biology and a co-author of the study. We re the only vertebrates that can t do it.
Research conducted in the lab of Patricia White, Ph.D., in 2012 identified a family of receptors -- called epidermal growth factor (EGF) -- responsible for activating support cells in the auditory organs of birds. When triggered, these cells proliferate and foster the generation of new sensory hair cells. She speculated that this signaling pathway could potentially be manipulated to produce a similar result in mammals. White is a research associate professor in the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience and lead author of the current study.
In mice, the cochlea expresses EGF receptors throughout the animal s life, but they apparently never drive regeneration of hair cells, said White. Perhaps during mammalian evolution, there have been changes in the expression of intracellular regulators of EGF receptor family signaling. Those regulators could have altered the outcome of signaling, blocking regeneration. Our research is focused on finding a way switch the pathway temporarily, in order to promote both regeneration of hair cells and their integration with nerve cells, both of which are critical for hearing.
In the new study, which involved researchers from URMC and the Massachusetts Ear and Eye Infirmary, which is part of Harvard Medical School, the team tested the theory that signaling from the EGF family of receptors could play a role in cochlear regeneration in mammals. The researchers focused on a specific receptor called ERBB2 which is found in cochlear support cells.
The researchers investigated a number of different methods to activate the EGF signaling pathway. One set of experiments involved using a virus to target ERBB2 receptors. Another, involved mice genetically modified to overexpress an activated ERBB2. A third experiment involved testing two drugs, originally developed to stimulate stem cell activity in the eyes and pancreas, that are known activate ERBB2 signaling.
The researchers found that activating the ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to proliferate and start the process of activating other neighboring stem cells to become new sensory hair cells. Furthermore, it appears that this process not only could impact the regeneration of sensory hair cells, but also support their integration with nerve cells.
The process of repairing hearing is a complex problem and requires a series of cellular events, said White. You have to regenerate sensory hair cells and these cells have to function properly and connect with the necessary network of neurons. This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing

Drinking water lowers the risk of bladder infections

Bladder infections are extremely common among women. New research, however, shows that boosting water intake might reduce these infections by almost half.
a woman drinking water
Drinking plenty of water can help keep UTIs at bay.
A urinary tract infection (UTI) can affect any part of the urinary tract, including the urethra, bladder, ureters, or kidneys.
A bladder infection is the most common type of UTI.
Approximately half of all women will experience a UTI in their lifetime.
For those who experience this type of infection once, a solid 25 percent can expect to have another later on in life.
Women are likelier to develop a bladder infection than men due to differing anatomy — the female urethra is shorter than that of men, which means that bacteria can reach the bladder more easily.
Also, the urethra opening is closer to the rectum in women, and the rectum houses lots of bacteria. These bacteria are most commonly associated with UTIs.
Bladder infections, when caught early, don t usually cause serious complications, and they are easily treated with antibiotics.
If not treated, however, they can lead to kidney infections. Symptoms of bladder infections include a burning feeling while passing urine and frequent or intense urges to go to the bathroom, even if there is not a lot of urine to pass.
The new research, which was led by senior study author Dr. Yair Lotan, from the Simmons Cancer Center at the University of Texas Southwestern in Dallas, is now published in the journal JAMA Internal Medicine.

Existing drug shows promise for treating aggressive breast cancer

An existing antipsychotic drug could become the first targeted treatment for an aggressive type of breast cancer that is hard to treat.
Antipsychotic needle
An existing drug may help in the fight against breast cancer.
A study led by the University of Bradford in the United Kingdom reveals that the drug pimozide can reduce cancer cell numbers, growth, and spread in triple-negative breast cancer.
In a paper that is to feature in the journal Oncotarget, the researchers describe how they used laboratory cells and mice implanted with tumors to demonstrate the drug s effect.
Some of the tests they carried out also suggest that pimozide could be effective against non-small cell lung cancer, which is the most common form of lung cancer.
Following this success, the team has applied for a patent and intends to start clinical trials in humans as soon as funds permit.

Antibiotic may prevent breast cancer recurrence

One of cancer researchers top priorities is discovering ways to reduce the risk that cancer will recur or metastasize. A recent, small-scale study may have found a common, cost-effective drug that does just that.
Breast cancer cell
An antibiotic might help prevent breast cancer from coming back.
Cancer stem cells (CSCs), also known as tumor-initiating cells, are a hot topic among researchers.
These cells are resistant to current treatments and play a significant role in both metastasis and recurrence, which are two of the biggest challenges in cancer treatment.
Because of this, finding successful ways of clearing up CSCs is of great interest.
Researchers from the University of Salford in the United Kingdom may have uncovered a treatment that could play an important role.
These scientists spend their time testing drugs that the Food and Drug Administration (FDA) have already approved. They investigate whether any existing medicines might also be able to help in the fight against cancer.
Concentrating on drugs in this way means that if they do find an existing drug that works against cancer, it could potentially reach the clinic faster.
In a recent paper now published in the journal Frontiers in Oncology, the scientists outline the potential use of an antibiotic called doxycycline to clear up CSCs.

How can gold help repair muscle injuries?

Researchers have revealed that nanoparticles of gold, attached to natural anti-inflammatory agents, work well on inflammation and can also promote muscle regeneration.
a man with knee pain
Scientists now believe that we can use gold to help treat muscle injuries.
Muscle injuries can take a while to recover from. This is because inflammation that occurs soon after an injury can hang on for some time.
That inflammation might also be very easy to re-aggravate.
However, there may be some good news on the horizon for those with muscle strains or tears.
Scientists have now designed a way to combine a natural anti-inflammatory agent with tiny bits of gold.
They recently published the new findings in the Proceedings of the National Academy of Sciences.
Reducing inflammation
It has been known for some time that injections of an anti-inflammatory cytokine called interleukin 4 (IL-4) into an injured muscle can help that muscle recover faster.
There is a caveat, however; the substance breaks down quickly and requires multiple applications that can result in unwelcome side effects. The solution to this problem might (literally) be golden.