Body

Amsterdam, NL, November 15, 2019 - Constipation is a common complaint in patients with Parkinson's disease (PD). Fecal microbiome transplantation (FMT) and pre- and probiotics are potential options for treating constipation and restoring the microbiome of patients with Parkinson's disease (PD), but scientists warn that clinical data are scarce, and more research is needed before supporting their use. They present their findings in a review article in the Journal of Parkinson's Disease.

In this review, investigators evaluate the current state of knowledge about the potential for using FMT and pre- and probiotics to restore the normal microbial balance of the gut in PD patients and highlight the questions that still need to be answered.

FMT consists of transferring liquid filtrate feces from a healthy screened individual to a patient via nasogastric or nasoduodenal tube, enema, or colonoscope. "FMT is an interesting option for restoring the changes in the microbiome of PD patients," explained lead investigator Teus van Laar, MD, PhD, Director of the Parkinson Expertise Center Groningen, Department of Neurology, University Medical Center Groningen, University of Groningen, The Netherlands. "It is an attractive technique because the administration is relatively simple and in general it has only a mild pattern of adverse effects. However, no rigorous clinical trials have been performed yet, which leaves multiple questions open about the presumed optimal content of FMT, the route of administration, the volume of FMT and the long-term effects."

Administration of Lactobacillus and Bifidobacterium over a period of 4-12 weeks has repeatedly proven to be effective in treating constipation in PD. However, no solid clinical data are available about the possible effects of these probiotic treatments on motor symptoms or progression of PD. Following promising results of prebiotics in animal studies, the first clinical trial on the use of FMT in PD patients is now underway at the University of Ghent (Belgium) and is scheduled to be completed by the end of 2019. With target recruitment of 40 PD patients and follow-up intervals of three months for up to one year, the trial will assess the development of PD symptoms. Investigators noted that the trial's inclusion criteria did not include or exclude constipation, which may complicate the interpretation of results.

The investigators recommend that FMT treatments in patients with PD should wait until better clinical data become available in order to select the right target populations and have good estimates of anticipated clinical effects. They highlight several knowledge gaps that need to be addressed first:

FMT has not yet proven to be effective on motor symptoms or progression of PD

Which route of administration of FMT is optimal

Optimal donor content and frequency of FMT in PD

Probiotics in PD have so far only been shown to have an effect on constipation

Prebiotics have only been shown to have an effect in animal models and have not yet been tested in clinical trials

Possible adverse effects and possible contra-indications of FMT are still unknown

"FMT is a black box with too many unanswered questions at the moment, also with respect to safety concerns," concluded Prof. van Laar. "FMT or the use of pro- and prebiotics might become standard treatments in selected subgroups of PD patients in the future, but there are no good data yet in the public domain to support their use in PD patients. We hope this review will activate colleagues to start proper research on this topic as soon as possible, rather than to begin therapy without conclusive clinical data."

PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. Although the jury is still out, research has shown that it may actually begin in the enteric nervous system, the part of the autonomic nervous system that controls the gastrointestinal organs.

(Boston)--Computational modeling is the use of computers to simulate and study the behavior of complex systems. Computational approaches are widely adopted in the bioimedical sciences and can be used to sift through large volumes of complex data to extract recurrent patterns that may point to a disease's causes and effects.

Researchers from Boston University School of Medicine (BUSM) have developed a novel computational method, integration of Epi-DNA and Gene Expression (iEDGE), whose application to the analysis of more than 8,500 tumor profiles from The Cancer Genome Atlas has led to the discovery of genes whose alteration (mutation or copy number alteration) may contribute to cancer susceptibility. This breakthrough may lead to new therapeutic targets for numerous cancers.

According to the researchers, iEDGE identified several candidate breast cancer drivers, including RBM17 (a splicing factor amplified in Triple-Negative Breast Cancer) and SIRT3 (a candidate tumor suppressor and a promising therapeutic target). It also identified multiple candidate pan-cancer drivers, including TRIP13 (previously shown to promote tumor growth in colorectal cancer and a predictor of poor prognosis in prostate cancer), ORAOV1 (a gene overexpressed in many solid tumors), and TPX2 (a potent oncogene amplified in many cancers and a promising therapeutic target), among others.

"While further functional studies will be needed to evaluate the therapeutic relevance of our findings, these results study show the efficacy of iEDGE at identifying candidate drivers and potentially novel targets for therapy," explained corresponding author Stefano Monti, PhD, associate professor of medicine at BUSM.

The open source tool iEDGE is freely downloadable at github.com/montilab/iEDGE and biomedical scientists are able to apply it to the analysis of their own data to advance their research. As a companion to the published findings, a web-based portal for the interactive querying and visualization of the study's results is hosted at montilab.bu.edu/iEDGE

"Through the web-based portal, all the data and results of our pan-cancer analysis are accessible to the research community, who can search for gene candidates and for their potential mechanisms of action, and thus support their translational research toward more effective cancer treatments," added first author Amy Li, PhD, a graduate from the Boston University Bioinformatics PhD program.

BOSTON - Adolescents and young adults who were born to mothers with HIV but remained uninfected themselves still face a greatly heightened risk of obesity and asthma-like symptoms, researchers from Massachusetts General Hospital (MGH) have found. In a study published in Journal of Acquired Immune Deficiency Syndromes (JAIDS), the team revealed for the first time that HIV-negative teens and young adults with a history of in utero HIV exposure showed more than fourfold increased odds of obesity and asthma-like symptoms compared to their unexposed peers.

"Our study found that there are metabolic and immune consequences to being exposed to HIV in utero," says Lindsay Fourman, MD, of the Metabolism Unit, Department of Medicine, MGH, and lead author of the study. "These results underscore the need for all children of mothers with HIV - even those who are HIV-negative - to be screened and continually monitored over their lifetimes by clinicians attuned to their health risks. Too often, their exposure to HIV is lost from their medical records after they are found to be HIV-negative."

Globally, more than one million babies are born each year to mothers with HIV. With the scale-up of prenatal antiretroviral therapy to prevent maternal transmission during pregnancy, up to 98 percent of these infants may be HIV-exposed but uninfected (HEU). While understanding the short-term health consequences of intrauterine HIV exposure has been actively investigated, the long-term health outcomes of uninfected individuals into adolescence and adulthood remain largely unknown.

The MGH researchers shed light on the subject by looking at the mother's level of immune cells - known as CD4 T cells - during the last trimester of pregnancy. They found that lower maternal CD4 T cell count was strongly associated with increased body mass index (BMI), a measure of body fat based on height and weight, in their uninfected, adolescent offspring. Lower CD4 T cell count is also associated with more severe HIV infection during pregnancy. "These linkages suggest the need for good immune system control during the mother's pregnancy," emphasizes Steven Grinspoon, MD, chief, Metabolism Unit at MGH and study co-author. "Improved immune regulation may not only be good for the mother during pregnancy, but for her child over the long-term."

The comprehensive study drew on a cohort of 50 adolescents and young adults (ages 13 to 28 years old) who were HIV-exposed but uninfected (HEU), and 141 of their peers not exposed to HIV during pregnancy. All were part of the Research Patient Data Registry that includes patients from MGH, Brigham & Women's Hospital, and other affiliated hospitals. The researchers found that obesity was present in 42 percent of the HEU adolescents and young adults compared to 22 percent of their unexposed counterparts.

"It's well known that obesity in all segments of the population is associated with high blood pressure, high cholesterol and insulin resistance," notes Fourman, adding that an estimated 18 million HEU individuals younger than 15 years old currently exist throughout the world. "And studies have shown that 80 percent of obese adolescents remain obese as adults." The MGH study further showed that asthma-like symptoms occurred in 40 percent of the HEU group compared to 23 percent of its peers.

More broadly, the MGH study could help scientists gain insights into the role of the intrauterine environment in modulating the long-term health of individuals exposed in utero to a wide range of maternal conditions. For example, points out Grinspoon, "fetal exposure to maternal obesity or gestational diabetes has been linked to obesity, insulin resistance, asthma and autoimmunity later in life. The findings from our study could teach us about the effects of inflammation during pregnancy on long-term health outcomes. This is a fertile area for further investigation."

Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

Professor Denise Doolan from James Cook University's Australian Institute of Tropical Health and Medicine (AITHM) was part of an international team that narrowed down the malaria proteins and disease-fighting antibodies that could be used to develop a vaccine against severe malaria.

She said according to the latest figures from the World Health Organisation, there were 219 million cases of malaria worldwide in 2017, leading to an estimated 435,000 deaths.

"What makes this work so difficult is the particular survival strategy of the malaria parasite in the human body. It grows within blood cells and inserts proteins into the surface of the blood cell so it sticks to the walls of blood vessels," Professor Doolan said.

"But it changes these proteins to escape from immune responses, and every strain has a different set of proteins, making the identification of vaccine targets extraordinarily hard."

The team of collaborators - involving JCU, the Walter and Eliza Hall Institute of Medical Research (WEHI) at Deakin University, and malaria experts from Papua New Guinea, France and the USA - collected hundreds of PfEMP1 proteins from malaria strains from children in PNG who had been naturally infected by the disease, made a custom protein microarray of those strains, and then examined serum samples to identify which of the many PfEMP1 variants were associated with protection.

The research team managed to pinpoint which antibodies were most effective in fighting the most severe forms of malaria.

Associate Professor Alyssa Barry, who leads the Systems Epidemiology of Infection unit within the Deakin School of Medicine, said the findings from the project were a major step towards developing a viable vaccine for the disease.

"It's the first time anyone has shown this - for years, researchers have thought that developing a malaria vaccine based on PfEMP1 would be virtually impossible, because the proteins are just so diverse," Associate Professor Barry said.

"It's similar to the flu vaccine, where you have to keep adjusting and updating it as the virus strains evolve from year to year. Malaria is even more diverse than influenza - one village in a country such as PNG could contain thousands of possible malaria strains. But in malaria-endemic areas, children who are repeatedly infected develop immunity to severe malaria by the time they're about two years old, so we know antimalarial immunity is possible, and it can develop after exposure to only a few strains."

Associate Professor Barry said while immunity to milder forms of malaria presented a "formidable obstacle", immunity to severe malaria targets only a small subset of proteins that have many similarities between strains - making the essential components for a vaccine much easier to identify.

"Using genomic sequencing, we collected PfEMP1 proteins from different strains of malaria, measured antibodies to those proteins and then used machine learning to identify the protective antibody - the biomarker of immunity - that protects kids against disease," she said.

"We were able to identify these antibodies by monitoring for patterns of disease, following the children in PNG for 16 months to determine which of them were susceptible to the more severe forms of the disease, and those who were protected and only experienced milder forms of the disease.

"It's been a long road, and has involved a large team, but it's a major step forward, and this provides hope that creating a vaccine might be possible."

(Toronto, November 14, 2019) -- Mining the rich uncharted territory of the genome or genetic material of a cancer cell has yielded gold for Princess Margaret scientists: new protein targets for drug development against prostate cancer.

Using state-of-the-art, whole-genome sequencing technologies on prostate tumour samples, Princess Margaret Cancer Centre researchers focused on the often overlooked noncoding regions of the genome: vast stretches of DNA that are free of genes (i.e. that do not code for proteins), but nonetheless harbor important regulatory elements that determine if genes are turned on or off.

Previously dismissed as "junk" DNA, noncoding regions were once thought to have little to offer for a cure against cancer.

But this never dissuaded Dr. Mathieu Lupien, Senior Scientist, Princess Margaret Cancer Centre, to commit his research program to the study of the noncoding genome.

"We are exploring uncharted territory," says Dr. Mathieu Lupien, who is also an Associate Professor in the Department of Medical Biophysics, University of Toronto, whose lab's tagline is 'Decoding cancer through epigenetics.'

"Our goal is to conquer cancer in our lifetime. We have to look everywhere including the 'darkest' parts of the genome of cancer cells for that hidden 'gold'".

In his latest paper, entitled "Cistrome-partitioning reveals convergence of somatic mutations and risk-variants on master transcription regulators in primary prostate tumors" published in Cancer Cell on Thursday, November 14, 2019, Dr. Lupien and a 21-member team of national and international clinicians, scientists, pathologists and computational scientists assessed the role of more than 270,000 mutations found in primary prostate tumours.

They found that these accumulate in specific noncoding regions bound by a specific set of proteins that control the on/off state of genes. Inhibiting these proteins, which Dr. Lupien refers to as "the maestro of the cell", blocks growth of prostate cancer cells, showing their value for drug development.

This represents a new approach that exploits the rich information from all mutations found in tumours, from both coding and noncoding sources. It allows us to prioritize targets for therapy, he explains.

Just imagine the possibilities the noncoding genome opens up," he adds.

Understanding the non-coding or dark genome is an area of increasing focus for scientists.

In 2003, the Human Genome Project mapped and sequenced the human genome, consisting of all the genes necessary to grow a human being.

It found that about 21,000 protein-coding genes make up about only two per cent of our entire genome - the blueprint of life or the human genetic instruction booklet.

And the other 98% of the genome - the non-coding (for proteins) portion - what role does it play?

Scientists have come to realize that hidden amongst this noncoding DNA are crucial elements that not only control the activity of thousands of genes, but also play a major role in many diseases. Mining this area could provide important sequencing clues for potential cures.

The human genome is incredibly complicated, says Dr. Lupien. He explains that the dark or as yet undiscovered portion of the genome contains millions of gene switches, affecting all the cells in our bodies, at various points throughout our lives.

"Now we can start connecting these genetic switches to cancer development to get a more precise understanding of how disease begins and how we can treat it."

Precision medicine currently relies on a few hundred biomarker-drug combination, and we need to expand our list of biomarkers and drugs if we want to deliver on the promise of precision medicine, adds Dr. Lupien.

"The inclusion of the noncoding genome in our analysis is a leap in the right direction to achieve our goal."

The success of antiretroviral therapies has extended the lives of people living with HIV, long enough for other chronic health conditions to emerge, including a recently documented uptick in sudden death. Now, in a study comparing medical information and portable EKG patch data from men living with HIV to men without it, Johns Hopkins Medicine researchers and collaborators report they have found more variability of the electrical "reset" period between heartbeats -- known as the QT interval -- in men living with the virus, which may contribute to the increased risk of sudden cardiac deaths.

A report on the findings was published online Nov. 11 in the journal Circulation and presented Nov. 17 at the annual American Heart Association Scientific Sessions meeting in Philadelphia, Pennsylvania.

"The take-home message to patients and providers at this time is that it's still most important to treat early and control HIV infection with antiretroviral therapies, stick to therapy and continue to monitor virus levels," says lead author Amir Heravi, a medical student at the Johns Hopkins University School of Medicine. "Also, people should work to reduce traditional cardiovascular disease risk factors by following a healthy diet, keeping fit, quitting smoking and treating diabetes to compensate for any additional burden of HIV on the heart."

The researchers say, if further studies confirm and extend their findings, physicians may eventually be able to use this measure of erratic electrical activity in the heart to more precisely assess a person's risk for sudden cardiac death, and identify ways to intervene to hopefully limit or stop risk.

According to Heravi, the increase in sudden cardiac death in people living with HIV was first substantially documented in 2012 in an HIV clinic in the San Francisco Bay area, but the biological roots of the increase have remained unclear. In a bid to learn more, the Johns Hopkins researchers used data collected from the National Institutes of Health Multicenter AIDS Cohort Study (MACS), an ongoing 30-year study that follows the health of gay and bisexual men from four US cities. Specifically, they focused on medical information gathered from 534 men without HIV infection, and 589 men living with HIV, of whom 83% had undetectable levels of the virus in their blood as a result of antiretroviral therapy. Some 61% of the men self-identified as white, 25% as African American and 14% as Hispanic or "other." Participants were an average age of 57, and those with HIV had been treated for the disease for approximately 13 years.

Each participant wore a portable electrocardiogram (ECG) "patch" device to continuously measure heart rhythms. The researchers analyzed 3-4 days of data on the intervals between beats, when the electrical signals that drive heart rhythms are not firing. This electrical relaxation phase, during which the heart is preparing to send another pulse for a new beat is known as the QT interval. Variations in the length of time of the QT interval between each heartbeat in each person are well documented, and greater variation is known to increase risk for abnormal and sometimes fatal heart rhythms.

The researchers used a calculation that takes into account the heart rate and the QT interval ultimately to calculate the QT interval variability. Although a universal threshold between healthy and unhealthy levels hasn't yet been adopted, it's generally accepted that higher values translate to more heart disease and higher risk, the researchers say. They found that compared to men without HIV, men with HIV had a more variable QT interval, 0.077 greater than what would be expected for their heart rate variability. Moreover, they found this variability was also linked to the amount of virus each man carried, as measured with a blood test. The men living with HIV, but with undetectable HIV virus had an average QT interval variability of just 0.064 greater than men without HIV, whereas men with higher levels of virus had an average of 0.150 greater QT interval variability.

None of the participants experienced sudden cardiac death during the short study period. "As far as we know, our study looked at QT interval data measured during a longer period than any other," says senior study report author Katherine Wu, M.D., an associate professor of medicine at the Johns Hopkins University School of Medicine. "This was thanks to the availability of the new portable ECG patches that we could now record and analyze the heartbeats long enough to detect these changes that were associated with HIV infection."

Next, the team compared information in ways that might show how strongly the HIV link is to the QT interval variation compared to other risk factors for cardiovascular disease, such as high blood pressure, opioid use, high cholesterol levels, obesity, smoking and diabetes. Overall, they say, the data suggest that the extent of abnormal electrical relaxation variation in the heart in men living with HIV infection was comparable to that of 8 years of aging in those without detectable virus in the blood and close to 20 years of aging in those with detectable virus.

"Living with HIV with detectable virus was linked to a larger effect on QT interval variation than any other cardiovascular disease risk factor included in the study, except for diabetes," says Wendy Post, M.D., M.S., another senior study author and professor of medicine at the Johns Hopkins University School of Medicine.

Separately, the researchers collected blood samples from the participants and analyzed them for known inflammatory molecules. They found that men with HIV had 14% more of the inflammation marker IL-6, and 22% more sCD163 compared with men who didn't have HIV. They found these higher levels of inflammation were also associated with more QT variability and arrhythmia risk. As men living with HIV are known to have higher levels of inflammation, the researchers say, this finding could explain how HIV infection and the electrical system of the heart may be connected.

"HIV puts people in a state of chronic heightened inflammation and that might be a major contributor to why the heart is prone to abnormal rhythms," says Heravi. "However, inflammation would only partly explain our findings and our results showed even after adjusting for effects of inflammation, HIV infection was associated with higher QT variability. We think it may be a combination of the virus and the body's reaction to the virus via inflammation that ultimately contributes to an increased risk of sudden cardiac death."

Approximately 1.1 million people in the U.S. have HIV infections, according to the U.S. Centers for Disease Control and Prevention.

A simple blood test could soon become the latest monitoring tool for the early detection of melanoma in the eye.

University of Queensland scientists have discovered markers in the blood that can differentiate between a benign mole and a melanoma, while also identifying if the cancer has spread to other areas of the body.

University of Queensland Diamantina Institute's Dr Mitchell Stark said the blood test could monitor very early signs of the disease.

"This blood test was able to detect the difference between a benign mole located at the back of the eye and a melanoma in the eye," Dr Stark said.

"The test also has the potential to show if the melanoma has metastasised and spread to other areas of the body.

"Moles or naevi in the eye are common, but can be difficult to monitor because changes to their shape or colouring can't always be seen as easily as on the skin.

"Outcomes are poor for people with melanoma in their eye if their cancer spreads to the liver.

"Given that having naevi in the eye is fairly common, this test may allow us to better screen these patients for early signs of melanoma formation."

The study is a progression of research conducted by Dr Stark at QIMR Berghofer, where the panel of biomarkers was first developed and used to detect melanoma on the skin.

In this research, blood samples were collected from people with either benign naevi or melanoma in the back of their eye, in addition to a small number of metastasised cases.

The samples were then tested against the panel of microRNA biomarkers to distinguish the stage of disease.

Dr Stark said after further development, the blood test had the potential to be used as a monitoring tool in conjunction with optometrists, GPs, and specialists.

"If someone went to their optometrist for a regular check-up and a mole was found, you could have this blood test at each routine visit to help monitor mole changes," he said.

"If the biomarker in the blood had increased, it might be an early warning sign of melanoma.

"Knowing this patient was high-risk means they could be monitored more closely for the potential spread of cancer and be progressed more rapidly through the healthcare system."

Queensland Ocular Oncology Service Director and ophthalmologist Dr Bill Glasson AO said the test would be extremely helpful in clinical practice.

"These research findings are exciting for our patients with ocular tumours," Dr Glasson said.

"It will allow for earlier diagnosis as well as giving doctors an earlier indication of the development of metastatic disease and importantly, a better outcome for our patients."

In June, the International Energy Agency confirmed what most experts already know: that the world should work harder to boost the use of pure hydrogen as an emissions-free energy source.

One of the challenges of creating hydrogen, however, is that it takes energy--lots of energy. The IEA says that producing all of today's hydrogen just using electricity would require 3600 TWh, which is more than is generated annually by the European Union.

But what if you could use an existing source of wasted energy to help with hydrogen production? A new approach developed by researchers at the Norwegian University of Science and Technology does exactly this -- by using waste heat from other industrial processes.

"We've found a way of using heat that otherwise isn't worth much," said Kjersti Wergeland Krakhella, the first author of an article about the process published in the academic journal MDPI Energies. "It's low-grade, low-temperature heat -- but it can be used to make hydrogen.

One-seventh of Norway's electricity production

Waste heat is exactly what it sounds like -- heat produced as a byproduct of an industrial process. Anything from an industrial boiler to a waste-to-energy plant produces waste heat.

More times than not, this excess heat has to be released to the environment. Energy experts say that the waste heat from Norway's businesses and industries is the equivalent of 20 TWh of energy.

To put this in perspective, Norway's entire hydropower system produces 140 TWh of electricity a year. That means there's a lot of waste heat out there that could potentially be put to work.

Membranes and salts

The researchers used a technique called reverse electrodialysis (RED), which relies on salt solutions and two varieties of ion exchange membranes.

To understand what the researchers actually did, you first have to understand how the RED technique works.

In RED, one membrane, called the anion exchange membrane, or AEM, allows negatively charged electrons (anions) to move through the membrane, while a second membrane, called the cation exchange membrane, or CEM, allows positively charged electrons (cations) to flow through the membrane.

The membranes separate a dilute salt solution from a concentrated salt solution. The ions migrate from the concentrated to the dilute solution, and because the two different types of membranes are alternated, they force the anions and cations to migrate in opposite directions.

When these alternating columns are sandwiched between two electrodes the stack can generate enough energy to split water into hydrogen (on the cathode side) and oxygen (on the anode side).

This approach was developed in the 1950s and first used saltwater and river water.

What Krakhella and her colleagues did, however, was to use a different kind of salt called potassium nitrate. The use of this kind of salt enabled them to use waste heat as part of the process.

Reusing the salts using waste heat

If you run the RED stacks described above, at some point the concentrate and dilute salt solutions become more and more alike, so they have to be refreshed.

That means you need to find a way to increase the concentration of the salt in the concentrated solution and remove salt from the dilute solution. That's where the waste heat comes in.

The researchers tested two systems.

The first was where waste heat was used to evaporate water from the concentrated solution to make it more concentrated.

The second system used waste heat to cause salt to precipitate out of the diluted solution (so it will be less salty).

"If you find a way to remove the water or remove the salt, you have done the job," Krakhella said.

Both had benefits

When the researchers looked at their results, they saw that using existing membrane technology and waste heat to evaporate water from their system produced more hydrogen per membrane area than the precipitation approach.

The production of hydrogen was four times higher for the evaporation system operated at 25 C and two times higher for a system operated at 40 C compared to their precipitation system.

That made it a better candidate from a cost perspective.

However, the precipitation process was better in terms of energy demand, the researchers found. For example, the energy needed to produce a cubic meter of hydrogen using the precipitation process was just 8.2 kWh, compared to 55 kWh for the evaporation process.

New system with many possibilities

While Krakhella's work proves the concept will work, she's mostly worked with a lab bench model and lots of computer calculations. There's still lots of work to be done, especially with respect to the kind of salt used in the process.

The researchers chose potassium nitrate for their salt system, but other salts could also work, she said.

"It's a completely new system," she said. "We'll need to do more testing with other salts at other concentrations."

Membrane prices are limiting factor

Another issue that continues to limit hydrogen production is that the membranes themselves remain extremely costly.

Krakhella hopes that as societies look to move away from fossil fuels, increased demand will drive the price of membranes down, as well as improving the characteristics of the membranes themselves.

"The membranes are the most expensive part of our system," Krakhella said. "But everyone knows we need to do something about the environment, and the price is potentially much higher for society if we don't develop pollution-free energy."

The Chinese government may have been systematically misreporting the number of organs it claims it has voluntarily collected since 2010, according to new research published in BMC Medical Ethics.

In 2015 China promised the world they would no longer source organs from prisoners - their almost sole source previously.

The study, led by PhD scholar Matthew Robertson from The Australian National University (ANU), used statistical forensics on official Chinese datasets.

"Our research shows Beijing's reported organ donation numbers don't stack up and there is highly compelling evidence that they are being falsified," Mr Robertson said.

"The figures appear to have been based on a simple mathematical formula, a quadratic function, which would be familiar to many high school students.

"When you take a close look at the numbers of organs apparently collected they almost match this artificial equation point for point, year in, year out. They're too neat to be true.

"These figures don't appear to be real data from real donations. They're numbers generated using an equation.

"It is difficult to imagine how this model could have been arrived at by mere chance, raising the distinct possibility that it was intended to deceive."

The study looked at data on voluntary hospital-based donated organs between 2010 and 2018 published by the China Organ Transplant Response System and the Red Cross Society of China*.

"We found major anomalies with the datasets, with implausibly high ratios of transplants per donor and mismatches when the two sets of data were meant to be identical," Mr Robertson said.  

"Provincial and hospital-level data we examined also showed anomalies that are extremely difficult to explain.

"The implication is that it is highly likely the numbers the Chinese government have put out were not actually real figures created by actual organ donations, but instead generated by a simple mathematical formula."

The researchers also found the misclassification of non-voluntary organ donors as voluntary.

"This is all highly suggestive evidence of data manufacturing and manipulation that could only have been done by human intervention," Mr Robertson said.

"The patterns we observed in the data can only be plausibly explained by the falsification of official organ transplant figures."

The China Organ Transplant Response System (COTRS) forms the basis of China's current voluntary organ donation reforms, with every organ transplant allocated solely through it.

The Red Cross Society of China is mandated to verify and witness every such organ donation.

While data from COTRS is not usually publicly available, data from it has been published twice - in 2014 and in 2017.

Data from the Red Cross Society of China was previously available on four websites, with three of the websites recently taken offline. The dataset is currently available at http://www.codac.org.cn.  

The researchers' findings have been reviewed by one of the world's leading statisticians - Sir David Spiegelhalter, former president of the Royal Statistical Society in the UK.   

"The anomalies in the data examined...follow a systematic and surprising pattern," Spiegelhalter wrote.

"The close agreement of the numbers of donors and transplants with a quadratic function is remarkable and is in sharp contrast to other countries who have increased their activity over this period... I cannot think of any good reason for such a quadratic trend arising naturally."

Mr Robertson and his team's research comes just months after the findings of the China Tribunal, led by the former UN war crimes prosecutor Sir Geoffrey Nice QC.

The tribunal concluded that "in China forced organ harvesting from prisoners of conscience has been practiced for a substantial period of time involving a very substantial number of victims".

Mr Robertson said the study's findings were globally significant.

"China's much-heralded organ transplant reform program was supposed to be the culmination of over a decade of international pressure, where finally they were reforming and ceasing the use of organs from prisoners," Mr Robertson said.

"As a result of these promises to reform, the same Chinese officials who promulgated this data were welcomed into the World Health Organization's transplantation task force, and Chinese surgeons began presenting in medical conferences again.

"Now we have found that the data was simply made up, based on an equation.

"With what our study shows, we think it is important the world take a closer look at China's organ transplantation system."

Subarachnoid haemorrhage is a severe stroke subtype that is caused by a rupture of a brain aneurysm, an enlargement in brain vessel wall.

Up to one in four subarachnoid haemorrhage patients die quickly after the bleed at home, on the road to a hospital, or in an emergency room. These patients never reach hospital wards and are often incorrectly diagnosed. In many countries, these sudden deaths are classified as sudden cardiac deaths since routine autopsies are rarely conducted outside Nordic countries.

If only patients who survive the initial bleed and reach hospital wards are included in studies on risk factors of subarachnoid haemorrhage, such studies are very likely biased, because they are unable to study risk factors relating to the most devastating outcome, namely sudden death.

Two recent hospital-based studies, that excluded patients who died before reaching hospital wards, reported that smokers and hypertensive individuals have better chances to survive from subarachnoid haemorrhage than non-smokers and those with normal blood pressures.

These findings puzzled researchers and clinicians, because they contradicted earlier reports. For decades, the researchers and clinicians have known that smoking and high blood pressure are the two most important risk factors for subarachnoid haemorrhage, but now the studies suggest that the same factors would paradoxically protect from subarachnoid haemorrhage-related death.

A Finnish study, published in the distinguished Neurology journal, shows that when researches are able to include those people who die before reaching hospital wards, the paradoxical protective effect of smoking and high blood pressure is reversed. Specifically, the study showed that smokers and hypertensive individuals die more frequently before they reach hospital wards than non-smokers and those with normal blood pressure. When these heavy smokers and hypertensive people are left out from statistical analyses, the results are misleading.

"Due to the mandatory autopsies for all sudden deaths in Finland, we were able to identify and include data on those individuals who died before reaching hospital wards. This in turn allowed us to show how results change when all people with subarachnoid haemorrhage, not only those surviving to hospitals, are included in the analyses." says physician Joni Lindbohm, the principal author of the research article.

"In practise, our results show that risk factor and survival estimates of subarachnoid haemorrhage from studies that exclude people dying quickly after the bleed are unreliable. This is important to recognize because most subarachnoid haemorrhage studies are still hospital-based and do not include data on sudden deaths," neurosurgeon, Dr. Miikka Korja states.

According to Lindbohm and Korja, the best way to minimize the risk to sudden death from subarachnoid haemorrhage is to quit smoking and lower elevated blood pressure values.

An abdominal aortic aneurysm is a focal dilation of the abdominal aorta, that if not treated, tends to grow and may rupture. The most common treatment is EndoVascular Aneurysm Repair (EVAR), which requires patients to undergo lifelong postoperative surveillance based on computed tomography angiography (CTA) due to the possible appearance of complications. These complications may again lead to aneurysm dilation and rupture.

To monitor the disease, advanced tools for the quantitative analysis of clinical images to support physicians are lacking. Currently, the approach consists of evaluating diameter changes to the aneurysm along time to infer the progress of the patient and the postoperative risk of aneurysm rupture. An increased diameter is usually associated with a higher rupture risk, but there are some small aneurysms that rupture, whereas other larger ones remain stable.

This means that diameter-based rupture risk assessment is not suitable for all cases, and there is increasing evidence that the biomechanical behaviour of the aneurysm may provide additional valuable information regarding the progression of the disease and the risk of rupture.

A study published recently in Frontiers in Bioengineering and Biotechnology, coordinated by Miguel A. González Ballester (ICREA-DTIC) and Iván Macía (VicomTech), offers a promising methodology for post-operative CTA time-series registration and subsequent aneurysm biomechanical strain analysis, which correlates with the patient's long-term prognosis.

The study was conducted entirely in Catalonia and the Basque Country by researchers from the BCN-MedTech Research Unit of the Department of Information and Communication Technologies (DTIC) at UPF, together with the centres in the Basque Country: VicomTech Foundation of San Sebastián, the Bioengineering area of the BioDonostia Health Research Institute and Donostia University Hospital.

Quantitative descriptors extracted from registrations of deformations of the aorta

From the deformations obtained from CTA image registration, the researchers have extracted quantitative descriptors of the main components of the tensile and compressive strain fields. "Evaluated on 22 patients, our approach yields a mean area under the curve of 88.6% when correlating the strain-based quantitative descriptors with the long-term patient prognosis", says Karen López-Linares, first author of the work, linked to the SIMBIOsys research group and researcher at BCN-MedTech, the VicomTech Foundation and the BioDonostia Health Research Institute.

"This suggests that the descriptors directly extracted from the CTA images are able to capture the biomechanical behaviour of the aneurysm without relying on finite element modelling and simulation", add Jérôme Noailly, a specialist in computational biomechanics, and Miguel A. González Ballester (ICREA DTIC), both members of BCN-MedTech and co-authors of the article.

Biomarkers for the most difficult and uncertain cases of aneurysm

In addition, the authors highlight that the extracted descriptors set the basis for possible future imaging biomarkers that may be used in the clinical practice. These biomarkers may be used to assess patient prognosis and to enable informed decision making after an EVAR intervention, the most common treatment for aortic and abdominal aneurysms, and especially in difficult, uncertain cases.

Women exposed simultaneously to stress and plastic additives late in pregnancy are at increased risk for premature birth, according to a study by Rutgers and other institutions.

The study, published in the journal Environment International, is the first to analyze a link between stress and phthalates - a group of chemicals in plastics, personal care products and electronics - and premature births. The findings are the latest in the Infant Development and the Environment Study, which tracked 783 women throughout their pregnancies between 2010 and 2012.

"Both exposure to phthalates and high levels of stress have been individually linked to births before 37 weeks gestation, but how these two risk factors may influence each other had not been previously explored," said co-author Emily Barrett, an associate professor at Rutgers School of Public Health and Environmental and Occupational Health Sciences Institute. "Our research suggests that the third trimester is the critical window for these risks."

People are exposed to phthalates by eating and drinking foods from containers and products containing the chemicals, through packaging and food handling equipment, through their skin in personal care products and in the air they breathe.

While stress itself is not related to the exposure of these plastic additives, stress can affect the immune system, lead to inflammation and change hormone levels, potentially making these women more vulnerable to the adverse effects of phthalates.

Barrett said other factors - how a woman perceives stress, how she uses social supports to lessen stress and the total number of stress events in her life - can affect how stress during pregnancy affects her child's health. The researcher recommends that pregnant women limit their exposure to phthalates by eating less processed foods and reducing use of plastics and personal care products.

The researchers analyzed urine samples throughout the women's pregnancies for traces of phthalates and reviewed questionnaires they completed in their third trimester about stressful events - such as job loss, serious illness, family death, relationship difficulties and legal or financial problems - during their pregnancies. About nine percent of the women delivered prematurely, 70 percent of which were spontaneous.

"Mothers who had higher levels of phthalates in their urine and reported stress during their pregnancy as well were more likely to give birth preterm," Barrett said. "We think that stress may make the body more vulnerable to the impacts of chemicals in our environment, like phthalates."

Washington, DC, November 14, 2019- A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that home-visiting by trained community workers during and after pregnancy can improve mother-child interactions in the first years of life. However, this benefit was not found for mothers who experienced depressive symptoms during pregnancy.

"The quality of close relationships early in life has a lasting impact on children's development," said lead author Joan Christodoulou, a postdoctoral scholar at University of California, Los Angeles's Global Center for Children and Families in Los Angeles, CA, USA. "Caregiving that is sensitive, or responsive to a child's needs and engages the child, with limited hostility, may be a particularly important factor in mediating the adverse effects on development for children growing up in poverty."

The findings are based on the results of a cluster randomized controlled trial, jointly-investigated by researchers at UCLA and South Africa's Stellenbosch University. Evaluating the Philani Program in Cape Town, South Africa, pregnant mothers in 24 local township neighborhoods were recruited into the
study; 98 percent were enrolled and followed from pregnancy through to five-years post-birth. A representative cohort of 1,239 pregnant township mothers were studied.

Mothers in the intervention received home visits by community workers trained by the Philani Program from May 2009 to September 2010. Over the next five years, researchers tracked data related to maternal- and child-health including depression, HIV, food security, caregiving, as well as the quality of mother-child interactions.

The authors found that mothers who received home visits displayed more maternal sensitivity, talked to the infant more and had more harmonious interactions with their children. They also have children who paid more attention and were happier than their peers at three years post-birth. However, mothers who had depressive symptoms during pregnancy did not experience these benefits.

Home-visiting by trained community health workers resulted in a better quality of caregiving for mothers without depressive symptoms in a low and middle income country. Future maternal and child health interventions need to specifically target maternal depression during and after pregnancy.

ANN ARBOR--Everyone knows that gaining excess weight during one pregnancy is bad, but clinicians rarely consider weight gains and losses from one pregnancy to the next--especially in normal-weight women.

But researchers from Marquette University and the University of Michigan found that among normal-weight women, fluctuating weight gain and loss in the first pregnancy is often repeated in subsequent pregnancies--and is associated with higher risk of several pregnancy-related complications.

Interestingly, obese women are not as likely to fall into this weight gain-loss cycle as normal-weight peers, the researchers say. Normal weight is defined as having a BMI less than 25.

"Normal-weight women gain more pounds and also lose more after giving birth," said Marianne Weiss, professor emerita of nursing at Marquette. "This cycle perpetuates with each pregnancy, and it's this rollercoaster weight gain and loss --not just what a woman typically weighs--that predicts poor pregnancy outcomes."

"This study says two things," said Olga Yakusheva, associate professor at the U-M School of Nursing and School of Public Health. "First, don't just look at how much a woman weighs at the first prenatal visit; you have to know her recent pattern of weight gain and loss. Second, pregnancy weight counseling and management should be given equally to all women, not just the ones who are very overweight."

The researchers, who examined 24,795 linked birth records from 2006 to 2013, say first-pregnancy weight gain and subsequent weight loss after birth starts this unhealthy rollercoaster--which in turn increases the risk for gestational diabetes, hypertension, cesarean delivery and fetal macrosomia (bigger-than-average baby) in the next pregnancy.

The study showed that compared with obese women, normal-weight women gained about 6.6 pounds (3 kg) more during both pregnancies and lost about 4.4 pounds (2 kg more) between births.

This surprised Yakusheva.

"I thought that if a lot of weight is gained in the first pregnancy and it was all lost before the second pregnancy, then you're no longer at risk," she said. "Something I didn't consider is that you can be normal weight in the first pregnancy, gain a lot of weight and then lose it before the second pregnancy, and still be at a higher risk of gaining a lot of weight and having negative outcomes in the second pregnancy."

This gain-lose-gain cycle and associated poor pregnancy outcomes reflects Yakusheva's own experience with her two children. Despite rigidly following clinical guidelines with her first child, she added 65 pounds to her 112-pound frame. Neither Yakesheva nor her clinicians noticed or addressed it--she's thin, so weight gain wasn't on anyone's radar.

"I remember the nurses telling me, 'Don't worry about your weight gain, you're tiny,'" she said. "Looking back, I don't think that was healthy for me to hear."

Yakusheva lost the weight before her second pregnancy, yet despite her history, clinicians again didn't address weight gain. Rather, she took it upon herself to monitor her weight.

This doesn't mean weight isn't important, but looking only at weight is myopic, the researchers say. What's more important is how a woman has managed her weight gain and loss in previous pregnancies.

"The bottom line is that women and their perinatal care providers need to pay attention to appropriate weight before, during, and after each pregnancy to set the stage for optimal outcomes in the next pregnancy," Weiss said.

WINSTON-SALEM, N.C. - Nov. 14, 2019 - Scientists have reported a new approach to treating lung cancer with inhaled nanoparticles developed at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

In this proof of concept study, Dawen Zhao, M.D., Ph.D., associate professor of biomedical engineering at Wake Forest School of Medicine, used a mouse model to determine if metastatic lung tumors responded to an inhalable nanoparticle-immunotherapy system combined with the radiation therapy that is commonly used to treat lung cancer.

The study is published in the current issue of Nature Communications.

Lung cancer is the second most common cancer and the leading cause of cancer death among both men and women. More people die of lung cancer than of colon, breast and prostate cancers combined. Although immunotherapy is promising, it currently works in less than 20% of patients with lung cancer.

Significant clinical evidence suggests that at the time of diagnosis most patients' tumors are poorly infiltrated by immune cells. This "cold" immune environment in tumors prevents the body's immune system from recognizing and eliminating the tumor cells.

Overcoming this immunosuppressive tumor environment to attack the cancer efficiently is currently an area of great interest in the scientific community, Zhao said.

Previous approaches have involved direct injection of immunomodulators into tumors to boost their immune response. However, this approach is generally limited to surface and easily-accessed tumors, and can become less effective if repeated injections are needed to sustain immune response.

"The goal of our research was to develop a novel means to convert cold tumors to hot, immune-responsive tumors," Zhao said. "We wanted it to be non-invasive without needle injection, able to access multiple lung tumors at a time, and be safe for repeated use. We were hoping that this new approach would boost the body's immune system to more effectively fight lung cancer."

The nanoparticle-immunotherapy system that Zhao and his team developed delivered immunostimulants via inhalation to a mouse model of metastatic lung cancer. The immunostimulant-loaded nanoparticle which, when deposited in the lung air sacs, were taken up by one specific type of immune cells, called antigen-presenting cells (APC).

The immunostimulant, cGAMP, in the nanoparticle was then released inside the cell, where stimulation of a particular immune pathway (STING) activated the APC cell, which is a critical step to induce systemic immune response.

The team also showed that combining the nanoparticle inhalation with radiation applied to a portion of one lung led to regression of tumors in both lungs and prolonged survival of the mice. In addition, the team reported that it completely eliminated lung tumors in some of the mice.

Through mechanistic studies the team then confirmed that the inhalation system converted those initially cold tumors in both lungs to hot tumors favorable for robust anti-cancer immunity.

Zhao's inhalable immunotherapy presents several key advantages to previous methods, especially the ability to access deep-seated lung tumors because the nanoparticulate-carrying aerosol was designed to reach all parts of the lung, and the feasibility of repeated treatment by using a non-irritating aerosol formulation.

The treatment was shown to be well tolerated and safe without causing adverse immune-related distress in the mice.

The Wake Forest School of Medicine researchers have filed a provisional patent application for the inhalable nanoparticle-immunotherapy system.