Body

LONDON, ON - Neurofeedback, also called 'brain training,' consists of exercises where individuals regulate their own brain activity. In a new study from Lawson Health Research Institute and Western University, researchers have found that neurofeedback may be an effective treatment for individuals with post-traumatic stress disorder (PTSD). Published in NeuroImage: Clinical, the clinical trial found that neurofeedback was effective in reducing symptoms of PTSD.

"Brain connectivity involves different parts of the brain communicating with each other and helps to regulate states of consciousness, thought, mood and emotion," explains Dr. Ruth Lanius, scientist at Lawson, professor at Western's Schulich School of Medicine & Dentistry and psychiatrist at London Health Sciences Centre. "Individuals with PTSD tend to have disrupted patterns of brain connectivity, but our research suggests they can exercise their brains to restore patterns to a healthy balance."

Neurofeedback uses a system called a neurofeedback loop in which a person's brain activity is measured through sensors placed on the scalp and displayed back to them using a computer interface. This allows the individual to complete exercises and visually see the results.

The trial tested neurofeedback with a total of 72 participants, including 36 participants with PTSD and 36 healthy control participants. Of those with PTSD, 18 were randomized to participate in neurofeedback treatment while the other 18 acted as a comparison group.

The study found that the severity of PTSD symptoms decreased in participants randomized to receive neurofeedback treatment. After treatment, 61.1 per cent of participants no longer met the definition for PTSD. This remission rate is comparable to gold standard therapies like trauma-focused psychotherapy.

The research team also used functional magnetic resonance imaging (fMRI) at St. Joseph's Health Care London to capture brain scans of participants both before and after participation in the trial. They found that individuals with PTSD experienced positive changes in brain connectivity in the salience network and the default mode network following neurofeedback treatment.

"The salience network is involved in detecting threat as part of the 'fight or flight' response. It is normally hyperactive in individuals with PTSD. Meanwhile, the default mode network is activated during rest and is involved in autobiographical memory. We often see that this network is less active during rest and functionally disrupted among individuals with PTSD," says Dr. Andrew Nicholson, affiliated scientist at Lawson. "Neurofeedback helped restore the functional connectivity of both networks to healthier levels." Dr. Nicholson is an assistant professor at McMaster University and was formerly a post-doctoral fellow at Schulich Medicine & Dentistry.

The study involved weekly sessions of neurofeedback over 20 weeks. Participants were asked to reduce the intensity of the brain's dominant brain wave - the alpha rhythm. Brain activity was visualized as either a still cartoon or a distorted picture. If the alpha rhythm was successfully reduced, the cartoon started playing or the picture started becoming clearer.

"Participants were not instructed on how to reduce the alpha rhythm. Rather, each individual figured out their own way to do so," notes Dr. Lanius. "For example, individuals reported letting their mind wander, thinking about positive things or concentrating their attention."

The team notes the treatment could have a number of clinical implications following further validation.

"Neurofeedback could offer an accessible and effective treatment option for individuals with PTSD," says Dr. Lanius. "The treatment is easily scalable for implementation in rural areas and even at home."

PITTSBURGH, 26 January 2021 - A vaginal ring containing the antiretroviral drug dapivirine and the contraceptive hormone levonorgestrel delivered sustained levels of each drug when used continuously for 90 days - levels likely sufficient to serve its dual purpose for protecting against both HIV and unwanted pregnancy, according to findings of a new study.

Results of the Phase I study of the 90-day dual-purpose ring are being presented at the HIV Research for Prevention (HIVR4P) Virtual Conference, or HIVR4P // Virtual, which is taking place over the course of four days: Jan. 27-28 and Feb. 3-4.

The study, MTN-044/IPM 053/CCN019, was conducted by researchers from the National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN) in collaboration with NIH's Contraceptive Clinical Trials Network (CCTN) and is the first to evaluate the ring's use, as intended, for 90 days. In an earlier first-in-human study (MTN-030/IPM 041), also conducted by the MTN, women used the ring for 14 days with no safety concerns.

The 90-day dual-purpose ring is one of two next-generation vaginal rings being developed by the nonprofit International Partnership for Microbicides (IPM) - the other being a 90-day dapivirine-only ring for HIV prevention alone. Both products build on IPM's monthly dapivirine ring, which last year received a positive opinion from the European Medicines Authority (EMA) for its use among cisgender women ages 18 and older in developing countries, and soon after, was added to the World Health Organization (WHO) list of pre-qualified medicines. IPM is now seeking the ring's approval in several African countries, as well as from the U.S. Food and Drug Administration. If approved, the monthly dapivirine ring would be the first biomedical HIV prevention method designed specifically for cisgender women and the first long-acting method.

"It is so exciting to see the dapivirine ring nearing the finish line, and we can only hope that other HIV prevention products for women will follow. If there's one thing we've learned from our experience with contraception uptake and delivery, it's important that women have options, because they have different needs and preferences at different times in their lives," says Sharon L. Achilles, M.D., Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and director of the Magee-Womens Research Institute's Center for Family Planning Research.

"That's why a product that could protect against both HIV and unwanted pregnancy might be especially attractive to many women," added Dr. Achilles, who is protocol chair of the MTN-044/IPM 053/CCN019 study and will be reporting its results at the meeting. Dr. Achilles led the first Phase I study as well.

Whereas the monthly ring contains 25 mg of dapivirine, the dual-purpose ring contains 200 mg of dapivirine to allow for its extended release over three months, as well as 320 mg of levonorgestrel, a synthetic progestin used in many contraceptives, either alone or in combination with estrogen.

Because irregular bleeding or spotting is a common side effect of progestin-only contraceptives, Dr. Achilles and her team wanted to know whether the same would be true with use of the 90-day ring and whether removing the ring for a couple days each month, as is commonly done for other contraceptives, would reduce or eliminate irregular bleeding. Importantly, the study aimed to determine whether there would be sustained release of dapivirine and levonorgestrel over the course of 90 days - at levels thought to be sufficient for HIV protection and contraception - and the impact that periodic removals of the ring might have. This would be especially important to understand, because as a user-controlled method, it is likely to be removed from time to time anyway.

The study enrolled 25 women at Magee-Womens Hospital of UPMC in Pittsburgh, who were randomly assigned to use the combination dapivirine-levonorgestrel ring continuously for 90 days or cyclically for 90 days - three cycles during which the ring was used for 28 days and removed for two days.

Bleeding patterns experienced by participants were nearly identical in the two groups, and generally reassuring. Of the more than 2,100 total days of ring use across both groups, 58 percent were without bleeding and 31 percent only spotting. Likewise, moderate bleeding was reported to occur only 10 percent of the days and heavy bleeding only accounted for 1-2 percent of the days in each group. There were no significant product-related safety concerns.

When the ring was in place, the amount of dapivirine in plasma was well above levels observed in the Phase III efficacy trials of the 25 mg ring. While dapivirine levels decreased when the ring was removed, they remained within the range seen in the Phase III trials with the lower dose ring. Likewise, levonorgestrel levels in plasma remained consistent with those required for effective contraception. With respect to dapivirine levels in vaginal fluid, there was a rapid and steep decline after the ring's removal.

"Because cyclic use is a common practice with many hormonal contraceptives, and, as a user-controlled product, periodic removal of the ring can be expected, we wanted to understand the impact this behavior would have on both bleeding patterns and HIV protection. So far, it does not appear likely that cyclic use will make a difference in bleeding patterns, but it remains to be seen whether or not periodic removals will allow for sustained protection against HIV infection. This is something that we will need to study further," commented Dr. Achilles.

While adherence to ring use was high - about 91 percent - more than 25 percent of the participants said they removed the ring at least once during the study. At the same time, 19 of the 25 participants, or 76 percent, reported that their ring partially come out on its own on one or more occasion and that for 10 women (40 percent), the ring fell out completely at least once. Unlike the monthly and 90-day tenofovir rings, the combination dapivirine-levonorgestrel ring evaluated in the study was made to be more pliable and had a softer feel, which the researchers believe is the likely reason for the many expulsions. IPM has since reformulated the ring, which it now plans to evaluate in a trial to be conducted in partnership with the CCTN, part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

"We have heard from women around the world that they want and need new multipurpose prevention choices they can use on their own terms. Today's encouraging results support the continued development of the dapivirine-contraceptive ring, and we are working to incorporate the valuable insights gained from this study to optimize the ring's formulation," said Bríd Devlin, IPM's executive vice president for product development. "We are optimistic that the dapivirine-contraceptive ring will further expand women's sexual and reproductive health choices."

The results of the MTN-044/IPM 05/CCN019 study will be presented by Dr. Achilles in a session called "Multipurpose prevention technologies (MPTs) for prevention of HIV and pregnancy," which is part of the Jan. 28 program of HIVR4P // Virtual.

Also to be reported in the same session are preliminary results of MTN-045, or the CUPID Study, which involved interviews with 400 couples in Uganda and Zimbabwe about their views and preferences for potential dual-purpose products. More than 90 percent of the couples liked the idea of a two-in-one product, especially if framed first, and foremost, as a contraceptive rather than a method for HIV prevention.

Results of the Phase I study (MTN-036/IPM 047) of the 90-day dapivirine-only ring have been accepted for presentation at the upcoming Conference on Retroviruses and Opportunistic Infections (CROI), March 7-10.

The prevalence of inflammatory bowel diseases has significantly increased both in Finland and globally. These disorders cannot be entirely cured. Instead, they are treated with anti-inflammatory drugs and, at times, through surgery.

If conventional drug therapies based on anti-inflammatory drugs are ineffective, the diseases can be treated using infliximab, a biological TNF-α blocker that is administered intravenously. Infliximab is an antibody that prevents TNF-α, a pro-inflammatory factor, from binding with inflammatory cells in the intestine. It is effective in reducing inflammation and improving the patient's condition, while also controlling the disease well.

Although infliximab therapy is often effective, roughly 30-40% of patients either do not respond to the treatment or lose response over time. So far, no reliable tests for predicting treatment response are available.

"A test for predicting responses would help to choose drug therapies and avoid unnecessary drug use, which would reduce potential adverse effects and save on drug expenses in the healthcare system," postdoctoral researcher Eija Nissilä says.

In a collaborative project, the University of Helsinki and the Department of Gastroenterology at the Helsinki University Hospital investigated whether any predictors associated with infliximab therapy could be identified in the gut microbiota. The results were published in the Journal of Crohn's and Colitis.

The study revealed that already before treatment the gut microbiota of inflammatory bowel disease patients differed in terms of several bacterial and fungal genera. These differences had a link to infliximab therapy response.

The changes that occurred in the gut microbiota during therapy also differed between patients who presented a response to treatment and those who did not. The gut of non-responsive patients had fewer anti-inflammatory bacteria of the Clostridia family and a higher number of pro-inflammatory bacteria and fungi such as Candida. Certain bacteria found in the intestine predicted a good response to infliximab therapy.

Based on the results, gut bacteria and fungi could potentially be used as indicators when assessing whether to initiate treatment or not.

"Such a predictive test would make it possible to choose the appropriate therapy, providing savings in drug therapy costs in healthcare," Nissilä notes.

A study performed by the Universitat Oberta de Catalunya (UOC) provided eight recommendations for improving the online technology to help with the treatment and diagnosis of neglected tropical diseases (NTDs). The analysis, presented in a recent open-access publication, was performed by UOC researchers Carme Carrion and Marta Aymerich from the eHealth Lab and Noemí Robles from the eHealth Center, together with José Antonio Ruiz Postigo from the World Health Organization and Oriol Solà de Morales from the Health Innovation Technology Transfer Foundation. In the study, the authors looked at the context of the existing apps and identified their weaknesses.

The recommendations, outlined in this infographic prepared by the UOC eHealth Center, are the result of analysing 13 apps out of a total of 133 candidates, and highlight both their weaknesses and their possibilities for improvement. The goal is to standardize and improve the apps developed for controlling and monitoring neglected tropical diseases of the skin, an even more neglected subgroup of NTDs.

Neglected tropical diseases affect more than a billion people and cause hundreds of thousands of deaths every year. In spite of this, most people still know very little about them. This is the second year that the World NTD Day has been held on 30 January.

More efficient, better uptake

The recommendations given by Carrion's team in the form of a guide provide an initial base for improving the efficiency in the development and social uptake of apps designed for the control and treatment of NTDs. These recommendations are summarized in eight points:

Nobody should be left out: patients from all regions should be selected to benefit from the proposed interventions. This requires translating the tools into different languages. At the very least, into Portuguese and Spanish in the Americas; and English, French and Portuguese in Africa.

Users must have control: the interventions' end users (health professionals and patients) must be given sufficient training to improve their digital literacy and make effective use of the tools that are provided.

Complexity must be adequately catered for: integrating e-health-related technology is a complicated process that should be considered in depth both before and during implementation.

Utility and simplicity must be there, and, what is more, they must be seen: health professionals, patients and healthy citizens must be able to understand the proposed technology's utility and ease of use. In other words, it must be a facilitator, not a barrier.

The technological requirements must be considered from the beginning: the availability of adequate mobile devices, the potential problems with electricity supply or internet networks, and other technical issues must be considered as part of a comprehensive strategy with a specific objective.

A long-term m-health platform must be established: an m-health intervention's success depends on the existence of a platform that makes it easier not only to implement the tool but also guarantees its sustained, effective use.

Split-level processes are required to improve: in the early stages of implementation of an m-health system, the processes must be divided into two levels in order, first, to refine the process and, then, to optimize it iteratively.

The tool must meet the stated needs: interventions are integrated in a specific health service; accordingly, additional tools should be considered as required.

One of the main challenges faced by this type of app, explained Carme Carrion, also affiliated with the UOC's eHealth Center, is the digital divide, but not in its connotation as a knowledge problem: "The technological features are limited. You can't design interventions that can only be used by a few people, because that widens the health gap and inequality," said the expert. "You've got to look for simple, cheap solutions that leave no one behind, that can be taken to everyone, and not just these communities' socioeconomic elites. That's where the challenge is."

E-health: an opportunity

"There are a series of problems in the countries where these diseases are endemic," explained this expert in e-health solutions. "For example, access to mobile devices by the population, broad band, reliable internet connections, batteries [...]. The number of existing apps related with tropical skin diseases is small. Compared with other, more general health apps, there are few apps available, even in Google Play or Apple Store. And the few that exist have virtually no scientific articles to back them," she continued.

"WHO - who the UOC works with closely on increasing awareness of the NTDs - has been promoting m-health in these countries for more than 10 years, precisely because, in certain areas, in spite of the difficulties, it is much easier to communicate with a mobile phone and make video calls than to transport people physically." However, "in order to do it well, we must have information that reviews the apps' quality," added the researcher, in order to improve their integration and the services that help combat this type of disease.

CHAMPAIGN, Ill. -- The Medicaid expansion facilitated by the Affordable Care Act led to increases in the identification of undiagnosed HIV infections and in the use of HIV prevention services such as preexposure prophylaxis drugs, says new research co-written by a team of University of Illinois Urbana-Champaign experts who study the intersection of health care and public policy.

The research by Dolores Albarracín, a professor of psychology and of business administration at Illinois, and Bita Fayaz Farkhad, an economist and a postdoctoral researcher in psychology at Illinois, found that expanding eligibility for Medicaid, the federal-state health insurance program for low-income individuals, was associated with a 13.9% increase in HIV diagnoses.

The newly discovered infections were concentrated among those likely to be affected by the health insurance expansion: individuals engaged in injection drug use in low-income and rural counties with a high share of pre-ACA uninsured rates.

The changes in new HIV diagnoses, awareness of HIV status and additional PrEP use were not simply due to an increase in HIV infections or to an increase in infection risk, but to the expanded access of health insurance through the Medicaid program, the researchers said.

"We find that HIV diagnoses increased in Medicaid expansion states compared with nonexpansion states, and that the general knowledge that HIV can be prevented through prophylaxis drugs also increased," said Farkhad, the lead author of the research. "When we consider these two findings together, our conclusion is that access to health care and health insurance has increased the percentage of people living with HIV who are aware of their status, which is an important finding for HIV prevention efforts. According to 2016 Centers for Disease Control and Prevention estimates, a high proportion of new HIV infections were transmitted by people who were unaware of their HIV-positive status."

"Increasing community awareness of HIV and increasing individuals' awareness of their HIV status is key to reducing new infections," said Albarracín, also the director of the Social Action Lab at Illinois. "This study provides important evidence suggesting that increasing health insurance coverage may play a critical role in curbing the spread of HIV."

The researchers analyzed the effects of the Medicaid expansion using data from 2010-17 on HIV diagnoses per 100,000 population, awareness of HIV status and PrEP use by calculating differences in new diagnoses and PrEP use before and after states adopted the expansions. They compared the differences between treatment counties - that is, all counties in states that expanded Medicaid - versus control counties in states that didn't expand Medicaid.

As access to health insurance and HIV testing improved with the health insurance expansions, a higher percentage of people living with HIV were newly aware of their status, as reflected in rising numbers of HIV diagnoses.

"Although many social factors contribute to rural-urban and other social-health disparities, health insurance accounts for much of the variation in access to care. Hence, expanding health insurance coverage has important implications for HIV prevention and disease transmission," Farkhad said.

"A popular misconception of the ACA" - former President Obama's signature health care law - "is that it's an unwieldy failure of health care policy," Albarracín said. "But our research points to that being false, as the Medicaid expansion prong of 'Obamacare' has been quite successful, providing evidence that expanding access to health insurance is associated with improvements in several HIV-related outcomes. This is clearly one measure that is not a failure in terms of people's lives and health."

Another finding is that the main increase in new HIV diagnoses stems from intravenous drug injection.

"This finding is not surprising given that the U.S. is in the midst of an opioid crisis, and the increase in injection drug use has led to a greater risk of illness due to needle sharing," Farkhad said. "Because there is no evidence that Medicaid expansions affected substance use, the increase in HIV diagnoses attributed to injection is consistent with the improved access to care among those with substance use disorder. Also, people with substance use disorders were more likely to be uninsured prior to the ACA than the general population, which further reinforces the idea that expanding Medicaid is a good thing for public health."

The study has important health policy implications, the researchers said.

"It's a very important lesson in terms of, if you want to eradicate HIV, you're going to have to increase health coverage," Albarracín said. "Otherwise, HIV will continue to spread under the public health radar. The findings about drug use are also important because our team is leading an initiative to prevent HIV infections associated with drug use in 200 counties in Appalachia and the Midwest."

"For COVID-19, public health officials are constantly emphasizing how important it is for people to test, test, test," Farkhad said. "And it's the same idea here. We show how important it is to have insurance coverage to increase testing, and that those extra tests were necessary and have increased the rate of HIV diagnosis.

"It also speaks to the role of access to affordable health care plans. The states that didn't expand Medicaid, especially the Southern states where opioid use is prevalent, have a very high rate of uninsured compared to other states. Expanding insurance coverage to low-income individuals through Medicaid could facilitate HIV prevention and improve HIV-related health outcomes."

Pneumonia and the flu kill tens of thousands of Americans each year, racking up billions of dollars in medical costs and even more in lost productivity.

But new research from the University of Georgia shows that state laws promoting flu vaccinations for hospital workers can substantially reduce the number of influenza-related deaths.

Spanning 23 years, the study looked at the mortality rate from influenza and pneumonia during peak flu season (from December through March of each year), comparing changes in mortality over time in the 13 states and Washington, D.C., that adopted laws to the changes in mortality in states without laws. All states that passed laws require the flu vaccines to be offered to hospital employees. Eleven took it a step further by mandating that workers be vaccinated or required documentation of refusal, with three requiring unvaccinated employees to wear surgical masks during flu season.

The findings align with previous research suggesting that hospital workers may serve as vectors of disease transmission within their hospitals and even in their communities. States that mandated hospital workers receive flu shots saw the biggest reduction in mortality from flu and pneumonia. On average, the adoption of a law promoting vaccination reduced mortality by about two deaths per 100,000 persons, with the reductions primarily occurring among older adult populations.

"The elderly are extremely vulnerable to influenza and are also generally less responsive to the vaccine," said Emily Lawler, corresponding author of the study and an assistant professor in UGA's School of Public and International Affairs. "This study suggests that vaccinating hospital workers against influenza reduces influenza disease transmission and helps protect this vulnerable population."

A federal mandate requiring hospital workers to get an annual flu shot would likely further reduce influenza-related deaths.

This study did not closely examine why some health care workers refuse vaccines. However, if the COVID-19 vaccines are proven to prevent disease transmission--so far they've only been proven to protect the vaccinated individual from disease--then vaccinating hospital workers could be integral to dramatically reducing transmission of COVID-19 and mortality in communities across the country.

"Stricter policies result in higher vaccination rates among health care workers," Lawler said. "Our results are consistent with the idea that these stronger laws result in a larger reduction in influenza-related mortality."

Mandatory vaccinations don't come without some controversy, though. In some cases, health care workers refuse to get vaccinated. It's an issue with the flu shot, which varies in efficacy each year due the limitation of vaccine developers only being able to include several strains of the virus in a given shot. But it's also occurring with the new COVID-19 vaccines at a surprisingly high rate among health care professionals, nursing home workers and other frontline personnel.

SAN ANTONIO and BOSTON - Study findings released Tuesday in the Journal of the American Medical Association (JAMA) hold both good news and bad news about transient ischemic attacks (TIAs), which are harbingers of subsequent strokes.

Sudha Seshadri, MD, professor of neurology at The University of Texas Health Science Center at San Antonio and director of the university's Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, is senior author of the study and senior investigator of the Framingham Heart Study, from which the findings are derived. She said the extensive follow-up of Framingham participants over more than six decades enabled the study to present a more-complete picture of the risk of stroke to patients after a TIA.

The study points to the need for intensive, long-term follow-up of patients who have had a TIA, said lead author Vasileios-Arsenios Lioutas, MD, a neurologist at Beth Israel Deaconess Medical Center and Harvard Medical School.

"According to our findings, people continue to have a high risk of stroke for a sustained time after they've had a TIA," Dr. Lioutas said. "Therefore, one shouldn't think that the high-risk period is just in the first 90 days after the attack and then one can relax. It seems these patients should be followed closely over time, keeping in mind that they are at risk for stroke and paying close attention to controlling their cardiovascular risk factors."

Among 14,059 Framingham participants, 435 had a TIA. Researchers compared the TIA-positive group against a second group of 2,175 participants who did not have a TIA.

People who experienced a TIA had a 4.5- to five-fold higher risk of having a stroke, Dr. Lioutas said. This was the estimate even after taking in to account that patients with TIAs have higher rates of vascular risk factors such as high blood pressure, high cholesterol or diabetes, he said.

The study analyzed three epochs of time, 1948 to 1985, 1986 to 1999, and 2000 to 2017.

"We examined 66 years of follow-up from Framingham participants, which allowed us to study trends over time," Dr. Seshadri said. "We can see that starting in the very early years of the Framingham study, the 1950s, moving on to the most recent times, the risk of subsequent stroke went down a lot."

In the most recent epoch of 2000 to 2017, that risk was significantly lower than in the earlier period from 1948 to 1985. One- and five-year risks of post-TIA stroke in the 2000-2017 epoch were 7.6% and 16.1%, compared to 23.9% and 35.5% during the 1948 to 1985 epoch.

The study didn't set out to show the reason for the improvement, Dr. Seshadri said, but one likely explanation "is that we have gotten better at preventing strokes, we are more aware of the importance of TIAs, and we are doing a better job than in earlier years about stroke prevention."

Dr. Lioutas said it is important for patients who have a TIA to get the same medical workup that stroke patients receive, so that the causes of the TIA can be identified and treated.

Female childhood cancer survivors face a lower likelihood of becoming pregnant than women in the general population, but once pregnant, they are not more likely to undergo an abortion. The findings come from a new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

Cancer survivors might be reluctant to start a family due to concerns for their children's health as well as the potential recurrence of their own cancer. This could lead to a greater likelihood of induced abortions in female survivors who become pregnant.

To examine whether pregnancies of childhood cancer survivors are more likely to end with induced abortions, Johanna M. Melin, MD, PhD, of the Finnish Cancer Registry in Helsinki, Finland, and her colleagues examined data from Finnish registers on cancer, births, and induced abortions.

When the researchers compared 420 first pregnancies of childhood cancer survivors with 2,508 first pregnancies from the general population in 1987 to 2013, survivors had a 28 percent lower probability of becoming pregnant compared with women in the general population, but their risk of a first pregnancy resulting in an induced abortion was similar.

"Our study shows that the risk of terminating a pregnancy is similar in childhood cancer survivors and population controls, suggesting that female childhood cancer survivors are as willing as their peers to continue the pregnancy and become parents," said Dr. Melin. "Also, research has found no increased risk for congenital anomalies in children born to cancer survivors. In our study, termination of pregnancy due to congenital anomaly or birth defect of the fetus was very rare in childhood cancer survivors."

Dr. Melin noted that the reduced probability of pregnancy in childhood cancer survivors seen in this study highlights the persisting need for interventions to preserve patients' fertility during treatment. This supports the American Cancer Society's Preserving Fertility in Female Cancer Patient initiative.

A world-first discovery by researchers at Monash University and The University of Queensland could lead to faster and more effective treatments for chronic health complications, such as cardiovascular disease and cancer, with 'fluorescent' in vivo biosensors.

The research team, led by Dr Simon Corrie from Monash University's Department of Chemical Engineering and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, took an antibody that binds EGFR (epidermal growth factor receptor) proteins and engineered it to monitor the concentration of EGFR proteins in serum solutions over time.

Co-authors of the paper, published in ACS Sensors, are Dr Christian Fercher, Dr Martina Jones and Professor Stephen Mahler from The University of Queensland and the Australian Institute for Bioengineering and Nanotechnology.

An inability to detect the growth of EGFR proteins in humans can be associated with the development of a number of tumours, including cancer, as well as the onset of diseases like Alzheimer's.

Using an independent detection mechanism developed by the research team, involving fluorescent dyes, researchers created a biosensor from a well-known antibody that was able to 'read out' changes of the EGFR protein in real-time by monitoring detectable changes in the fluorescence spectra.

The ability to monitor protein biomarker concentrations in body fluids in real-time is invaluable for tracking patients at risk of rapid deterioration, including those requiring personalised drug monitoring or those at high risk of complications arising from critical conditions, like sepsis, heart attack or tumour response to treatment.

No one has been able to engineer an antibody for continuous testing until now.

"All the diagnostic tests that we are familiar with involve sampling something (blood, urine, tissue) at a particular point in time and taking the same to a lab to interrogate it. But for patients suffering from acute conditions, in which time to diagnose and rapid treatment are very important, this traditional diagnostic process is not good enough," Dr Corrie said.

"Monitoring dynamic changes in proteins, for example protein levels increasing or decreasing over time, is likely to provide much more detailed information about a disease or treatment process, but the sensors required to do this don't exist outside of continuous glucose testing for diabetes.

"Our capacity to create antibodies, which bind reversibly to targets and can be 'read out' using fluorescence, means we can develop in vivo sensors. These sensors can monitor the levels of critical biomarkers as they change over time in response to a disease or treatment, rather than just sending a sample to a lab and getting a snapshot in a day or two.

"These biomarkers could include the amount of surface proteins on a cancer cell and whether or not a drug causes them to reduce in size, therefore testing the efficacy of treatment. It can also be used to monitor the concentration of potentially toxic drugs, like some antibiotics."

This discovery was able to engineer an antibody fragment capable of reversibly binding to a protein analyte (scFv) in a chemical solution, while retaining the specificity of the original antibody sequence.

Through their efforts, continuous in vitro monitoring over multiple hours was successfully recorded.

"Work is underway to employ dyes that are much better suited to medical applications," Dr Corrie said.

"In future, we expect that this process will be used to generate a range of biosensors that can monitor protein concentration continuously inside the human body, through a biopharmaceutical process, or in the environment."

Special immune cells found in the brain, microglia, play a key role in the processes that make you feel uneasy and depressed in correlation with inflammation. This is the conclusion of a study using mice carried out by researchers at Linköping University, Sweden. The results have been published in the scientific journal Immunity, and suggest that microglial cells contribute to the negative mood experienced during several neurological diseases, and maybe also depression.

David Engblom's research group at Linköping University has spent many years looking at why inflammation in the body, such as a common cold or influenza, causes us to feel poorly and despondent, and why we feel like retiring into our shell. The activity of the immune system influences nerve cells in some way. However, normal cells of the immune system are not able to get into the brain: it is sensitive and must be protected. Instead, the brain has its own special immune cells: microglial cells.

Previous research has shown that microglial cells are activated in several neurological diseases, such as Alzheimer's disease, Parkinson's disease and stroke. People who are affected by these conditions also often fall into a negative mood. Other previous research has suggested that inflammatory processes also play a role in the development of depression. This led the researchers behind the new study to examine more closely whether microglial cells are involved in regulating mood during inflammation.

"The study showed that animals feel sick and uneasy when we activate the microglial cells. We demonstrate that two signal molecules, interleukin-6 and prostaglandin E2, are particularly important in these processes. It's not surprising that these signal substances are central, but we were a bit surprised that it is the microglial cells that release these molecules", says David Engblom, professor in the Department of Biomedical and Clinical Sciences (BKV) at Linköping University.

During inflammation, many processes are initiated in several cell types. One of the challenges in determining the role played by a specific cell type in the body, therefore, is to isolate its effects. In this study, the scientists used a technique known as chemogenetics, which enabled them to switch on the activity specifically in microglial cells in mice. The researchers activated the microglial cells when the mice were being kept in a certain type of surroundings. The mice subsequently avoided this type of surroundings, which the researchers interpret as showing that the animals disliked the experience. The mice also became less interested in a sweet solution, which they normally find very tempting.

In order to investigate whether the microglial cells are an important link between the immune system and mood, the researchers investigated what happened when microglial cells are inhibited. When the microglial cells were not available for activation, the mice did not feel poorly, even when they had inflammation. This reinforces the idea that these cells are necessary for the process.

"Our results show that the activation of microglial cells is sufficient to create aversion and negative mood in mice. It's natural to suggest that similar processes take place in several human diseases. It's not unlikely that activated microglia contribute to the discomfort and depressed mood in people with inflammatory and neurological diseases", says David Engblom.

If further research demonstrates that the biological mechanism described in the study functions in the same way in humans, it may be possible in the long run to reduce symptoms of depression by inhibiting this mechanism.

New Orleans, LA - An analysis by Nicholas Gilpin, PhD, Professor of Physiology and Associate Director of the Alcohol and Drug Abuse Center of Excellence at LSU Health New Orleans School of Medicine, and Michael Taffe, PhD, Professor of Psychiatry at the University of California San Diego, summarizes long-standing racial inequities in federal funding for biosciences research from the National Institutes of Health (NIH). Their report describes prior failures to correct these racial inequities and offers strategies that may be effective in eliminating these disparities. Their paper, published online in the open-access science journal, eLife, is available for download here.

"There is structural racism at all levels of the biomedical research enterprise," notes Dr. Gilpin, who is also Vice-Chair of Research in Physiology at LSU Health New Orleans. "One of the most overt examples of this is in the fact that white scientists are 1.7 times more likely to receive federal research grants than Black scientists, even when controlling for a long list of potential mediating variables. This disparity was reported in 2011, and in 2019 it was confirmed that nothing has changed during the last decade."

The authors describe the impact that racial disparities in federal funding rates have on both biomedical scientists of color and the field at large. They also issue a call to action to leaders at the National Institutes of Health (NIH) and universities, grant reviewers, tenured faculty, and search and tenure committee members.

"Put simply, this is unacceptable," adds Dr. Gilpin. "The NIH must acknowledge its own systemic and structural racism and must take action to eliminate it. This action must be demanded by all scientists, but especially by those that are NOT adversely affected by the policy, that is, by scientists that are white, tenured, and in leadership positions."

The authors maintain that federal research dollars are the primary form of "career currency" in academic research, and that racial disparities in federal funding have many negative trickle-down effects on the careers of Black scientists and the biomedical sciences at-large. The authors evaluate current approaches to address the problem and show why these strategies are unlikely to achieve success on their own. They recommend adding additional strategies that include increased data transparency, using paylines to reduce disparities and employing a top-down approach previously used to help early-stage investigators in the biomedical sciences.

"The United States is having a reckoning with the pervasive and oppressive structural racism that permeates nearly all of its institutions," Dr. Gilpin concludes. "Although this has been going on for centuries, this seems like a bellwether moment in our society because these ideas have entered the collective consciousness and mobilized sections of U.S. society that previously stayed on the sidelines."

Although progress has been made to increase the participation of historically underrepresented groups in biomedical training stages, the National Institutes of Health acknowledges that members of these groups are still less likely to be hired as independently funded faculty researchers. To address that need, in December, the NIH announced two new funding opportunities that will provide support to institutions to recruit diverse groups of early-stage research faculty and prepare them to thrive as NIH-funded researchers.

Research by an international team of medical experts has found cancer patients could be up to four times more likely to die following cancer surgery in low to lower-middle income countries than in high-income countries. It also revealed lower-income countries are less likely to have post-operative care infrastructure and oncology services.

The global observational study, published in The Lancet, explored global variation in post-operative complications and deaths following surgery for three common cancers. It was conducted by researchers from the GlobalSurg Collaborative and NIHR Global Health Unit on Global Surgery - led by the University of Edinburgh, with analysis and support from the University of Southampton.

Between April 2018 and January 2019, researchers enrolled 15,958 patients from 428 hospitals in 82 countries undergoing surgery for breast, colorectal or gastric cancer. This included a mix of patients from high-income countries, upper middle-income countries and low/lower middle-income countries. 53 percent (8,406) of patients underwent surgery for breast cancer, 39 percent (6,215) for colorectal cancer, and 8 percent (1,337) for gastric cancer. The authors analysed how common death or major complications were within 30 days of surgery.

Deaths among gastric cancer patients were more than three times higher in low/lower middle-income countries (33 deaths among 326 patients, 3.72 odds of death) than high-income countries (27 deaths among 702 patients).

Patients with colorectal cancer in low/lower middle-income countries were also more than four times more likely to die (63 deaths among 905 patients, 4.59 odds of death), compared with those in high-income countries (94 deaths among 4,142 patients). Those in upper middle-income countries were two times as likely to die (47 deaths among 1,102 patients, 2.06 odds of death) as patients in high-income countries.

No difference in 30-day mortality was seen following breast cancer surgery.

Similar rates of complications following surgery were observed in patients across all income groups, however those in low/lower middle-income countries were six times more likely to die within 30 days of a major complication (96 deaths among 133 patients, 6.15 odds of death), compared with patients in high-income countries (121 deaths among 693 patients). Patients in upper middle-countries were almost four times as likely to die (58 deaths among 151 patients, 3.89 odds of death) as those in high-income countries.

Patients in upper middle-income and low/lower middle-income countries tended to present with more advanced disease compared with those in high-income countries, however researchers found that cancer stage alone explained little of the variation in mortality or post-operative complications.

Assessing hospital facilities and practices across the different income groups revealed that hospitals in upper middle-income and low/lower middle-income countries were less likely to have post-operative care infrastructure (such as designated post-operative recovery areas and consistently available critical care facilities) and cancer care pathways (such as oncology services).

Further analysis revealed that the absence of post-operative care infrastructure was associated with more deaths in low/lower middle-income countries (7 to 10 more deaths per 100 major complications) and upper middle-income countries (5 to 8 more deaths per 100 major complications).

Academic lead at the University of Southampton and member of GlobalSurg, Mr Malcolm West, commented: "It was a great privilege for me to contribute to this landmark study. Failure to rescue from death after post-operative complications is of global importance. As a colorectal surgeon, it is disconcerting to see that patients in LMIC present with more advanced cancers compared to high-income countries. Interestingly, advanced cancer rates alone did not fully explain the high death and complication rates we have seen.

"An urgent focus on improving global healthcare systems, especially in LMIC, to detect and intervene when complications occur would help save lives following cancer surgery."

Professor Ewen Harrison, of the University of Edinburgh, said: "Our study is the first to provide in-depth data globally on complications and deaths in patients within 30 days of cancer surgery. The association between having post-operative care and lower mortality rates following major complications indicates that improving care systems to detect and intervene when complications occur could help reduce deaths following cancer surgery."

The authors acknowledge some limitations to their study. Researchers only looked at early outcomes following surgery, but, in future, they will study longer-term outcomes and other cancers. Outcomes can be poorly captured and understood in settings with limited resources, which will have affected the team's findings on the effectiveness of surgery. Further detailed analysis is needed to provide more robust evidence regarding associations between patient outcomes and hospital facilities.

PHILADELPHIA (January 25, 2021) - While eating less and moving more are the basics of weight control and obesity treatment, finding ways to help people adhere to a weight-loss regimen is more complicated. Understanding what features make a diet easier or more challenging to follow can help optimize and tailor dietary approaches for obesity treatment.

A new paper from the University of Pennsylvania School of Nursing (Penn Nursing) analyzed different dietary approaches and clinical trials to better understand how to optimize adherence and subsequent weight reduction. The findings have been published in the Journal of Clinical Investigation.

"There is not convincing evidence that one diet is universally easier to adhere to than another for extended periods, a feature necessary for long-term weight management," says Ariana M. Chao, PhD, CRNP, Assistant Professor of Nursing at Penn Nursing and lead investigator of the paper. "Progress in improving dietary adherence could result from greater efforts to examine mechanisms underlying interindividual variability in responses to dietary approaches. The more we understand the characteristics of individuals who are trying to lose weight, the more able we may be to identify dietary interventions that facilitate their efforts."

The article detailing the study, "Dietary Interventions for Obesity: Clinical and Mechanistic Findings," is available online. Co-authors of the article include Kerry M. Quigley and Thomas A. Wadden, both of the Perelman School of Medicine at the University of Pennsylvania.

Data demonstrate ADG2 binds to all known variants of SARS-CoV-2 and is not impacted by known circulating resistance mutations-

Company expects to begin clinical studies for a half-life extended version of ADG2 for the treatment and prevention of COVID-19 in early 2021-

Waltham, MA - January 25, 2021- Adagio Therapeutics, Inc., a biotechnology company developing best-in-class antibodies to broadly neutralize coronaviruses, today published in vitro and in vivo data in Science on its lead antibody candidate, ADG2, which demonstrated similar or higher potency against SARS-CoV-2 compared to other monoclonal antibodies (mAbs) in clinical development and strong binding to all known SARS-CoV-2 variants. Uniquely, ADG2 also showed broad and potent neutralization against a range of sarbecoviruses that pose a threat to humans and protective efficacy in murine models of SARS and COVID-19. The data show that ADG2 effectively binds to and has the potential to protect against common circulating SARS-CoV-2 variants as well as future SARS-related viruses with pandemic potential. Adagio's half-life engineered version of ADG2, called ADG20, could offer protection against COVID-19 for up to a year. Adagio expects ADG20 to enter Phase 1 clinical studies in early 2021.

"These studies demonstrate our lead antibody shows comparable or higher neutralization potency against SARS-CoV-2 than leading antibodies currently in development for COVID-19 and binds effectively to all of the most commonly circulating SARS-CoV-2 variants, indicating that it should not be affected by known resistance mutations. Unlike most antibodies currently in clinical development or approved for emergency use, ADG20 binds to a highly conserved epitope, so we believe it will also be effective against future emerging SARS-CoV-2 strains and related pre-emergent sarbecoviruses," said Laura Walker, Ph.D., chief scientific officer of Adagio.

Data highlights:

Potency and breadth of coverage

ADG2 (the precursor to ADG20) provided complete protection against severe SARS-CoV-2 and SARS-CoV disease in murine models of COVID-19 and SARS, respectively.

When compared to other mAbs in development or approved for emergency use, ADG2 showed similar or higher potency against SARS-CoV-2 in two authentic neutralization assays.

ADG20 demonstrated strong binding to all commonly circulating SARS-CoV-2 variants.

ADG2 also showed broad and potent neutralizing activity against SARS-CoV and two SARS-related coronaviruses currently known to be circulating in bat populations (WIV-1 and SHC014).

The epitope targeted by ADG2 is highly conserved across clade 1 sarbecoviruses, and ADG2 binds with high affinity to a large panel of clade I sarbecovirus receptor binding domains (RBDs).

Viral resistance variants

ADG2 binds with high affinity to more than 30 of the most frequently observed SARS-CoV-2 RBD variants reported in the GISAID database, including the known variants resistant to other monoclonal antibodies in development or approved for emergency use.

Notably, no mutations have been reported at key ADG20 contact residues in full length viral genomic sequences (>152,000) of SARS-CoV-2 included in the GISAID database as of December 9, 2020, suggesting a low risk of pre-existing resistance to ADG20 in the clinic.

Other enhanced attributes

In vitro engineering of ADG2 avoided many of the common pitfalls associated with monoclonal antibody enhancements. Specifically, ADG2 demonstrated favorable biophysical properties in a series of in vitro assays that have been shown to be predictive of downstream behaviors such as serum half-life, ease of manufacturing, ability to formulate to high concentrations, and long-term stability.

Although not included in the pre-publication, Adagio also engineered ADG2 to extend serum half-life and enhance mucosal localization.

"As we look to the future, it is clear we will need potent treatment and prevention for not only COVID-19 but also for future coronaviruses, which we can now say with near certainty will continue to emerge," said Tillman Gerngross, Ph.D., chief executive officer of Adagio. "Based on these data, we believe ADG20 has the potential to offer unsurpassed treatment and prevention for COVID-19 while serving as a potent and broadly protective countermeasure to protect against resistant strains of SARS-CoV-2 as well as future sarbecovirus threats. Importantly, we took our time to develop ADG20 without sacrificing duration of effect, manufacturability, and affordability. We look forward to advancing ADG20 into the clinic in early 2021 to learn how it may provide protection from the greatest pandemic of our lifetime."

Working in preclinical models, researchers report that plitidepsin, a drug with limited clinical approval for the treatment of multiple myeloma, is more potent against SARS-CoV-2 than remdesivir, an antiviral that received FDA emergency use authorization for the treatment of COVID-19 in 2020. The results suggest plitidepsin should be further evaluated as a COVID-19 therapy, the authors say; because it targets a host protein rather than a viral protein, if treatment proves successful in humans, the SARS-CoV-2 virus won't be easily able to gain resistance against the drug through mutation. The ongoing SARS-CoV-2 pandemic has created the need for antiviral therapeutics that can be swiftly moved into the clinic. This has led researchers to screen clinically approved antivirals. While traditional antivirals, like remdesivir, target viral enzymes that are often subject to mutation, and thus to the development of drug resistance, antivirals that target the cell host proteins required for viral replication could avoid resistance. In earlier work investigating host proteins likely to play a role in the viral life cycle of SARS-CoV-2, including a study in Science in October 2020, Kris White and colleagues found that targeting the host translation machinery that is used in the replication of many viral pathogens could greatly inhibit SARS-CoV-2. Based on this they evaluated plitidepsin, a known inhibitor of a protein involved in host protein translation. In addition to having a limited clinical approval for treating multiple myeloma, it has also successfully completed a phase I/II clinical study for the treatment of COVID-19. Here, in studies in human cells, plitidepsin demonstrated potent anti-SARS-CoV-2 activity - 27.5-fold more so than remdesivir as tested in the same cell line. In a model of human lung cells, plitidepsin greatly reduced viral replication. After further experiments involving remdesivir and plitidepsin in vitro, the researchers suggest that plitidepsin has an additive effect with this approved drug and would be a potential candidate for a combined therapy. The researchers also tested the drug in mice later infected with SARS-CoV-2. Mice who received the drug prophylactically had reduced viral load and lung inflammation compared to control mice. "We believe that our data and the initial positive results from PharmaMar's clinical trial suggests that plitidepsin should be strongly considered for expanded clinical trials for the treatment of COVID-19," conclude the authors.