Body

New research found that, compared with a father's traits related to allergies and asthma, a mother's traits create a higher risk that a child will develop these same traits in early childhood. By the time the children were 6 years old, however, both parents presented the same risk. This suggests that non-genetic factors related to mothers--such as factors present in the uterus during pregnancy--may confer an added risk of allergies and asthma to children.

The Clinical & Experimental Allergy study included 685 parent-child trios.

"This study adds to the increasing evidence linking the pregnancy period to disease in early childhood. We find this discovery very interesting, as it circumvents any known or unknown genetic factors that could add to the heritability of asthma and allergies," said senior author Hans Bisgaard, MD, DMSc, of the University of Copenhagen, in Denmark.

In one of the first studies addressing the role of sex hormones' impact on stem cells in the gut, scientists outline new insights showing how a steroidal sex hormone, that is structurally and functionally similar to human steroid hormones, drastically alters the way intestinal stem cells behave, ultimately affecting the overarching structure and function of this critical organ. The authors found that ecdysone, a steroid hormone produced by fruit flies, stimulates intestinal stem cell growth and causes the gut of the female fruit fly to grow in size, and induces other critical changes. The study also provides a mechanism to account for sex-specific roles for intestinal stem cells in normal gut function. Moreover, the research presents evidence that gut hormones may accelerate tumor development. The findings, reported jointly by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) and the German Cancer Research Center (DKFZ), are published today in the journal Nature.

Bruce Edgar, PhD, a stem cell biologist at HCI and professor of oncological sciences at the U of U, together with Aurelio Teleman, PhD, division head at DKFZ and professor at Heidelberg University jointly led the work. They asked whether sex hormones affect intestinal stem cells' ability to multiply and contribute to gut growth. "My lab and many others around the world have studied the Drosophila gut for some time to better understand how stem cells are regulated," says Edgar. "We knew that male and female fruit flies exhibited differences in their intestine - for example, the female's intestine is larger than the male's, and females develop intestinal tumors much more readily than males - but we didn't know why." This study adds significant insights into these differences, and how they arise.

The Edgar and Teleman teams found that ecdysone, a sex-specific hormone, can drastically alter the growth properties of stem cells in an organ that, remarkably, is not directly involved in reproduction. They found that these changes affect the structure and function of the entire organ. They discovered that subjecting male flies to ecdysone caused their otherwise slow dividing stem cells to divide as fast as in females, leading to intestinal growth in males as well. This suggests that the limiting difference between the division of stem cells in male and female flies is the circulating levels of the hormone.

This process confers both advantages and disadvantages to the female fruit fly during the course of its life. Initially, more ecdysone in females helps with the evolutionarily critical processes of reproduction. It promotes gut enlargement, facilitating nutrient absorption, which helps the fly lay more eggs. But later in life, the ecdysone hormone, produced by the ovaries, eventually causes gut disfunction that can shorten the lifespan in female fruit flies by creating an environment that favors tumor growth. While humans don't produce ecdysone, they do have related steroid hormones such as estrogen, progesterone and testosterone, which have similar mechanisms of action.

The experimental work on this study was performed primarily by Sara Ahmed, a joint PhD student between the Edgar and Teleman labs at the Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) and the DKFZ. Ahmed designed experiments utilizing various genetic tools to switch genes on and off in different cell types in the fly's intestine and in its ovaries, which produce ecdysone. "Our study provides conclusive evidence that sex hormones alter the behavior of non-sex organs like the intestine," says Ahmed. She further speculates that long-term implications of this research may include exploration of new paths to treating human cancers.

According to the researchers, understanding whether a similar stem cell-hormone relationship operates in human organs will require further studies. They plan to explore this in the future. In addition to the critical role played by sex hormones in intestinal stem cell behavior, the authors believe this study in Drosophila potentially unveils a new mechanism that may play out in human physiology and pathology. Insights from this study add to a growing body of work showing that the incidence cancers of non-reproductive organs, including colon and gastric cancers, are different in males and females.

Oncotarget Volume 11, Issue 27 published "Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer" by Genet et al. which reported that this study aimed to develop a hemolysis correction equation and evaluate its role in small-cell lung cancer (SCLC) diagnostics.

A hemolysis correction equation was obtained by analyzing the relationship between the measured Neuron-specific enolase (NSE) concentration and the degree of hemolysis.

Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.

Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations.

Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

Dr. Daan van de Kerkhof from The Catharina Hospital Eindhoven as well as The Máxima Medical Center said, "Neuron-specific enolase (NSE) is a dimeric metalloenzyme which functions as a cell specific isoenzyme of the glycolytic enzyme enolase."

Furthermore, improved discrimination of the two main lung cancer subtypes, SCLC and non-small cell lung cancer was achieved when applying a diagnostic cut-off value of 25 ng/mL NSE or analyzing multiple protein tumor markers such as NSE and progastrin-releasing peptide at the same time.

Considering the use of NSE in lung cancer diagnostics and the medical actions that may follow, accurate and reliable quantification of NSE is of main importance.

However, previous studies evaluating the prognostic value of NSE in lung cancer diagnostics did not apply exclusion criteria or did not include the effect of hemolysis on the measured NSE concentration as such, while other factors that could influence serum tumor marker concentrations were addressed.

Therefore, this study aimed to develop, validate and apply a hemolysis correction equation that nullifies the effect of hemolysis on NSE quantification in samples of adult patients.

Using this equation, the effect of hemolysis correction on the NSE cut-off value in SCLC diagnostics was evaluated and the maximum acceptable degree of hemolysis for reliable correction was established.

"The effect of hemolysis correction on the NSE cut-off value in SCLC diagnostics was evaluated and the maximum acceptable degree of hemolysis for reliable correction was established."

The Kerkhof Research Team concluded in their Oncotarget Research Paper, "this study demonstrates that a hemolysis correction equation improves diagnostic accuracy of serum NSE concentrations in patients suspected of lung cancer. A hemolysis correction equation is therefore suggested to be incorporated in NSE-based clinical decision making, bearing in mind that results of samples with an H-index above 30 μmol/L should not be reported to clinicians."

A ringing bell vibrates simultaneously at a low-pitched fundamental tone and at many higher-pitched overtones, producing a pleasant musical sound. A recent study, just published in the Journal of the Atmospheric Sciences by scientists at Kyoto University and the University of Hawai'i at Mānoa, shows that the Earth's entire atmosphere vibrates in an analogous manner, in a striking confirmation of theories developed by physicists over the last two centuries.  

In the case of the atmosphere, the "music" comes not as a sound we could hear, but in the form of large-scale waves of atmospheric pressure spanning the globe and traveling around the equator, some moving east-to-west and others west-to-east. Each of these waves is a resonant vibration of the global atmosphere, analogous to one of the resonant pitches of a bell. The basic understanding of these atmospheric resonances began with seminal insights at the beginning of the 19th century by one of history's greatest scientists, the French physicist and mathematician Pierre-Simon Laplace. Research by physicists over the subsequent two centuries refined the theory and led to detailed predictions of the wave frequencies that should be present in the atmosphere. However, the actual detection of such waves in the real world has lagged behind the theory.

Now in a new study by Takatoshi Sakazaki, an assistant professor at the Kyoto University Graduate School of Science, and Kevin Hamilton, an Emeritus Professor in the Department of Atmospheric Sciences and the International Pacific Research Center at the University of Hawai?i at Mānoa, the authors present a detailed analysis of observed atmospheric pressure over the globe every hour for 38 years. The results clearly revealed the presence of dozens of the predicted wave modes.

The study focused particularly on waves with periods between 2 hours and 33 hours which travel horizontally through the atmosphere, moving around the globe at great speeds (exceeding 700 miles per hour). This sets up a characteristic "chequerboard" pattern of high and low pressure associated with these waves as they propagate (see figure).

"For these rapidly moving wave modes, our observed frequencies and global patterns match those theoretically predicted very well," stated lead author Sakazaki. "It is exciting to see the vision of Laplace and other pioneering physicists so completely validated after two centuries."

But this discovery does not mean their work is done.

"Our identification of so many modes in real data shows that the atmosphere is indeed ringing like a bell," commented co-author Hamilton. "This finally resolves a longstanding and classic issue in atmospheric science, but it also opens a new avenue of research to understand both the processes that excite the waves and the processes that act to damp the waves."

So let the atmospheric music play on!

New research published in the journal BMJ Open Sport and Exercise Medicine indicates that men and younger adults have been less physically active during the COVID-19 lockdown.

The study, led by Anglia Ruskin University (ARU) and Ulster University, includes data from 911 UK adults who took part in an online survey which began on 17 March.

The research found that 75% of UK adults met the World Health Organisation's physical activity recommendations of 150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week, since the introduction of social distancing regulations.

This is higher than previous studies carried out before the COVID-19 pandemic, which found that between 58% and 66% of the UK adult population typically meet physical activity guidelines

The new study found that women, older adults, and those with a higher annual household income were significantly more likely to meet the WHO's physical activity guidelines. This is the opposite of studies carried out prior to the pandemic, where men and younger adults were found to have higher levels of physical activity.

Lead author Dr Lee Smith, Reader in Physical Activity and Public Health at Anglia Ruskin University (ARU), said: "The overall levels of physical activity are higher than we were expecting.

"It may be that the UK public have experienced an increase in free time and used this time to be physically active. Additionally, during the early stages of the outbreak, one of the few reasons to leave home was to take part in an hour of exercise. As well as offering a reason to go outside, this may have served as a target for some people.

"Typically, the proportion of UK adults meeting physical activity guidelines declines with age. Therefore, there should be additional support offered to older adults to encourage them to sustain this level of physical activity post pandemic."

Study after study has shown that statins can prevent heart attacks, strokes and death in middle-aged adults. But in 28 major clinical trials of statins, only 2 percent of participants have been 75 years or older. This means that even though older adults are at greater risk of heart disease and death, there is scant data on whether statins should be prescribed for them. A new study led by investigators from Brigham and Women's Hospital and VA Boston Healthcare System leverages national data from the U.S. Veterans Health Administration Services and Centers for Medicare & Medicaid Services to shed new light on the role statins may play for older adults who have not yet experienced a heart attack, stroke or other cardiovascular event. In their retrospective analysis, the researchers found that the risk of dying from any cause was lower by 25 percent among veterans who were using statins compared to those who were not treated with statins. The risk of dying from a cardiovascular event, such as a heart attack or stroke, was lower by 20 percent. The team's results are published in JAMA.

"Based on these data, age is not a reason to not prescribe statins," said lead and corresponding author Ariela Orkaby, MD, MPH, a physician scientist at VA Boston Health Care System and in the Division of Aging at the Brigham . "Statins are commonly studied and prescribed for middle-aged adults but understudied in people over age 75. One of the most remarkable things about our results is that we found the benefit of statins held true regardless of whether a person was older or younger or had a condition such as dementia."

Orkaby and colleagues looked at data on veterans who used VA services between 2002 and 2012, were 75 years or older, and had not previously had a heart attack, stroke or other cardiovascular event. Of the more than 300,000 eligible veterans, the team identified more than 57,000 who began taking statins during this time. Using propensity scoring, the authors compared individuals who began taking statins to those who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for the drug.

Overall, taking statins was significantly associated with lower risk of death from a cardiovascular event or death from any cause. And the benefits remained for veterans at advanced age, including those who were 90 years or older. Lower death rates extended to those with other conditions such as dementia -- individuals who have been excluded from previous studies. In secondary analyses, the team found that starting a statin was also significantly associated with a lower risk of cardiovascular events such as heart attacks and strokes. Orkaby notes that it was particularly intriguing to see a marked decline in rate of strokes among the study's black participants.

"There are many interesting leads to follow up on," said Orkaby, "but it's important to keep in mind that this is not a randomized, clinical trial. Instead, it's a retrospective analysis using real world data that helps us explore where the truth lies."

The study focused only on veterans, a predominantly white and male population, which may limit its generalizability, but the study's size made it possible to glean statistically meaningful information on underrepresented groups. During the study's timeframe, the most commonly prescribed statin was simvastatin, but currently, higher-dose and higher-intensity statins have become more frequently prescribed. While statins are generally well tolerated, many people report aches and pains as a side effect, which may lead some to stop taking the drug. The current study did not evaluate whether patients discontinued statin use.

Two randomized, clinical trials of statins among older adults are now underway with results from one of the studies expected later this year. Orkaby and colleagues plan to follow up on their study by exploring the effects of statin dosing and examining outcomes for sub-populations included in their analysis.

DURHAM, N.C. - Researchers from the HIV Prevention Trials Network (HPTN) announced today that the HPTN 083 clinical trial showed that a pre-exposure prophylaxis (PrEP) regimen containing long-acting cabotegravir (CAB LA) injected once every 8 weeks was superior to daily oral tenofovir/emtricitabine (TDF/FTC) for HIV prevention among cisgender men and transgender women who have sex with men. The results were reported at the 23rd International AIDS Conference (AIDS 2020: Virtual). HPTN 083 is a randomized, controlled, double-blind study comparing the safety and efficacy of a regimen including CAB LA to daily TDF/FTC at 43 sites around the world.

An independent Data and Safety Monitoring Board (DSMB) that reviewed interim study data in May 2020 found that the PrEP regimen including CAB LA injected once every 8 weeks safely and effectively prevented HIV acquisition in the study population. Consequently, the DSMB recommended stopping the blinded comparison, offering CAB to all study participants, and disseminating the results. The final analysis of these data demonstrates the superiority of CAB compared to TDF/FTC for PrEP in the HPTN 083 study population.

"The HPTN 083 results demonstrating the superiority of CAB to TDF/FTC have the potential to transform the landscape of HIV prevention for cisgender MSM and transgender women," said HPTN 083 protocol chair Dr. Raphael J. Landovitz. "We know that some people have difficulty with or prefer not to take pills, and an injectable product such as long-acting CAB could be a very important option for them. We want to thank the study participants and research staff, as this study would not have been possible without their dedication and commitment." Dr. Landovitz is a professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and co-director of the UCLA Center for Clinical AIDS Research & Education (CARE).

Overall, HPTN 083 enrolled 4,570 cisgender men and transgender women who have sex with men at research sites in Argentina, Brazil, Peru, South Africa, Thailand, the U.S., and Vietnam. Two-thirds of study participants were under 30 years of age, and 12% were transgender women. Half of the participants in the United States identified as Black or African American.

A total of 52 HIV infections occurred during follow-up, with 13 infections in the CAB arm (incidence rate 0.41%) and 39 infections in the TDF/FTC arm (incidence rate 1.22%). The hazard ratio in the CAB versus TDF/FTC arms was 0.34 (95% CI 0.18-0.62), corresponding to a 66% reduction in incident HIV infections in study participants given CAB compared to TDF/FTC. These results meet the statistical criteria for superiority of the regimen containing CAB compared to TDF/FTC in the HPTN 083 study population. The consistent adherence to TDF/FTC throughout the study and low incidence rate in both arms of the study clearly demonstrates both agents were effective at preventing HIV acquisition.

"Adding long-acting injectable CAB to the HIV prevention toolbox could go a long to lowering HIV incidence among cisgender men and transgender women who have sex with men worldwide and, eventually, toward ending the epidemic," said HPTN 083 protocol co-chair Dr. Beatriz Grinsztejn, director of the Instituto de Pesquisa Clinica Evandro Chagas HIV/AIDS Clinical Research Centre of the Oswaldo Cruz Foundation-Fiocruz in Rio de Janeiro.

"It is heartening that HPTN 083 showed that both the regimen containing CAB and oral TDF/FTC demonstrated high efficacy for prevention of HIV acquisition in the study, offering people options that best fit their lifestyle," said Dr. Myron Cohen, HPTN co-principal investigator and director of the Institute for Global Health at the University of North Carolina in Chapel Hill.

An ongoing study, HPTN 084, is comparing the safety and efficacy of CAB LA to oral TDF/FTC for PrEP among cisgender women in sub-Saharan Africa. This study began approximately a year after the launch of HPTN 083 and was also reviewed in May 2020 by the DSMB, which recommended that the study continue as planned.

"We look forward to the results from HPTN 084, a critically important sister study among women at risk for HIV in sub-Saharan Africa," said Dr. Wafaa El-Sadr, HPTN co-principal investigator, director of ICAP and professor of epidemiology and medicine at Columbia University in New York. "Offering various HIV prevention options to women is critically important for control of the global HIV epidemic."

Interstitial lung diseases (ILDs) are a common and serious consequence of rheumatoid arthritis (RA). The prevalence varies depending on population and diagnostic method, but at least 5 to 10 percent of all RA patients suffer from this condition, which leads to inflammatory changes in lung tissue and pulmonary alveoli. It is accompanied by a dry cough and breathing difficulties. A severe course may lead to scarring of lung tissue, which is referred to as lung fibrosis. This may lead to a life-long dependency on oxygen supply or even a lung transplant. "In approximately 10 to 20 percent of all RA patients, lung disease is the cause of premature death1", explains EULAR President Professor Dr. med. Iain B. McInnes from The University of Glasgow, Scotland, Great Britain. "Particularly in these times when we are concerned about respiratory infections, the reduction of additional risk factors for lung damage of rheumatoid arthritis patients must be evaluated."

For this reason, rheumatologists welcome the results of two new studies indicating that the immunosuppressant Methotrexate, which can provoke an acute lung condition (acute pneumonitis), does not appear to be an additional risk factor for chronic interstitial lung diseases in RA patients. In previous years, it was suspected that this immunosuppressant may increase the risk for RA-associated chronic ILD.

"RA patients have a higher risk of suffering from interstitial lung disease than the general population. However, based on our large dataset, there is no evidential correlation to the treatment with Methotrexate," explains Professor Dr. Lene Dreyer from Aalborg University in Denmark, summarising the results of her current cohort study. Dr. Dreyer's research refers to patient data from the Danish National patient registry as well as the DANBIO registry for rheumatic conditions. In cooperation with the team of researcher Else Helene Ibfelt from the Steno Diabetes Center Copenhagen, Denmark, she examined a total of 30,512 RA patients registered there between 1997 and 2015 for ILD and breathing conditions, taking into account their respective medication.

A current case control study also examining the connection between treatment with MTX and lung diseases in France came to the same conclusion. "In a total of 1,223 RA patients, we were not only able to show that MTX has no impact on the development of interstitial lung diseases but, in fact, may contribute to delaying this development," summarises the author Dr. Pierre-Antoine Juge from Bichat-Claude Bernard Hospital in Paris, France. The number of RA patients affected by ILD therapy was reduced by more than half in comparison with RA patients not receiving any MTX treatment."

"Of course, further examinations are required to support the results and assure patients and physicians that treatment with MTX does not have any negative impact on the pulmonary health of patients suffering from rheumatoid arthritis," explains Professor Dr. John Isaacs, EULAR Scientific Chair, The University of Newcastle, Great Britain. Currently there are very few effective treatments for interstitial lung disease, increasing the importance of these results, which may even suggest methotrexate as a potential therapy. But, notwithstanding these data in relation to RA-associated ILD, it remains important to remember that MTX can cause an acute pneumonitis.

Due to the still existing general risk for ILD, experts recommend examining RA patients regularly for any pulmonary changes to enable timely treatment-particularly in times of the COVID-19 pandemic. In case of any suspicion of ILD, the degree of reduction in pulmonary function can be determined by means of functional examinations of the lung. ILD can also be diagnosed by means of medical imaging such as computer tomography or bronchoscopy.

WHAT:
A pre-exposure prophylaxis (PrEP) regimen containing an investigational long-acting form of the HIV drug cabotegravir injected once every 8 weeks was more effective than daily oral Truvada at preventing HIV acquisition among cisgender men who have sex with men and transgender women who have sex with men in a clinical trial sponsored by the National Institutes of Health. While both methods were highly effective for HIV prevention in the study population, the final data analysis indicated that cabotegravir had a superior protective effect. Findings from the Phase 2b/3 study, called HPTN 083, will be discussed in an online press conference and oral presentations during the 23rd International AIDS Conference (AIDS 2020: Virtual).

The only currently licensed PrEP medications--daily oral pills containing the HIV drugs tenofovir and emtricitabine--are highly effective at preventing HIV when taken as prescribed. However, taking a pill daily can be challenging. A long-acting form of PrEP could offer a less frequent, more discreet option that may be more desirable for some people. HPTN 083 and an ongoing companion study called HPTN 084, which is evaluating long-acting injectable cabotegravir for HIV prevention in cisgender women in sub-Saharan Africa, are sponsored by NIH's National Institute of Allergy and Infectious Diseases (NIAID).

In May 2020, a planned interim review of HPTN 083 data indicated a high level of efficacy for long-acting injectable cabotegravir among cisgender men and transgender women who have sex with men. The results reported today are based on a more extensive analysis of interim data from 4,566 study participants.

Overall, the rate of HIV acquisition in the participants was low. Among the 52 participants who acquired HIV, 13 were in the study group who received the cabotegravir-based PrEP regimen plus placebo daily oral tablets, and 39 were in the group who received daily oral Truvada plus placebo injections. This translated to an HIV incidence rate of 0.41% (95% confidence interval [CI] 0.22%-0.69%) in the cabotegravir group and 1.22% (95% CI 0.87%-1.67%) in the Truvada group--indicating 66% lower incidence in the cabotegravir group. Detailed analysis of these data indicated that the superior efficacy of cabotegravir was statistically significant.

Both products were safe and generally well-tolerated. Participants in the cabotegravir group were more likely to experience fever and pain or tenderness at the injection site compared to those in the Truvada group, who received placebo injections. Those in the Truvada group were more likely to report nausea. Most participants in the cabotegravir group received their injections as scheduled, with only 46 people (2.2%) discontinuing injections. Adherence to daily Truvada was also high, with 87% of a subset of 372 participants who provided blood samples having some detectable concentrations of the drug. Study investigators are continuing to follow the HPTN 083 study participants and to gather and analyze additional data on the long-term safety of injectable cabotegravir for HIV prevention.

NIAID collaborates on HPTN 083 with ViiV Healthcare, Gilead Sciences, Inc., and the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-fund the trial, which is conducted by the HPTN. ViiV Healthcare and Gilead Sciences, Inc., provide study medications. Three other NIH institutes also collaborate on HPTN 083: the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. More information about HPTN 083 is available on ClinicalTrials.gov under identifier NCT02720094.

Amid news that the United States has bought up virtually the entire global supply of remdesivir, a new Boston University School of Public Health (BUSPH) study outlines how the drug could save lives in countries with less hospital capacity, such as South Africa, where COVID-19 is beginning to overwhelm intensive care units (ICUs).

Recent research has suggested that remdesivir can reduce deaths from COVID-19 by as much as 30%, but has a more significant effect on how long patients need intensive care, from an average of 15 days down to an average of 11 days.

The peer-reviewed study, published in the journal Clinical Infectious Diseases, estimates that remdesivir's ability to shorten ICU stays could increase the number of patients treated in South Africa's ICUs by more than 50%. This increased capacity could save as many as 6,862 lives per month as the country's cases peak. Add to that the potential lives saved directly from remdesivir treatment, and the drug could prevent the deaths of as many as 13,647 South Africans by December.

"There are many countries with limited ICU capacity that could benefit from this double impact on mortality," says study lead author Dr. Brooke Nichols, assistant professor of global health at BUSPH.

"Why would you use a drug--that has limited availability--to save one life when that same drug could be used to save two lives?"

Nichols says she is worried by the news that the U.S. has bought up the remdesivir supply, especially if the government doesn't even make sure that priority goes to overwhelmed U.S. locations.

"Because more lives can be saved per person treated when using remdesivir in places where ICU resources are breached, using remdesivir when ICU resources are not breached would be a misallocation of scarce resources," she says.

Nichols and study co-authors in Boston and South Africa have been modeling South Africa's COVID epidemic to help the country's government make informed decisions, and previously predicted that the country's ICU capacity could be overwhelmed as early as this month. The hardest-hit province, the Western Cape, exceeded ICU capacity in June.

For the remdesivir study, the researchers used their South African National COVID-19 Epidemiology model to look at the estimated three to six months when severe cases will exceed the country's 3,450 available ICU beds. If every one of South Africa's ICU patients with COVID received remdesivir, reducing the average ICU stay, the researchers estimated that the number of patients treated in ICUs from June to December would increase from between 23,443 and 32,284 patients to between 36,383 and 47,820.

The mortality rate for COVID-19 in ICUs varies from country to country and hospital to hospital, so the number of lives saved from increased ICU capacity would also vary. The researchers modeled several different scenarios, finding increased ICU capacity in South Africa could save 685 lives per month if a patient who needed intensive care was just as likely to die in an ICU than outside of one. At the other extreme, the researchers estimated that the increased ICU capacity from remdesivir could save as many as 6,682 lives per month if almost all patients who required but didn't receive ICU care died, but those who did receive ICU care had a 50-50 change of surviving.

If direct treatment with remdesivir also saved the lives of an additional 30 percent of patients--the current estimate for the drug--then the researchers estimated that remdesivir's "double impact" could save as many as 13,647 lives in South Africa by December.

Philadelphia, July 7, 2020 - Researchers have previously identified brain structural signatures associated with individual neurological diseases using techniques such as magnetic resonance imaging (MRI). In a new study, a team of scientists based in Germany has compared data from multiple studies to find brain structural abnormalities shared between four different neuropsychiatric conditions. The researchers also found brain signatures that were unique to individual conditions.

The work, led by Bernhard T. Baune, MD, PhD, and Udo Dannlowski, MD, PhD, University of Münster, Germany, appears in Biological Psychiatry, published by Elsevier.

Co-first author Nils Opel, MD, (together with Janik Goltermann, MSc) said of the work, "the identification of shared and disorder-specific brain structural signatures might enhance the future development of biologically informed diagnostic applications in psychiatry."

The team analyzed data collected as part of the effort by an international research consortium called ENIGMA, for "Enhancing Neuro Imaging Genetics through Meta Analysis," which uses genetic and imaging studies to understand brain diseases. The 11 multi-center studies collected brain-imaging data from over 12,000 people.

"We found that 4 major psychiatric disorders - major depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder - show a surprisingly high level of similarity in their brain structural abnormalities," said Dr. Opel. The shared brain areas showing structural aberrations were mainly in cortical areas associated with cognitive processing, memory and self-awareness.

On the flipside, Dr. Opel added, "we were able to identify regional abnormalities with high specificity for certain disorders." Interestingly, these distinct structural differences sometimes appeared in the same area for two disorders, but in opposite directions from the norm.

In contrast, attention-deficit/hyperactivity disorder and autism spectrum disorder did not share brain structural signatures with any other disorders. That may be because those disorders are considered developmental diseases with a distinct etiology from the other psychiatric conditions, which have more in common.

The researchers do not yet understand the mechanisms behind the shared structural elements, but a growing body of evidence shows that these psychiatric disorders also share common genetic as well as environmental influences, which might underlie the current findings.

"Our understanding arising from brain imaging studies of the biology of neuropsychiatric disorders is changing," said John H. Krystal, MD, Editor of Biological Psychiatry. "Initially, we focused on the individual properties of particular patient groups. Then, some imaging studies suggested that neuropsychiatric disorders were dimensionally related. This new study affirms the dimensional relationship among some disorders, but suggests that some categorical distinctions may exist at the biological level."

The finding of regional abnormalities specific to individual conditions, Dr. Opel added, "could help shift the focus of future psychiatric and neuroscientific research on brain regions that appear to be central to disorder-specific biological processes and hence might facilitate the discovery of mechanisms underlying the development of specific psychiatric disorders."

New Rochelle, NY, July 7, 2020--Fathers' prepartum social media posts can predict their risk of postpartum depression. A predictive model based on machine learning is described in the peer-reviewed journal Cyberpsychology, Behavior, and Social Networking. Click here to read the article now.

Fathers' social media posts were evaluated for changes in behavior (engagement with the platform), emotions, linguistic style, and discussion topics following the birth of their child.

"These findings could assist in the development of support and intervention tools for fathers during the prepartum period," says Adrian Shatte, PhD, Federation University, Melbourne, Australia and coauthors.

"To date, most parenting interventions have been mother-focused. Research indicates that online interventions that include gaming features may increase engagement. This may be a unique modality to consider for creating more father-inclusive prevention and treatment programs," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.

WASHINGTON--Extreme ocean surface waves with a devastating impact on coastal communities and infrastructure in the Arctic may become larger due to climate change, according to a new study.

The new research projects the annual maximum wave height will get up to two to three times higher than it is now along coastlines in areas of the Arctic such as along the Beaufort Sea. The new study in AGU's Journal of Geophysical Research: Oceans suggests waves could get up to 2 meters (6.6 feet) higher than current wave heights by the end of the century.

In addition, extreme wave events that used to occur once every 20 years might increase to occur once every two to five years on average, according to the study. In other words, the frequency of such extreme coastal flooding might increase by a factor of 4 to 10 by the end of this century.

"It increases the risk of flooding and erosion. It increases drastically almost everywhere," said Mercè Casas-Prat, a research scientist with Environment and Climate Change Canada's (ECCC) Climate Research Division and the lead author of the new study. "This can have a direct impact to the communities that live close to the shoreline."

Climate change in the Arctic

Earth's northernmost regions are a global warming hotspot, with some areas experiencing up to three times the warming of the rest of the world, Casas-Prat said. But researchers lack information on how the impacts may play out.

Casas-Prat and her co-author Xiaolan Wang, also with the ECCC, wanted to examine how global warming might impact extreme ocean surface waves in the Arctic. Casas-Prat said some northern communities are already reporting accelerated erosion in some areas and increased building damage due to extreme waves. A worsening of these ocean conditions will have a direct impact on coastal communities, energy infrastructure, shipping, and even ecosystems and wildlife.

Much of the Arctic is frozen for most of the year, but the warming climate is contributing to increasing periods of open water, which can become an issue when extreme waves are factored into the equation.

In the new study, the scientists gathered five sets of multi-model simulations of oceanic and atmospheric conditions like surface winds, which generate waves, as well as sea ice for the RCP8.5 scenario, a future scenario commonly used in climate change projections that assumes low efforts to curb emissions. Then they ran simulations of wave conditions for two periods, from 1979 to 2005 (historical), then from 2081 to 2100 (future). Using the ensemble of multi-model simulations, they were able to assess the uncertainty in the changes in the extreme Arctic waves due to the uncertainty present in the five climate models used.

One of their main findings was a projected notable wave height increase between these two periods in almost every place in the Arctic.

Among the hardest-hit areas was in the Greenland Sea, which lies between Greenland and the Norwegian archipelago of Svalbard. The study found maximum annual wave heights there could increase by as much as 6 meters (19.7 feet).

Casas-Prat said the models present a degree of uncertainty about how much waves heights might change, but she is confident there is going to be an increase. The researchers' predictions also showed that by the end of the century, the timing of the highest waves may also change.

"At the end of the century, the maximum will on average come later in the year and also be more extreme," Casas-Prat said.

Impact on communities

Judah Cohen, a climatologist at the Massachusetts Institute of Technology who was not involved in Casas-Prat's research, said these waves could be particularly devastating to coastal areas that have never previously experienced open water.

"The main conclusions of the paper are that waves will increase in height in the Arctic region and that Arctic coastlines are at greater risk to erosion and flooding are fairly straightforward," he said. "We are already seeing these increased risks along Arctic coastlines with damage to coastline structures that previously were never damaged."

The researchers examined one area of coastline along the Beaufort Sea in northern Alaska and Canada, which holds a number of communities as well as energy infrastructure, and also found notable wave height increases there.

Since larger waves can lead to increased risks of flooding and damage to coastal infrastructure, communities and development in this area might be affected by these waves. Flooding can also impact the availability of fresh water in some areas, as storm and wave surges can get into freshwater lagoons that communities rely on.

"As more and more ice melts and more of the Arctic ocean surface becomes exposed to the wind, waves will increase in height because wave height is dependent on the distance the wind blows over open waters," Cohen said.

In another recent study published in AGU's journal Geophysical Research Letters, Casas-Prat and Wang examined the contribution of sea ice retreat on the projected increases in extreme wave heights in the Arctic. They found that surface winds alone cannot explain the changes in the regional maximum wave heights.

"Sea ice retreat plays an important role, not just by increasing the distance over which wind can blow and generate waves but also by increasing the chance of strong winds to occur over widening ice-free waters," Casas-Prat said.

Increased waves could also increase the speed of ice breakup. The loss of ice due to waves could affect animals like polar bears which hunt seals on polar ice as well as a number of other creatures that rely on ice. It could also affect shipping routes in the future.

"Waves definitely have to be taken into account as an important factor to ensure those routes are safe," Casas-Prat said.

An analysis of data from more than 1,300 women followed prospectively through pregnancy found that women with lower levels of the essential mineral manganese in early pregnancy were more likely to develop the serious high blood pressure syndrome called preeclampsia in late pregnancy, according to a new study led by researchers from Johns Hopkins Bloomberg School of Public Health.

The study, published online in the journal Epidemiology, suggests the possibility that boosting manganese levels in women before and during pregnancy could potentially reduce preeclampsia risk.

Preeclampsia usually occurs after the 20th week of pregnancy and affects more than 100,000 women in the U.S. each year and an estimated 2 to 8 percent of pregnancies worldwide--and is trending towards higher rates. It features high blood pressure and associated organ damage, for example to the kidneys, and if untreated preeclampsia can lead to fatal complications such as stroke for mothers and/or premature birth for offspring. Risk factors include obesity, diabetes, and a family history of preeclampsia, but its root biological causes are unknown.

The new paper is thought to be the first to link preeclampsia to lower manganese levels in early pregnancy, long before preeclampsia appears. Prior epidemiological studies have found that women with preeclampsia tend to have lower manganese levels compared to women who don't have preeclampsia. This earlier research did not establish whether the variation in manganese levels preceded the development of preeclampsia.

"If our findings are confirmed by other prospective pre-birth cohorts, then this association between low manganese and preeclampsia should be examined experimentally, first in mice and then in humans," says study senior author Noel Mueller, PhD, assistant professor in the Department of Epidemiology at the Bloomberg School.

"These new findings are especially relevant, considering that preeclampsia rates are increasing and we still lack any good strategy for preventing it," says study first author Tiange Liu, MHS, a research data analyst at the Bloomberg School.

Mueller, Liu, and colleagues previously found, in a study published in 2019, that in a sample of more than 1,000 women from the Boston Birth Cohort, levels of manganese in red blood cells, as measured shortly after delivery, tended to be lower in women who had had preeclampsia.

For their new analysis, the researchers looked at data from another Massachusetts-based study called Project Viva, which was conducted in 1999-2002. The Project Viva dataset included preeclampsia outcomes and also levels of manganese in blood drawn in the first trimester of pregnancy. If preeclampsia in these cases tended to be preceded by low manganese levels months earlier, that would be an even stronger hint that low manganese levels can be a causative factor for this condition.

The sample included 1,312 women, of whom 48 (3.7 percent) developed preeclampsia.

The researchers in their analysis found that higher manganese levels in the first trimester were associated with a lower risk of preeclampsia later in the pregnancy, depending on the dose. This suggests that incrementally more manganese would bring incrementally less risk. The researchers divided the women into three equally sized groups according to their measured manganese levels--low, medium, and high--and found that those in the high-manganese group had just half the risk of preeclampsia, compared to those in the low-manganese group.

The study was observational and did not establish a causal relationship between higher manganese levels and lower preeclampsia risk. The findings suggest that further studies that could establish a causal relationship, including of high-manganese diets, might soon be advisable.

Many common foods such as mussels, brown rice, sweet potatoes, pine nuts, and spinach are relatively rich in manganese.

Manganese has multiple biological roles in human cells--in enzyme complexes, for example, that help protect cells from harmful oxygen-containing molecules. But how it would ward off preeclampsia is so far unclear. Studying cellular mechanisms during pregnancy would help illuminate how differences in manganese levels could account for changes in preeclampsia risk, the researchers say.

Boston, Mass. - Early in the COVID-19 pandemic, widespread cancellations of electively-scheduled or "non-emergency" operations were implemented to free up hospital beds and conserve protective equipment for health care workers. For some conditions, including cancer, timely surgery is critical for patients' survival. In a new study published in the Journal of Gastrointestinal Surgery, a team of investigators at Beth Israel Deaconess Medical Center (BIDMC) examined the effects of delaying surgery for gastrointestinal cancers.

The analysis examined the results of peer-reviewed studies published between 2005 and 2020 that investigated how surgical delays affect patients with colorectal, pancreatic or gastric cancer. "When we started this research, little knowledge existed about how long we could safely delay surgery for these cancers or how to prioritize which operations should occur first," said first author Scott C. Fligor, MD, a General Surgery resident at BIDMC. "In the context of the coronavirus pandemic, we were concerned that both surgeons and patients were forced to make decisions without a clear understanding of the risks of surgical delay."

Fligor and his colleagues identified 43 relevant studies related to colorectal cancer. A surgical delay of 30 to 40 days was associated with shorter survival times in patients with colon cancer, as was a delay of seven to eight weeks after chemotherapy and/or radiation therapy in patients with rectal cancer. For pancreatic cancer, nine studies were identified, and two studies found that cancer progression increased in patients who experienced surgical delays over 30 days. Six studies were included for gastric cancer, and none of the studies found worse patient survival with increased time to surgery.

"Surgical delay is associated with increased risk in some gastrointestinal malignancies," said Fligor. "While every effort should be made to avoid surgical delay, the COVID-19 pandemic may make such delays unavoidable."

Fligor stressed that delaying surgery does not necessarily mean delaying treatment. "Providers should consider whether alternative therapies can help to minimize the risk of delay, such as extending a course of chemotherapy before surgery or initiating chemotherapy when surgery would normally occur first," he said. "It is critical for patients to work with their health care team to create a safe plan for treatment during the pandemic. The right decision for each patient depends on several factors, including the type of cancer, treatments available, and the local burden of COVID-19."