Body

Scientists have shown that adding an experimental cancer drug to a widely used diabetes treatment improves blood glucose control and weight loss in mice, according to a study published today in eLife.

The results pave the way for clinical studies of the new drug combination as a more effective long-term treatment for millions of people with diabetes and obesity.

Glucagon-like peptide 1 agonists (GLP-1 analogs) are a relatively new class of drugs that reduce blood sugar levels and lower body weight. They partially function by binding to the glucagon-like peptide 1 receptor on pancreatic beta cells, which leads the cells to produce insulin. But not all patients achieve normalisation of blood glucose control with GLP-1 drugs, and very few achieve full reversal of obesity.

"We have previously shown that prolonged association of the GLP-1 agonists with the glucagon-like peptide 1 receptor supports insulin secretion in pancreatic beta cells," explains project team leader Dr. Prasenjit Mitra of the Dr. Reddy's Institute of Life Sciences. "This led us to see whether we could enhance the effects of GLP-1 agonism on regulating glucose levels with a complementary therapy."

The team started with a library of potential drugs and tested them in pancreatic beta cells to see if they enhanced the effects of a GLP-1 drug on incretin receptor activity, by measuring a second messenger molecule called cAMP. They found four molecules that enhanced GLP-1 drug activity. The most effective one, MS-275 (also called entinostat), generated 3.5 times the cAMP levels than the GLP-1 drug alone. MS-275 is a member of a drug family called class 1 HDAC inhibitors that are being investigated as treatments for other diseases including cancer.

Given the synergistic effect of the drugs in pancreatic beta cells, the team tested whether their findings would hold true in obese mice, fed a high-fat diet. Shilpak Bele, the graduate student under Dr. Mitra's direction, and other team members found that mice treated with the combination of GLP-1 agonist and MS-275 had a much lower fasting glucose level than control mice that were sustained with repeat dosing. Where a high-fat diet increased fasting blood sugar in the untreated mice, the mice on the combination treatment remained in control.

Given these effects on blood sugar, the team explored whether the combination treatment also minimised weight gain. Mice given the combination treatment had a significant and sustained reduction in their food intake, which resulted in weight loss. When treatment was interrupted, the mice regained weight. Once the treatment was resumed, only the mice receiving the combination treatment showed significant weight loss again.

"GLP-1 drugs have emerged in the last decade as unique medicines that provide substantial improvements in glycemic control and body weight; however, they seldom achieve full metabolic recovery or help treat associated comorbidities such as body weight," Dr. Mitra explains. "Our results suggest that the class 1 HDAC inhibitor MS-275 can significantly enhance the action of GLP-1 drugs, more effectively normalising blood glucose and reducing weight gain. This lays the foundation for clinical studies of combinations of GLP-1/HDAC inhibitors for the long-term management of diabetes and obesity in humans."

Surgery, in addition to treatments like chemotherapy and radiation therapy, may increase the length of survival for metastatic breast cancer patients, according to Penn State College of Medicine and Penn State Cancer Institute researchers. They studied nearly 13,000 stage four breast cancer patients and found that those who had surgery in addition to their other treatments had a survival advantage over those who had other treatments alone.

Stage four breast cancer accounts for 6% of newly diagnosed breast cancer cases. Systemic therapy, which may include treatments like chemotherapy, hormone therapies and immunotherapies, is routinely part of treatment plans for those patients. The benefits of surgery to remove the primary breast cancer are currently only recommended for relieving symptoms of advanced breast cancer such as pain and bleeding.

Surgery is the standard of care for some other types of cancers that have spread from the site of origin to another part of the body, known as metastatic cancers. Dr. Kelly Stahl, surgical resident and lead author of the study published in the Annals of Surgical Oncology, said that previous studies evaluating surgical interventions for metastatic breast cancer had conflicting results which has led to a lack of consensus among clinicians and researchers.

"Results from previous trials evaluating surgical benefit in metastatic breast cancer patients have been questioned because of the small number of participants or the fact that patients weren't also receiving chemotherapy or other systemic therapies," Stahl said. "We felt another key factor missing from those studies was whether the biologic subtype of breast cancer affected the survival rates in relation to surgical intervention."

Stahl worked with Dr. Daleela Dodge and Chan Shen to identify 12,838 stage four breast cancer patients from the National Cancer Database from 2010-2015 and whether these patients' cancer cells had a growth-promoting protein called HER2 and hormone receptors for estrogen and progesterone, which can fuel cancer growth. The researchers said knowing these characteristics of a cancer's biological subtype can help determine which treatment plans may be effective.

Stahl studied patients who either had systemic therapy alone, had systemic therapy and surgery, or had systemic therapy, surgery and radiation. She and her coauthors then evaluated whether certain biologic subtypes and timing of chemotherapy were associated with survival advantages.

"We evaluated whether the hormone status had an influence on surgical benefit in these treatment-responsive breast cancer patients," said Dodge, an associate professor of surgery and humanities. "Some types of breast cancer, especially like triple negative, where the cancer is hormone receptor and HER2 negative, are not very responsive to treatment. So our goal was to see if surgery made a difference in metastatic breast cancers that were responsive to treatment."

The researchers excluded patients who died within six months of their diagnoses, in order to ensure that treatment-responsive cancers were being studied. They found that patients with a surgical intervention tended to have a longer length of survival compared to patients with other treatment plans. Patients whose cancers were HER2 positive especially saw prolonged survival when their treatment plan included surgery.

Stahl and her coauthors further analyzed the patients who received surgery to see whether receiving chemotherapy before or after surgery had an impact on their length of survival. They found that regardless of hormone receptor or HER2 status, patients who received systemic therapy -- including chemotherapy and targeted treatments -- before surgery tended to live longer than those who had surgery before systemic treatment.

"Not only did we find that surgery may be beneficial for treatment-responsive metastatic breast cancer patients, we also uncovered that getting chemotherapy before that surgery had the greatest survival advantage in patients with positive HER2 and estrogen and progesterone receptor status," said Shen, associate professor of surgery.

The researchers said that randomized, controlled trials evaluating the role of surgery after systemic therapy in a younger demographic with minimally metastatic cancers could be used to confirm their results, but said that patient resistance to randomization in trials like this have resulted in poor study recruitment. Therefore, they encourage clinicians to evaluate real-world evidence, including their study, to choose optimal treatment for metastatic breast cancer patients.

"Stage four breast cancer patients who are responsive to systemic therapy may be able to benefit from the addition of surgery regardless of their biologic subtype," Stahl said.

HERSHEY, Pa. -- Surgery, in addition to treatments like chemotherapy and radiation therapy, may increase the length of survival for metastatic breast cancer patients, according to Penn State College of Medicine and Penn State Cancer Institute researchers. They studied nearly 13,000 stage four breast cancer patients and found that those who had surgery in addition to their other treatments had a survival advantage over those who had other treatments alone.

Stage four breast cancer accounts for 6% of newly diagnosed breast cancer cases. Systemic therapy, which may include treatments like chemotherapy, hormone therapies and immunotherapies, is routinely part of treatment plans for those patients. The benefits of surgery to remove the primary breast cancer are currently only recommended for relieving symptoms of advanced breast cancer such as pain and bleeding.

Surgery is the standard of care for some other types of cancers that have spread from the site of origin to another part of the body, known as metastatic cancers. Dr. Kelly Stahl, surgical resident and lead author of the study published in the Annals of Surgical Oncology, said that previous studies evaluating surgical interventions for metastatic breast cancer had conflicting results which has led to a lack of consensus among clinicians and researchers.

"Results from previous trials evaluating surgical benefit in metastatic breast cancer patients have been questioned because of the small number of participants or the fact that patients weren't also receiving chemotherapy or other systemic therapies," Stahl said. "We felt another key factor missing from those studies was whether the biologic subtype of breast cancer affected the survival rates in relation to surgical intervention."

Stahl worked with Dr. Daleela Dodge and Chan Shen to identify 12,838 stage four breast cancer patients from the National Cancer Database from 2010-2015 and whether these patients' cancer cells had a growth-promoting protein called HER2 and hormone receptors for estrogen and progesterone, which can fuel cancer growth. The researchers said knowing these characteristics of a cancer's biological subtype can help determine which treatment plans may be effective.

Stahl studied patients who either had systemic therapy alone, had systemic therapy and surgery, or had systemic therapy, surgery and radiation. She and her coauthors then evaluated whether certain biologic subtypes and timing of chemotherapy were associated with survival advantages.

"We evaluated whether the hormone status had an influence on surgical benefit in these treatment-responsive breast cancer patients," said Dodge, an associate professor of surgery and humanities. "Some types of breast cancer, especially like triple negative, where the cancer is hormone receptor and HER2 negative, are not very responsive to treatment. So our goal was to see if surgery made a difference in metastatic breast cancers that were responsive to treatment."

The researchers excluded patients who died within six months of their diagnoses, in order to ensure that treatment-responsive cancers were being studied. They found that patients with a surgical intervention tended to have a longer length of survival compared to patients with other treatment plans. Patients whose cancers were HER2 positive especially saw prolonged survival when their treatment plan included surgery.

Stahl and her coauthors further analyzed the patients who received surgery to see whether receiving chemotherapy before or after surgery had an impact on their length of survival. They found that regardless of hormone receptor or HER2 status, patients who received systemic therapy -- including chemotherapy and targeted treatments -- before surgery tended to live longer than those who had surgery before systemic treatment.

"Not only did we find that surgery may be beneficial for treatment-responsive metastatic breast cancer patients, we also uncovered that getting chemotherapy before that surgery had the greatest survival advantage in patients with positive HER2 and estrogen and progesterone receptor status," said Shen, associate professor of surgery.

The researchers said that randomized, controlled trials evaluating the role of surgery after systemic therapy in a younger demographic with minimally metastatic cancers could be used to confirm their results, but said that patient resistance to randomization in trials like this have resulted in poor study recruitment. Therefore, they encourage clinicians to evaluate real-world evidence, including their study, to choose optimal treatment for metastatic breast cancer patients.

"Stage four breast cancer patients who are responsive to systemic therapy may be able to benefit from the addition of surgery regardless of their biologic subtype," Stahl said.

An important new finding by University of Cincinnati researchers could help slow the transmission of HIV/AIDS and reduce pregnancies among adolescent girls in rural South Africa.

"Use a condom" has long been accepted globally as the primary message to prevent pregnancy and the spread of HIV/AIDS, but when it comes to the acceptability of adding an extra method (i.e. birth control pills, injectables and IUDs) to prevent pregnancy, female adolescents in rural South Africa remain unaware of these methods and instead place more emphasis on nonmedical interventions, according to research by the University of Cincinnati.

"Our findings are that these young women placed less emphasis on paring a condom with the additional use of highly effective, modern contraceptive methods," as a dual means of protection for both pregnancy and HIV/AIDS, and more emphasis on peer, parental and environmental factors, says lead author Jennifer Brown, a UC associate professor of psychology and psychiatry.

Currently, South Africa has the highest number of individuals living with HIV in the world, with greater health disparities experienced by Black South Africans. National data points to high rates of sexual activity among South African adolescents, with only an approximate one-third using modern contraceptive methods, heightening the risk for unplanned adolescent pregnancies.

The study, which currently appears in the Journal of Adolescent Health, was funded by a $100,000 grant from Grand Challenges Explorations, an initiative of the Bill & Melinda Gates Foundation, in collaboration with UC, Emory University, the University of Houston and South Africa's University of the Free State.

The research, comprising 450 participants, bore out a prevailing theme: While young people were aware of condoms, they had a limited awareness of the full range of dual prevention methods and relied more on other influences. For example, adolescents emphasized the importance of focusing on one's future, affiliating with a positive peer group and following the advice of parents or elders as influential to sexual decision-making.

While it's not surprising that adding another measure to condom use might be elusive to youth in any rural environment, Brown says it should be the converse here; because South Africa has experienced disproportionate prevalence of HIV/AIDS and has placed a greater emphasis on educating teenagers regarding prevention.

"Youth here are more educationally advanced and open about sexual health than Western nations, but the problem is that education has been singularly focused on HIV/AIDs and less on pregnancy."

In the midst of the raging coronavirus pandemic, we're faced with agonizing decisions about whether to forgo treasured holiday rituals. Many people have defied health officials, putting themselves at risk of contracting COVID-19 or spreading the disease in order to uphold their family traditions in person.

A new paper by two researchers at UC Berkeley's Haas School of Business sheds light on the psychology of rituals--and why health officials may have to do more than just tell people not to gather in order to be effective.

That's because coming together to exchange gifts on Christmas isn't just about getting presents; it's a symbol of love. Eating turkey on Thanksgiving isn't just a shared meal; it's an expression of gratitude. "We view rituals as more important than regular types of group activities because they reflect the values of the group," says Dan Stein, a Berkeley Haas doctoral student and lead author on the paper.

"When people alter activities that are more ritualistic, it elicits stronger moral outrage," says Juliana Schroeder, an assistant professor in the Haas Management of Organizations Group and the paper's co-author. Pitting pandemic social distancing against the values of love and togetherness represented by the holidays creates moral conflict for many people. "If messages from officials to social distance are going to be successful, they must come up with a response to these strong group values."

The paper, forthcoming in the Journal of Personality and Social Psychology, examines the psychology of rituals through experiments that drive home just how strongly people feel about traditions and resist even minor changes. It was co-written by Harvard Business School professors Francesca Gino and Michael Norton along with Nicholas Hobson, founder of The Behaviorist consulting firm.

In one experiment, the researchers asked Berkeley undergraduate students to rate 15 holidays according to how ritualistic they were. They then asked them to rate on a scale of 1 to 7 how angry and frustrated they would feel if the U.S. government "moved celebrations for the holiday one week forward," and also how immoral and inappropriate it would be to change the date. The more ritualistic the holiday, the higher it scored on both scales, signifying stronger "moral outrage" about altering it. Christmas and New Year's scored above 5 on both scales, while Columbus Day scored as a 2 on both.

In other experiments, they found that altering a ritual elicits moral outrage even if a person has a good reason for doing so. When they asked participants--all U.S. citizens--how they would feel if they saw another citizen remaining seated rather than standing for the Pledge of Allegiance, participants reported outrage even when they were told the person was sitting to show solidarity with Americans with disabilities. Participants expressed even more outrage, however, when told that the person was sitting to protest U.S. values--indicating that the reason for the change was important--and they were also upset if told that the person had forgotten to stand. Their irritation only subsided when they were told the person was injured and physically unable to stand.

Even changes that might make a ritual safer elicit moral outrage, they found. In another experiment, the researchers asked Jewish participants how they would feel if a circumcision ceremony--a highly ritualized event occurring the same way for thousands of years--was done in a hospital rather than at a temple. Over 80% of respondents agreed that a hospital ceremony would be safer, and yet they also reported more anger about the suggestion of moving the circumcision ceremony to a hospital rather than keeping it the same, even if it was riskier.

"People don't want to have to pit one sacred value against another," Stein says. "While medical safety represents the sacred value of life in Judaism, circumcision stands for a literal blood covenant with God. That creates an uncomfortable conflict in people's minds."

In fact, the researchers found that the study participants who were most committed to U.S. values expressed the most outrage about changing holiday traditions. "We theorize that moral outrage is functional in the long-run because it can help a group protect its sacred rituals," Stein says. "We need those people who are committed for the group to survive, but our research suggests that trying to tell people, 'By not practicing your ritual, you'll save lives,' might not be effective for everyone."

The challenge for families trying to stay safe during the pandemic is how to alter rituals in ways that keep their values intact, even if getting together physically isn't possible. "This research suggests that to reduce outrage when altering rituals, you should try to change them in ways that still allow people to celebrate group values," says Schroeder. "That's what people are getting upset about when the ritual is altered--and that's the thing that needs to be maintained."

A new report from researchers at the Johns Hopkins Bloomberg School of Public Health offers recommendations aimed at federal, state, and local policymakers to address the opioid epidemic during the pandemic, which has seen sharp increases in fatal and nonfatal overdoses. The recommendations detail policy solutions in the areas of data and surveillance, harm reduction, and treatment, with special considerations for vulnerable populations.

The report, Saving Lives from Overdose During a Pandemic, draws from peer-reviewed research on opioid overdoses, as well as recommendations from the World Health Organization and the Centers for Disease Control and Prevention.

A majority of states--more than 40--have reported increases in opioid-related deaths since the beginning of the pandemic, according to the ODMAP report, a mapping program that collects suspected fatal and non-fatal overdoses in real time across jurisdictions in the United States. Nationwide, there's been an 18 percent increase in overdoses since the beginning of 2020, according to ODMAP.

Among the new report's recommendations, the researchers provide guidance around increasing the capacity for state and local health departments to track and report changes in drug-related data during the pandemic. Specifically, they recommend using federal funding to support creating new data management systems that automatically assemble data to allow for more timely analysis. They also recommend that research focus on racial disparities and health inequities to inform equitable solutions to both the COVID-19 pandemic and the opioid epidemic.

The authors call for state and local jurisdictions to declare syringe service programs--community-based organizations that provide support services, linkages to substance use treatment, and access to safer drug use supplies--to be essential services during the pandemic. Many of these programs have been disrupted due to pandemic mitigation efforts, leaving clients with fewer resources. In addition, the report recommends that state and local jurisdictions issue emergency orders that make it easier to distribute harm reduction materials such as clean syringes and naloxone, a medication that reverses overdoses, to community-based organizations and service providers.

"The pandemic compounded an existing crisis--the opioid epidemic--with high unemployment rates, social isolation, and despair, all known risk factors for substance use," says Sara Whaley, MPH, MSW, research associate in the Bloomberg School's Department of Health Policy and Management and lead author of the report. "We have to support treatment providers, health departments, and other services that support people with substance use disorder, so they can provide essential, lifesaving services to those most in need."

The COVID-19 pandemic has resulted in nearly 18 million total cases in the U.S., and nearly 318,000 deaths, since January 2020. According to the Centers for Disease Control and Prevention, opioid-related overdoses accounted for over 47,000 deaths in 2018, the last year for which data are available. Drug-related deaths are four times greater than they were in the 1990s.

The report, issued by faculty at the Bloomberg School and several research collaborators, also drew from the Overdose Detection Mapping Application Program, open-source, and statewide data dashboards.

The report also recommends expanding access to substance use treatment, including medications like methadone and buprenorphine which are prescribed to reduce the negative effects of substance use. The researchers call upon Congress to appropriate additional funding to the Substance Abuse and Mental Health Services Administration to expand buprenorphine distribution via telehealth and delivery of methadone to patients at home. While federal rules now have more flexibility in these treatment options than prior to the pandemic, state restrictions may still be in place. The report calls for states to eliminate requirements that limit access to or billing for telemedicine. Finally, the researchers recommend increasing mobile treatment services to reach those living in poverty or experiencing homelessness as well as ensuring treatment providers have access to adequate personal protective equipment to protect themselves and the patients.

The researchers also suggest that states should utilize existing community health infrastructure of treatment and outreach programs to aid in the distribution of vaccines to critical populations of people who use drugs. They also recommend the release of people in jails and prisons who were arrested for low-level offenses, increased support of individuals released from jail or prison, and immediate provision of Medicaid coverage to individuals upon release. Additionally, they encourage states to prioritize emergency funding to establish COVID-19 shelters that accept individuals with substance use disorders.

"There are pathways to addressing the overdose crisis and the COVID-19 crisis together," says Joshua Sharfstein, MD, vice dean for Public Health Practice and Community Engagement, professor of Practice in Health Policy and Management, and director of the Bloomberg American Health Initiative. "This report provides a roadmap for saving lives."

We live in a world invaded by plastic. Its role as a chemically stable, versatile and multi-purpose fostered its massive use, which has finally translated into our current situation of planetary pollution. Moreover, when plastic degrades it breaks into smaller micro and nanoparticles, becoming present in the water we drink, the air we breathe and almost everything we touch. That is how nanoplastics penetrate the organism and produce side effects.

A revised study led by the Universitat Autónoma de Barcelona (UAB), the CREAF and the Centre for Environmental and Marine Studies (CESAM) at the University of Aviero, Portugal, and published in the journal Science Bulletin, verifies that the nanoplastics affect the composition and diversity of our intestinal microbiome and that this can cause damage to our health. This effect can be seen in both vertebrates and invertebrates, and has been proved in situations in which the exposure is widespread and prolonged. Additionally, with alteration of the gut microbiome come alterations in the immune, endocrine and nervous system and therefore, although not enough is known about the specific physiological mechanisms, the study alerts that stress to the gut microbiome could alter the health of humans.

The health effects of being exposed to nanoplastics was traditionally evaluated in aquatic animals such as molluscs, crustaceans and fish. Recent in vitro analyses, using cell cultures of fish and mammals, has allowed scientists to analyse the changes in gene expression associated with the presence of nanoplastics from a toxicological viewpoint. The majority of neurological, endocrine and immunological tracts in these vertebrates are very similar to those of humans, and therefore authors warn that some of the effects observed in these models could also be applied to humans. Understanding and analysing the process through which these plastic fragments penetrate the organism and harm it is fundamental, as is determining precisely the amount and typology of nanoplastics polluting the environment. For this reason, researchers highlight not only the need to further study the specific mechanisms and effects on human cell models, but also unify analysis methodologies in order to conduct correct measurements of the quantity of nanoplastics present in different ecosystems.

Mariana Teles, researcher at the UAB, in collaboration with other researchers such as Josep Peñuelas, CSIC lecturer at the CREAF, comments that "this article does not aim to raise the alarm, but it does seek to warn about the fact that plastic can be found in almost everything surrounding us, it does not disintegrate and we are constantly exposed to it. At the moment, we can only speculate on the long-term effects this can have on human health, although we already have evidence in several studies describing hormonal and immune alterations in fish exposed to nanoplastics, and which could be applied to humans".

Invasive and Toxic

The study presents the main environmental sources through which nanoplastics enter the human body and summarises how they are able to penetrate the body: by ingesting them, occasionally inhaling them, and very rarely by being in contact with human skin.

Once they are ingested, up to 90% of the plastic fragments that reach the intestine are excreted. However, one part is fragmented into nanoplastics which are capable, due to their small size and molecular properties, to penetrate the cells and cause harmful effects. The study establishes that alterations in food absorption have been described, as well as inflammatory reactions in the intestinal walls, changes in the composition and functioning of the gut microbiome, effects on the body's metabolism and ability to produce, and lastly, alterations in immune responses. The article alerts about the possibility of a long-term exposure to plastic, accumulated throughout generations, could give way to unpredictable changes even in the very genome, as has been observed in some animal models.

The team in which Mariana Teles (Evolutive Immunology Group, IBB-UAB) is member also recently published a second article analysing the effects of nanoplastics in fish. The study, which is the result of Irene Brandts' PhD thesis directed by Nerea Roher, was published in Environmental Science: Nano and analyses the consequences of being exposed to nanoplastics to the immune system of a zebrafish (a small tropical fish widely used as a model organism for research). The scientists conclude that the nanoplastics can accumulate both in the cells and in the embryos of the zebrafish, additionally causing changes in the levels of genes relevant to the correct functioning of the animal's immune system. Despite this fact, the capacity of zebrafish embryos to survive a bacterial infection was not affected by the exposure to nanoplastics. The team of researchers nonetheless defend the need to continue research in this field, given that the presence of microplastics and nanoplastics in our ecosystems is an extremely crucial environmental issue which needs answers in order to understand how far-reaching any possible consequences may be.

Responsible usage

The review study acknowledges that different techniques are being tested to eliminate nanoplastics from the water, such as filtration, centrifugation and flocculation of wastewater, and the treatment of rainwater. Although the results are promising, they are limited to treating larger particles of plastics, and therefore until date no effective solution has been found for the elimination of nanoplastics from the environment.

"To solve this problem of plastic pollution, human routines must change and policies should be based on informed decisions on the known risks and available alternatives. Individual actions such as the use of more environmentally-friendly products and an increase in recycling indexes are important", Mariana Teles comments.

"The authorities can promote these pro-environmental actions through economic stimuli, such as tax benefits for reusing plastic as industrial raw material, as well as bottle deposit schemes for consumers", researchers recommend.

Potato is the most consumed vegetable crop worldwide. However, despite its importance, potato production is severely affected by high susceptibility to a wide range of microbial pathogens, such as bacteria from the genus Pectobacterium, which cause various devastating diseases in potato and produce important economic losses.

Even though resistance to Pectobacterium species is limited within cultivated potato varieties, it is known that a potato wild relative (S. chacoense) is resistant to them; however, until recently, the underlying mechanisms of this phenomenon remained unknown.

In a recent study published in the Molecular Plant-Microbe Interactions (MPMI) journal, scientists from Colorado State University (CSU) revealed that metabolites from S. chacoense contribute to disease resistance by altering the pathogenic behavior of Pectobacterium brasiliense, rather than inhibiting its growth or killing it.

"We tested if chemicals extracted from the wild potato affect the behavior of the bacterium and found that these inhibited their ability to produce the enzymes that degrade plant cell walls. The chemicals also intercepted their ability to communicate with each other. To use a battle analogy, the wild potato plant chemicals intercepted the bacteria's missiles, they cut off their radio communications, and together this encouraged the bacteria to remain friendly neighbors," explained Adam Heuberger, a CSU Associate Professor involved in the research.

"This wild potato is also resistant to insects, viruses, and fungi. The question is always why, and then how, we can translate this information to improve society. There is much to learn by studying wild relatives of food and ornamental plants," Heuberger added.

WASHINGTON - (December 18, 2020) A new study looking at the results of testing children for COVID-19 through a Children's National Hospital community-based testing site found that one in four patients had a positive test. The findings, reported online Dec. 18 in The Journal of Pediatrics, reinforce that children and young adults are impacted by the virus more than originally believed, and that the continued understanding of their role in transmitting COVID-19 is essential to getting the virus under control.

Of the 1,445 patients tested at the specimen collection site for SARS-CoV-2 virus between March 21 and May 16, 2020, the median age was 8 years old, and more than 34% of positive patients were Hispanic, followed by non-Hispanic Black and non-Hispanic white. The daily positivity rate increased over the study period, from 5.4% during the first week to a peak of 47.4% in May. Children and adolescents were referred to the testing site because of risk of exposure or mild symptoms.

"We knew that community-based testing sites were key in minimizing exposure risk to other patients and health care workers, preserving PPE, centralizing specimen collection services, mitigating acute care site overcrowding and informing our community of the burden caused by this disease," says Joelle Simpson, M.D., medical director of Emergency Preparedness at Children's National.

Drive-through/walk-up testing sites outside of a traditional acute care setting have emerged around the world to meet the need for testing mildly ill or asymptomatic individuals. In March, Children's National Hospital opened a drive-up/walk-up location - one of the first exclusively pediatric testing sites for the virus in the U.S. -- where primary care doctors in the Washington, D.C., region could refer young patients for COVID-19 specimen collection and testing.

"At first, children were not the target of testing initiatives, but it is clear that making testing available to pediatric patients early was a very important part of the pandemic response," says Meghan Delaney, D.O., M.P.H., chief of Pathology and Laboratory Medicine at Children's National. "Not only can children get severe disease, they can be part of positive clusters with the adults they live with. The knowledge we have gained by testing many thousands of children over the pandemic has provided key information."

Compared with non-Hispanic white children and after adjustments for age, sex and distance of residence from specimen collection site, minority children had a higher likelihood of infection.

"We wanted to identify the features of children tested at this site who did not require acute medical care and be able to compare demographic and clinical differences between patients who tested positive and negative for COVID-19," says Dr. Simpson.

Patients with COVID-19 exposure and symptoms were more likely to have a positive test than patients without symptoms. This supports contact tracing for symptomatic cases and testing as an important tool in detecting and containing community spread, according to the study's findings. Although most patients were referred because they lived with a family member with high risk for exposure or infection, this was not associated with positive test results.

"The impact of this virus is broad and affects planning for children, especially as schools and childcare centers work to reopen," Dr. Simpson says. "In order to guide the development of measures to control the ongoing pandemic, we need better understand the transmission potential of these mildly symptomatic or well children and young adults."

Boston -- As colleges and universities consider strategies for the spring semester to keep COVID-19 cases down, a study conducted by experts in epidemic modeling may help shed light on what mitigation strategies may be most effective, both in terms of infections prevented and cost. Investigators from Brigham and Women's Hospital, Massachusetts General Hospital and Case Western Reserve University used the Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model to perform their study, finding that combining a mandatory mask-wearing policy with extensive social distancing would prevent 87 percent of infections among students and faculty. Routine testing was also highly effective at preventing infections, but may be cost prohibitive for many colleges and universities. The team also reports that, even if campuses remain closed, there would likely be infections among faculty acquired from the surrounding community, as well as infections among students who return to live off campus in and around college towns. Results are published in Annals of Internal Medicine.

"This next semester represents a critical time in the pandemic. While the vaccine rollout has begun, it is unlikely that most college students will be eligible for the vaccine until late in the spring semester," said lead author Elena Losina, PhD, Director of the Policy and Innovation eValuations in Orthopedic Treatments (PIVOT) Center at the Brigham. "However, our modeling shows that colleges and universities can put effective programs in place to mitigate infections. This analysis is designed to help individuals and institutions make decisions using a formal, data-driven approach."

The team evaluated 24 mitigation strategies based on four approaches: social distancing, mask-wearing policies, isolation, and laboratory testing. The team compared results from a minimal social distancing program, in which only large gatherings such as sporting events or concerts were cancelled, and an extensive social distancing program, where all large classes and 50 percent of smaller classes were delivered online. Laboratory testing ranged from no testing of asymptomatic students and faculty to routine testing at 14-, 7-, or 3-day intervals.

The team's modeling predicted that:

No mitigation: Without any mitigation efforts, approximately 75 percent of students and 16 percent of faculty would become infected on a college campus.

Campus closed: Closing the campus would reduce student infections by 63 percent with most infections coming from those students living off campus.

Minimum social distancing: Student infections would be reduced by only 16 percent.

Mandatory masking: Universal masking would be more effective in preventing infections than either minimum or extensive social distancing.

Combining social distancing and masking: A mask-wearing policy with extensive social distancing would prevent 87 percent of infections among students and faculty and would cost $170/infection prevented.

Routine testing: Adding routine laboratory testing to a policy involving extensive social distancing and mask-wearing reduced infections the most, but at a high cost/infection prevented.

"If colleges put less effort into social distancing and mask-wearing policies, they need to rely more on routine laboratory testing at higher cost to reduce the spread of COVID-19. If less costly tests were available, then routine testing would be feasible in more college settings," said co-senior author Kenneth A. Freedberg, director of the Medical Practice Evaluation Center at Massachusetts General Hospital and a professor of Medicine at Harvard Medical School.

"This analysis quantifies the value of implementing and committing to mask-wearing and social distancing in college campuses as a key to operating safely during the COVID-19 pandemic," said co-senior author Pooyan Kazemian, PhD, an assistant professor of operations in the Weatherhead School of Management at Case Western Reserve University. "Extensive social distancing in college campuses with a hybrid educational system, combined with a mandatory mask-wearing policy, can prevent the vast majority of COVID-19 cases on college campuses."

While the researchers tried to capture the major COVID-19 mitigation strategies colleges are considering, the study could not examine all strategies and the analysis was restricted to one semester.

"It's critical to consider the tradeoffs and costs of mitigation efforts and what's feasible for colleges and universities whose budgets vary widely," said Losina. "Our analysis showed how colleges can develop strategies to help keep infections at bay. We hope that by the end of next semester, vaccines will be available to many students and faculty. Until then, preventing infections should continue to be the highest priority."

PHILADELPHIA, Dec. 21 - As COVID-19 vaccines are becoming available, physicians and other health care professionals must do the hard work of making sure sufficient numbers of people are vaccinated to end the pandemic. To help prepare them, the American College of Physicians (ACP) and Annals of Internal Medicine hosted the COVID-19 Vaccine Forum II - Promoting COVID-19 Vaccination on Dec. 16 where a panel of infectious disease experts discussed strategies for gaining public trust and acceptance of the vaccine. This was the second in a series of vaccine forums hosted by ACP and Annals of Internal Medicine.

ACP and Annals of Internal Medicine invited four experts to offer their perspectives on the vaccine and the current barriers to optimal uptake. Panelists included Dr. Ada Adimora from University of North Carolina, Dr. Helene Gayle from the Chicago Community Trust, Dr. Peter Hotez from Baylor University, and Dr. Heidi Larson from the London School of Tropical Medicine. Dr. Ryan Mire, a member of ACP's Board of Regents and a practicing internist in Nashville and Dr. William Schaffner from Vanderbilt University moderated the discussion. The full recording is available for replay here and is published in Annals of Internal Medicine along with commentary by Christine Laine, MD, MPH, ACP senior vice president and editor-in-chief, Annals of Internal Medicine; Deborah Cotton, MD, MPH, deputy editor, Annals of Internal Medicine, and Darilyn V. Moyer, MD, Executive Vice President and CEO, ACP.

"The vaccine does no good if it remains in freezers and vials-- we need to get the vaccine into people," said Dr. Laine. "Our members are in a unique position to assuage patients' fears and encourage vaccine acceptance. We developed these forums to arm physicians with the facts and strategies they will need to address vaccine apprehension in their clinical practice."

During the forum, the panelists discussed the current vaccines, when and how they might be disseminated to patients, bearing fairness and equity in mind, and the challenges ahead related to influencing public opinion about the safety of the vaccine. Panelists stressed the need to build trust among disproportionally affected minority communities to ensure adequate uptake of the COVID-19 vaccines. Every member of the panel agreed that a comprehensive public health communications campaign would be needed to promote the vaccine and refute the glut of misinformation that has been circulating online.

"We must help our patients understand that getting the COVID-19 vaccine is not just about protecting their health, but it is also about protecting the health of those around them," said Jacqueline W. Fincher, MD, MACP, president, ACP. "Being well-prepared for conversations about vaccine hesitancy is the first step in helping to make our communities safer for everyone."

Robust evidence from a large international study confirms that a difference in blood pressure readings between arms is linked to greater risk of heart attack, stroke and death.

Led by the University of Exeter, the global INTERPRESS-IPD Collaboration conducted a meta-analysis of all the available research, then merged data from 24 global studies to create a database of nearly 54,000 people. The data spanned adults from Europe, the US, Africa and Asia for whom blood pressure readings for both arms were available.

Funded by the National Institute for Health Research (NIHR) and published today in Hypertension, the study is the first to conclude that the greater the inter-arm blood pressure difference, the greater the patient's additional health risk.

Currently, international blood pressure guidelines advise health professionals to measure blood pressure in both arms when assessing cardiovascular risk,- yet this is widely ignored. The new study provides a new upper limit of 'normal' for an inter-arm difference in blood pressure, which is significantly lower than the current guidance. The research could lead to a change in international hypertension guidelines, meaning more at-risk patients could be identified and receive potentially life-saving treatment.

In a methodology that put patients at its heart, working with a patient advisory group at every step of the research, the team analysed data on inter-arm blood pressure difference, and tracked the number of deaths, heart attacks and strokes that occurred in the cohort over 10 years.

Lead author and GP Dr Chris Clark, of the University of Exeter Medical School, said: "Checking one arm then the other with a routinely used blood pressure monitor is cheap and can be carried out in any healthcare setting, without the need for additional or expensive equipment. Whilst international guidelines currently recommend that this is done, it only happens around half of the time at best, usually due to time constraints. Our research shows that the little extra time it takes to measure both arms could ultimately save lives".

"We've long known that a difference in blood pressure between the two arms is linked to poorer health outcomes. The large numbers involved in the INTERPRESS-IPD study help us to understand this in more detail. It tells us that the higher the difference in blood pressure between arms, the greater the cardiovascular risk, so it really is critical to measure both arms to establish which patients may be at significantly increased risk. Patients who require a blood pressure check should now expect that it's checked in both arms, at least once."

Blood pressure rises and falls in a cycle with each pulse. It is measured in units of millimetres of mercury (mmHg), and the reading is always given as two numbers: the upper (systolic) reading represents the maximum blood pressure and the lower (diastolic) value is the minimum blood pressure. A high systolic blood pressure indicates hypertension. This affects one third of the adult population and is the single leading cause globally of preventable heart attacks, strokes and deaths. A significant difference between the systolic blood pressure measurements in the two arms could be indicative of a narrowing, or a stiffening, of the arteries, which can affect blood flow. These arterial changes are recognised as a further risk marker for subsequent heart attack, stroke or early death, and should be investigated for treatment.

The researchers concluded that each mmHg difference found between the two arms, elevated predicted 10-year risk of one of the following occurring by one percent; new angina, a heart attack or stroke.

At the moment, both UK and European guidelines recognise a systolic difference of 15 mmHg or more between the two arms as the threshold indicative of additional cardiovascular risk. This new study found that a lower threshold of 10 mmHg was clearly indicative of additional risk, which would mean that far more people should be considered for treatment if such a difference between arms is present. To this end, the research team has created a tool that is easy for clinicians to use, to establish who should be considered for treatment based on their risk, incorporating the blood pressure reading in both arms.

Research co-author Professor Victor Aboyans, head of the department of cardiology at the Dupuytren University Hospital in Limoges, France, said "We believe that a 10 mmHg difference can now reasonably be regarded as an upper limit of normal for systolic inter-arm blood pressure, when both arms are measured in sequence during routine clinical appointments. This information should be incorporated into future guidelines and clinical practice in assessing cardiovascular risk. It would mean many more people were considered for treatment that could reduce their risk of heart attack, stroke and death."

An interarm difference of greater than 10 mmHg occurs in 11 per cent of people with high blood pressure (hypertension) - itself a known health risk - and in four per cent of the general population.

Children of mothers who drink relatively more cow's milk during breastfeeding are at reduced risk of developing food allergies. That is the conclusion of researchers from Chalmers University of Technology, Sweden, in a new study published in the scientific journal Nutrients.

The result is based on a survey of more than 500 Swedish women's eating habits and the prevalence of allergies in their children at one year of age.

"We have found that mothers of healthy one-year-olds consumed more cow's milk during breastfeeding than mothers of allergic one-year-olds. Though the association is clear, we do not claim that drinking cow's milk would be a general cure for food allergies." says Mia Stråvik, doctoral student in the Division of Food Science at Chalmers University of Technology, and first author of the study.

There are many factors behind the risk of food allergy, not least genetic predisposition. Yet, as Mia Stråvik explains, "Diet is a factor where parents themselves can have direct influence. It is quite common nowadays for young women to avoid drinking milk, due in part to prevailing trends and concerns, some of which are linked to myths about diet."

She points out that allergy to milk protein is uncommon in adults, so most women can consume milk and dairy products themselves without issue. Lactose intolerance is something completely different, when the body cannot break down milk sugars. And in this case, lactose-free dairy products are tolerated by the body.

The hygiene hypothesis

According to Professor Ann-Sofie Sandberg, Mia Stråvik's supervisor, one possible explanation may be that the milk in the mother's diet contains substances that stimulate the maturity of the immune system.

"In a child's early development, there is a time window where stimulation of the immune system is necessary for the child to develop tolerance to different foods."

According to something known as the hygiene hypothesis, early contact with various microorganisms can function as something of a kickstart' for a child's immune system, she explains.

"But, with the lower prevalence of microorganisms nowadays in our more hygienic society, substances taken in through the mother's diet can be another way to stimulate the maturity of the immune system."

Mia Stråvik's study is not the first to link cow's milk in a mother's diet to a reduced risk of allergies in children. Previous studies, however, have often been based solely on questionnaire responses - both in terms of eating habits and the presence of allergies. In this study both data and conclusions are significantly more robust.

"In this study, we were able to actually verify the women's reported intake of milk and milk products through biomarkers in her blood and breast milk. The biomarkers are two fatty acids formed in the cow's stomach, which are specific to dairy products," says Mia Stråvik. "Furthermore, all the cases of allergy in children were diagnosed by a doctor specialising in child allergies."

The study is part of a more extensive research project built around a family cohort study of 655 families who gave birth at Sunderby Hospital near Luleå, northern Sweden, during the years 2015 - 2018. The project was initiated, and the cohort established, by Ann-Sofie Sandberg from Chalmers, Professor Agnes Wold at the University of Gothenburg and the chief physician and paediatric allergist Anna Sandin, affiliated with Umeå University and Sunderby Hospital.

The current study is the first scientific publication, focusing mainly on allergies based on data collected from the families in northern Sweden.

A clear connection

The mothers in the study, more than 500, gave detailed accounts of their eating habits on three occasions - in the 34th week of the pregnancy, one month after the birth and four months after birth. At one year of age, the children were medically examined, and all cases of food allergy, atopic eczema and asthma were identified.

After the material was adjusted for various other factors, such as hereditary predisposition or reverse causation, the researchers were able to establish that there was indeed a clear connection between the mother's intake of milk and dairy products and the smaller incidence of food allergy in their children.

"No matter how we looked at and interpreted the data, we came to the same conclusion," states Chalmers researcher and co-author Malin Barman, Assistant Supervisor to Mia Stråvik."The mechanisms behind why milk has this preventative effect against allergies, however, are still unclear." A further explanation of various hypotheses can be found below.

Another result in the study that Mia Stråvik highlights is that children of breastfeeding mothers, who at the four month measurement were eating a lot of fruit and berries, tended to suffer from eczema to a much greater extent - though she stresses that further studies are needed before anything can be said with certainty about this connection.

A follow-up study is currently underway to examine the children's health at the age of four.

Read the article in the scientific journal Nutrients:

Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in O?spring

More about: Child allergies

Allergy is the most common chronic disease that affects children, and is becoming ever more prevalent in Sweden and other industrialised countries.

Of the 508 children included in the current study:

7.7 percent of the children (39) had a diagnosed food allergy at one year of age, most commonly to cow's milk or eggs (or both)

6.5 percent of the children (33) were diagnosed with atopic eczema and the same amount were diagnosed with asthma

23 percent of the children had allergies of some type (including non-food-based) at the age of one year

How does milk cause these effects?

It is unclear exactly why cow's milk in the mother's diet can reduce the risk of child allergy. According to researcher Malin Barman, there are several possible explanations, that could potentially work together.

"One hypothesis is that cow's milk contains something that activates the child's immune system and helps it to develop tolerance. This as-yet unknown cause could be found in the fat of the milk or in its protein content. But it could also be the case that the milk itself is neutral in relation to the immune system. Then it might be more simply a matter of a higher intake of milk fats leading to a relatively lower intake of polyunsaturated fats. This would help, because we believe high levels of polyunsaturated fat in a mother's diet can counteract the maturation of a child's immune system at an early age."

More about: The funding of this research

This research was funded by the Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare (Forte), Västra Götaland Region, Region Norrbotten, Magnus Bergvalls stiftelse, Wilhelm och Martina Lundgrens stiftelse, Per Håkanssons stiftelse, Stiftelsen Sigurd och Elsa Goljes Minne, The Royal Society of Arts and Sciences in Gothenburg and Jane och Dan Olssons stiftelse. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The authors declare no conflict of interest.

More about: the NICE project

The 655 families participating in the NICE cohort (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) were recruited during the years 2015-2018 in connection with pregnant women visiting Sunderby Hospital in northern Sweden.

The aim is to map how a number of factors in the nutritional intake of the foetus and infant affect their immune system and, in the long run, their health and development.

In addition to the connection between food and allergies, which is the Chalmers researchers' special area of responsibility, researchers are also looking at microorganisms and toxic substances and their significance for such things as dental health and neuropsychological development.

To this end, the researchers have built up an extensive biobank with samples from the participants - everything from placentas and umbilical cord blood to breast milk, urine and saliva.

Alongside Chalmers University of Technology, Umeå University, Karolinska Institutet and the University of Gothenburg are also participating in studies based on the NICE cohort - a total of around 30 researchers are involved.

A recent international observational study provides important data on the safety of head and neck cancer surgery during the COVID-19 pandemic. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society. The study is part of the COVIDSurg Collaborative, an initiative to describe surgical practices during the early period of the pandemic, when many hospitals had limited capacity and when it was unclear whether it was safer to delay or continue in-hospital cancer treatments.

"The problems were particularly acute in head and neck cancer surgery because for many cases, cure is dependent on surgery, but there was great concern about spreading infection from aerosol-generating procedures in the airway," said corresponding author Richard J. Shaw, MD, FDS, FRCS, of The University of Liverpool Cancer Research Centre, in the U.K.

Professor Shaw and his colleagues in the COVIDSurg Collaborative examined information on 1,137 patients with head and neck cancer undergoing potentially curative surgery in 26 countries. The most common sites were the oral cavity (38 percent) and the thyroid (21 percent). The death rate within 30 days after surgery was 1.2 percent, a rate that would be normally expected in this patient population, without a pandemic. Also, 29 (3 percent) patients tested positive for COVID-19 within 30 days of surgery; of these 13 (44.8 percent) developed severe respiratory complications and three (10.9 percent) died. According to Professor Shaw, clinicians now know that these risks can be minimized with precautions such as staff testing, infection control measures, and vaccination.

Patients were more likely to test positive for COVID-19 when they lived in communities with high levels of COVID-19, when they had oral tumors, and when they received a tracheostomy (an opening created in the neck to facilitate placing a tube into the windpipe).

"The early consensus was that head and neck surgery was very risky for patients, particularly less fit or elderly patients, or those who required complex procedures or reconstructive surgery," Professor Shaw said. "Our data are reassuring in this regard, showing that there is no additional risk of COVID-19 for these groups."

The investigators noted that insights from the study are especially important now, as many regions are experiencing a second wave of COVID-19 spread. "Data from the COVIDSurg Collaborative have clarified the measures required to make cancer surgery safe, and critically, to inform priorities for both patients and healthcare systems," said Professor Shaw. "For patients with head and neck cancer, the tumors present a much greater threat to life than the risk of developing COVID-19, assuming precautions are taken."

Testing for COVID-19 has been central in the fight against SARS-CoV-2/ COVID-19. While most efforts, including regulations, have focused on testing as a clinical medical diagnostic tool, the most powerful forms of testing to help control the pandemic have rarely been used or recognized, according to Michael Mina, MD, PhD. In a perspective piece published in Science, Mina and his co-author, Kristian G. Andersen, PhD, describe the power of public health screening, which focuses on mitigating transmission of the virus at the population level, and how it may be a crucial and overlooked tool.

"The way that this screening works is to have enough people test themselves frequently - say, twice per week - ideally using rapid tests," said Mina. "By empowering people with the knowledge of their transmission status, we can effectively slow transmission down at the overall community level."

The authors also discuss the role of "entrance screening," in which individuals are screened upon entry into a location like an office, work, restaurant, etc.

"When coupled with public health screening, entrance screening can add another layer of protection and together it could allow the economy to open up more readily," said Mina.