Body

Ask Eric Weaver about pandemics, and he's quick to remind you of a fact that illustrates the fleeting nature of human memory and the proximal nature of human attention: The first pandemic of the 21st century struck not in 2019, but 2009.

That's when the H1N1/09 swine flu emerged, eventually infecting upwards of 1.4 billion people -- nearly one of every five on the planet at the time. True to the name, swine flus jump to humans from pigs. It's a phenomenon that has been documented more than 400 times since the mid-2000s in the United States alone.

"They're considered the great mixing vessel," said Weaver, associate professor of biological sciences at the University of Nebraska-Lincoln. "They're susceptible to their own circulating influenzas, as well as many of the avian and human influenzas.

"If you put an avian, a swine and a human virus into the same cell, they can swap genome segments. When you mix those viruses in the swine, what pops out could be all swine, or a little human and swine, or a little avian and swine, or a little of all three. And you never know: You might get the perfect combination of parts that makes for a very high-fitness virus that is highly transmissible and new to humans, meaning that people don't have immunity to it."

All of it helps explain why Weaver has spent years researching how to develop a vaccine that protects against as many strains of influenza as possible, including those that have yet to emerge. In a new study, Weaver, doctoral candidate Brianna Bullard and colleagues have debuted the results of an approach that demonstrates promising signs of protection against more than a dozen swine flu strains -- and more than a leading, commercially available vaccine.

"This is the best data I've ever seen in the (research) literature," Weaver said of the team's findings, recently published in the journal Nature Communications.

The "H" and "N" in H1N1 refer to two crucial proteins, hemagglutinin and neuraminidase, that reside on the surface of influenza viruses and allow them to enter and exit cells. But it's the H3 subtype of influenza -- H3N2, specifically -- that has accounted for more than 90% of swine-to-human infections in the United States since 2010, making it the target of Weaver's most recent research.

In his efforts to combat multiple strains of swine H3N2, Weaver employed a computational program, Epigraph, that was co-developed by Bette Korber of Los Alamos National Laboratory. The "epi" is short for epitope: the bit of a viral protein, such as hemagglutinin, that draws the attention of an immune system. Any one epitope, if administered as a vaccine, will stimulate an immune response against only a limited number of closely related viral strains.

So Weaver put Epigraph to work analyzing data on every known and available mutational variant of hemagglutinin, which it then used to predict which collection of epitopes would grant immunity against the broadest, most diverse range of strains. Those hemagglutinin proteins are usually composed of around 560 amino acids, whose type and sequence determine the structure and function of the epitopes. Starting at the start of an amino acid string, Epigraph analyzed the sequence of amino acids No. 1 through No. 9 before sliding down to analyze Nos. 2-10, then 3-11, and so on. After doing the same for every epitope, the program determined the most common nine-acid sequences from the entire batch -- the entire catalogue of known H3N2 strains in pigs.

"So what you end up with are the most common epitopes that exist in nature linked together, then the second-most common, and then the third-most common," Weaver said. "When you look at it from an evolutionary standpoint, the first resembles what most of the viruses look like. The second starts to look a bit different, and the third looks even more different.

"But all three of these make a contribution to the vaccine itself, and they work through slightly different mechanisms."

When testing the resulting three-epitope cocktail in mice and pigs, the team found that it yielded immune response signatures and physiological protection against a much wider variety of strains than did FluSure, a commercial swine vaccine.

In mice, the team tested its vaccine against 20 strains of swine-derived H3 flu. The vaccine generated clinically relevant concentrations of antibodies -- the molecules that neutralize a virus before it enters a cell -- against 14 of those 20 strains. FluSure managed the same feat against just four of the 20. A separate experiment presented the mice with four strains that represented a cross-section of H3 diversity. In all four cases, Epigraph-vaccinated mice produced notable levels of T-cells, which, among other responsibilities, instruct infected cells to die for the sake of avoiding further viral transmission. FluSure-vaccinated mice, by contrast, showed little T-cell response to any of the four strains.

Those cellular-level responses appeared to scale up, too. When challenged with flu viruses, Epigraph-vaccinated mice generally lost less weight, and exhibited fewer viral particles in the lungs, than did their FluSure-vaccinated counterparts. And when mice were challenged with a lethal H3 strain derived from humans, only the Epigraph vaccine protected all of the specimens that received it.

That performance carried over to pigs. Cells taken from swine injected with just one dose of the Epigraph vaccine produced substantial antibodies in response to 13 of 20 H3 strains, including 15 of 16 that originated in North America or were derived from humans. A single dose of FluSure, meanwhile, generated significant antibodies against none of the 20. Though a second dose of FluSure did elevate those antibody concentrations, they remained about four times lower, on average, than the Epigraph-induced responses. T-cell responses, too, remained higher in Epigraph-vaccinated pigs.

More, and more-generalizable, experiments will be needed to verify the Epigraph vaccine's performance, Weaver said. For one, the team is looking to test whether the vaccine candidate generates actual immunity in living pigs, beyond the promising immune responses from their cells in a lab. There's also the matter of determining how long any immunity might last.

But Weaver has already developed a human equivalent of the swine flu vaccine cocktail that he's likewise preparing to test. Considering the similarities between flu infections in humans and pigs -- susceptibilities to subtypes, clinical symptoms, even viral receptors in respiratory tracts -- he said the recent findings bode well for those future, human-centric efforts. Success on that front could eventually mean pivoting away from the current approach to flu vaccinations, whereby virologists are forced to predict which strains will dominate a flu season -- and, despite their best efforts, sometimes miss the mark.

"This study is equivalent to a bench-to-bedside study, where the positive results in the preclinical mouse study are confirmed by positive results in a clinical pig study," Weaver said. "This gives us confidence that when the concept is applied to human influenza virus, we'll see the same translation from preclinical studies to clinical studies in humans."

Semaglutide, an injectable medication taken once a week, offers a nonsurgical way to reduce weight and treat obesity. It could help the more than 70 million adults in the United States who struggle with this chronic condition, says Ildiko Lingvay, M.D., M.P.H., M.S.C.S., professor of internal medicine and population and data sciences at UTSW and lead author of the study, published today in The Lancet.

People with diabetes benefit greatly from weight loss, yet they have a much harder time losing weight compared with those without diabetes, Lingvay says. This study is the first to evaluate the weight loss effect of this medication exclusively in patients with Type 2 diabetes.

This multicenter study was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa, and Asia from June 2018 to June 2020. It is one of the studies conducted as part of the Semaglutide Treatment Effect for People (STEP) with obesity program. "In the four clinical trials completed so far, people treated with this medication lost on average 10 to 17 percent of their body weight, which is a huge step forward compared with all other medications currently available to treat obesity," says Lingvay. "With this drug, results are getting close to what we see with bariatric surgery, which is 20 to 30 percent weight loss."

Medications from this drug class have been used for more than a decade to treat people with diabetes. Semaglutide is currently approved by the Food and Drug Administration to lower blood sugar in people with diabetes at a dose of 0.5 mg or 1 mg once weekly. The FDA is evaluating use of a higher weekly 2.4 mg dose for chronic weight management.

The STEP 2 study, a randomized, double-blind, double-dummy, placebo-controlled phase 3 clinical trial reported in The Lancet, involved more than 1,200 adults with Type 2 diabetes who were overweight or obese at the time. Over 68 weeks, they injected semaglutide or a placebo once a week. A body mass index (BMI) over 30, or a BMI over 27 along with other comorbidities, was required to participate.

"In this study, more than a quarter of participants lost over 15 percent of their body weight, which is by far the best result we had with any weight loss medicine in patients with diabetes," she says.

Other STEP trials investigating a weekly dose of semaglutide 2.4 mg in obese adults without diabetes reported even greater weight loss of 15 to 16 percent body weight.

The drug works by suppressing appetite centers in the brain to reduce caloric intake, Lingvay adds.

"The medication continually tells the body that you just ate, you're full," she says.

Participants took the subcutaneous injection with a pre-filled pen and tiny needle once a week. They also met with a registered dietitian to help them follow a reduced calorie meal plan.

Average weight loss among participants treated with semaglutide 2.4 mg was 21.4 pounds, compared with 7.7 pounds in the placebo group. About 69 percent of participants treated with semaglutide 2.4 mg lost 5 percent or more of their body weight, which can improve comorbidities such as high blood pressure. Half of those taking semaglutide 2.4 mg achieved weight loss of 10 percent or more, and 25 percent attained weight loss of 15 percent or greater.

For someone with diabetes, losing weight can be especially challenging.

"People with diabetes lose much less weight than their peers without diabetes," Lingvay says. "For people with diabetes, a 10 percent weight loss is a phenomenal accomplishment."

The drug is recommended for lifelong use and is not intended to be stopped once weight loss is achieved, she adds.

"Obesity is a chronic medical condition," Lingvay says. "It is not something you treat like the flu."

Home health visits change to virtual ones during pandemic

'We don't have to rely on mental health professionals'

As perinatal depression soars during pandemic, there's a growing need for treatment

CHICAGO --- Perinatal depression has soared during the pandemic. But many mental health professionals are overwhelmed and can't take on new clients.

Good news comes from a new Northwestern Medicine study finding paraprofessionals generated similar reductions in depressive symptoms as mental health professionals when delivering a group-based cognitive-behavioral therapy intervention.

The study findings are based on adding home health visits by trained lay health professionals to low-income pregnant women in a national project called Mothers & Babies. Mothers and Babies is an intervention using cognitive behavioral therapy that aims to reduce stress and improve mood among pregnant women and new mothers.

But since in-person home-visits are no longer possible during the pandemic, the program has recently pivoted to deliver the therapy virtually to pregnant women.

"The response to Mothers and Babies delivered virtually has been incredibly positive from providers and clients," said lead study author Darius Tandon, associate professor of medical social sciences at Northwestern University Feinberg School of Medicine. "In this COVID environment, the need for mental health services is so great that providers and perinatal women who have stress in their lives are really valuing the ability to receive help remotely."

One in five women will develop postpartum depression, and both mother and child are adversely affected by postpartum depression.

"Preventing postpartum depression before it starts is critical in promoting the health and well-being of new mothers and their children," Tandon said.

"With appropriate training and supervision, lay health workers can do a good job," Tandon noted. "We don't have to rely on mental health professionals. We can go another route."

The paper will be published March 3 in Archives of Women's Mental Health.

This is the first study to the researchers' knowledge that has used lay home visitors to deliver a postpartum depression preventive intervention. Previous studies using lay health workers have focused on postpartum depression treatment.

Researchers say there is a growing interest in the notion of "task shifting", or moving care from more specialized (e.g., mental health professionals) to less specialized health workers.

"This study suggests that it is possible to 'task shift' the delivery of interventions aimed at preventing postpartum depression to paraprofessional home visitors, said Tandon, who is also co-director of the Center for Community Health at Feinberg. "This is notable given the lack of available mental health professionals in many communities, as well as stigma associated with seeing 'formal' mental health providers."

The use of paraprofessional home visitors - rather than costlier mental health professionals -- also may minimize cost associated with delivering interventions, he noted.

Positive psychological effects associated with taking small doses of psychedelic drugs are likely the result of users' expectations, suggests a study published today in eLife.

The study - the largest placebo-controlled trial on psychedelics to date - used an innovative 'self-blinding citizen science' approach, where members of the public who were already microdosing implemented their own placebo control following online instructions. The results from the trial may influence future studies in real-world settings.

There has been renewed interest in studying whether psychedelic drugs may be a useful treatment for depression, addiction, obsessive-compulsive disorders and other conditions. Few small studies have previously suggested that microdoses - small doses of psychedelic drugs taken one to three times a week - may improve people's wellbeing, creativity and overall cognitive performance. But many of the studies lack a control group of participants taking a dummy pill to determine if these positive outcomes are the result of the drug's action, or the result of the participants' expectations of a benefit - the so-called placebo effect. "Anecdotal reports about the benefits of microdosing are almost certainly biased by the placebo effect," says lead author Balázs Szigeti, a research associate at Imperial College London, UK.

Szigeti and his colleagues designed a citizen science study where individuals who were already microdosing could participate online. First, the 191 participants followed a setup procedure that mixed placebo pills with microdose ones. After the setup, the participants had a set of capsules without knowing which were placebo and which were microdose. The authors call this process 'self-blinding', as participants lost knowledge of which drug they were taking. The setup included barcodes which, when scanned, linked to the study's IT infrastructure and allowed the researchers to track who had taken microdoses or placebos. The participants then filled out surveys about their experiences and completed online cognitive tests, while they took the pills over a four-week period.

Participants who were taking the real psychoactive drugs and those unknowingly taking the placebos reported similar psychological benefits. "Our results are mixed: on the one hand, we observed microdosing's benefits in a wide range of psychological measures; on the other hand, equal benefits were seen among participants taking placebos," Szigeti explains. "These findings suggest that the benefits are not due to the drug, but rather due to the placebo-like expectation effects. Many participants who reported that they experienced positive effects while taking the placebo were shocked to learn after the study that they hadn't been taking the real drug."

The authors caution that the results are not as reliable as the results from a traditional placebo-controlled study, due to participants sourcing their drug from the black market. However, the team's citizen science approach accurately reflects 'real-life microdosing' - that is, how microdosing is done in practice. Additionally, the study cost a fraction of what a traditional clinical study would cost, which may make it a useful first step in assessing whether other popular phenomena can be explained by the placebo effect.

"The successful execution of this study could inspire similar studies in a broad range of scientific or medical contexts," says senior author David Erritzoe, Clinical Senior Lecturer in Psychiatry at Imperial College London. "Accounting for the placebo effect is important when assessing trends such as the use of cannabidiol oils, fad diets or supplements where social pressure or users' expectations can lead to a strong placebo response. Self-blinding citizen science initiatives could be used as an inexpensive, initial screening tool before launching expensive clinical studies."

In a new study from Shiley Eye Institute at UC San Diego Health, researchers have identified a potential new marker that shows cardiovascular disease may be present in a patient using an optical coherence tomography (OCT) scan -- a non-invasive diagnostic tool commonly used in ophthalmology and optometry clinics to create images of the retina. The finding suggests it may be possible to detect heart disease during an eye examination.

In the paper published March 2, 2021 in EClinical Medicine by The Lancet, the research team examined lesions of the retina, the inner-most, light-sensitive layer of the eye, to determine if a cardiovascular disorder may be present.

"The eyes are a window into our health, and many diseases can manifest in the eye; cardiovascular disease is no exception," said lead author Mathieu Bakhoum, MD, PhD, a physician-scientist and retina surgeon at UC San Diego Health. "Ischemia, which is decreased blood flow caused by heart disease, can lead to inadequate blood flow to the eye and may cause cells in the retina to die, leaving behind a permanent mark. We termed this mark 'retinal ischemic perivascular lesions,' or RIPLs, and sought to determine if this finding could serve as a biomarker for cardiovascular disease."

As part of the study, the team reviewed the records of individuals who received a retinal OCT scan at UC San Diego Health from July 2014 to July 2019. From that cohort, two groups were identified after medical chart review: one consisted of 84 individuals with heart disease and the other included 76 healthy individuals as the study's control group. An increased number of RIPLs was observed in the eyes of individuals with heart disease.

According to the researchers, the higher number of RIPLs in the eye, the higher the risk for cardiovascular disease.

"The only way we can visualize the smallest blood vessels in the body is in the eye. The retina in particular provides important evidence of the adverse effects of cardiovascular issues, such as high blood pressure," said Anthony DeMaria, MD, Judith and Jack White Chair in Cardiology and cardiologist at UC San Diego Health. "It's my hope that the presence of RIPLs in the eye will serve as a marker for cardiovascular disease when patients are undergoing assessment of risk factors for heart disease, or when patients are undergoing evaluation for the suspected presence of heart disease."

DeMaria said detection of RIPLs could result in identification of cardiovascular disease that would enable early therapy and preventative measures, and potentially reduce numbers of heart attacks or strokes.

A person's risk for cardiovascular disease is determined by the atherosclerotic cardiovascular disease (ASCVD) risk score calculator, the national guideline developed by the American College of Cardiology. The guideline is considered the gold standard for assessing a patient's 10-year risk of experiencing a cardiovascular event, such as heart attack or stroke. In the study, researchers found a correlation between the number of RIPLs in a patient's eye and their ASCVD risk score.

"Individuals with low and borderline ASCVD scores had a low number of RIPLs in their eyes, but as the ASCVD risk increased, so did the number of RIPLs," said Bakhoum.

Ophthalmologists at UC San Diego Health now consider referring patients to a cardiologist if RIPLs are identified during an OCT scan. The research teams hopes this paper and future studies will result in RIPLs becoming a common ophthalmological marker for identifying potential cardiovascular disease, and incorporated into the overall ASCVD risk score.

"Globally, cardiovascular disease is the number one cause of death and unfortunately many people are unaware they may have heart issues," said Bakhoum. "The key in preventing this is early detection and treatment. It's our hope that by identifying RIPLs as a marker for cardiovascular disease providers will be able to identify heart issues before a catastrophic event, such as a heart attack or a stroke, occurs."

Patients with type 2 diabetes that were treated with a weekly injection of the breakthrough drug Semaglutide were able to achieve an average weight loss of nearly 10kg, according to a new study published in The Lancet today.

Led by Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and the Co-Director of the Leicester Diabetes Centre, the study showed that two thirds of patients with type 2 diabetes that were treated with weekly injections of a 2.4mg dose of Semaglutide were able to lose at least 5% of their body weight and achieved significant improvement in blood glucose control.

More than a quarter of patients were able to lose more than 15% of their body weight - far above that which has been observed with any other medicine administered to people with diabetes.

Professor Melanie Davies said:

"These results are exciting and represent a new era in weight management in people with type 2 diabetes - they mark a real paradigm shift in our ability to treat obesity, the results bring us closer to what we see with more invasive surgery.

"It is also really encouraging that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure and blood glucose control".

This global multi-centre trial was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa and Asia, involving 1,210 patients with type 2 diabetes whose current treatment was not achieving sufficient blood sugar control, for instance through diet and exercise, or through the use of metformin and other glucose lowering medicines used to control the disease.

It is one of a portfolio of studies conducted as part of the Semaglutide Treatment Effect for people with obesity Programme (STEP) programme. Professor Davies has been involved in all four of the STEP clinical trials involving Semaglutide for weight management completed so far, where the medication was shown to help patients achieve an average weight of loss of between 10kg and 17kg of body weight.

Being overweight or obese is a significant contributor to type 2 diabetes. Many patients can manage their type 2 diabetes by eating a healthy diet, taking regular exercise, and using medications to help control blood sugar, or achieve glycemic control but for a significant minority of patients who have not seen much improvement in spite of these methods, semiglutide is a promising development.

The LDC has a world-renowned, multi-disciplinary research team, which is leading the way and providing the evidence behind the Leicester Diabetes Centre's education programmes and widening the knowledge base for health and disease management.

Type 2 diabetes, once considered an adult disease, is increasingly causing health complications among American youth. A research review published in the Journal of Osteopathic Medicine suggests physicians should work to more aggressively prevent pediatric diabetes.

Because few pediatric Type 2 diabetes treatment options are available, prevention is unusually important. To improve health outcomes, the paper's authors recommend physicians conduct regular screenings of children and adolescents, adopt a high level of suspicion, and intervene early and often with families who have children at risk for prediabetes and T2 diabetes.

"Pediatric type 2 diabetes is more progressive and aggressive than adult-onset Type 2 diabetes," said lead author Jay H. Shubrook, DO, professor and diabetologist at Touro University California College of Osteopathic Medicine. "Kids need our help, and we're not sounding the alarm loud enough."

Risk factors

A young person's metabolism is different than that of an adult. The liver does not clear insulin at the same rate, and youths experience a more rapid decline in β-cell function--meaning they lose the ability to produce enough insulin more quickly than adults.

For young people who struggle with their weight, diabetes is a significant risk. Excessive weight can lead to insulin resistance, a turning point for the disease. The National Health and Nutrition Examination Survey, a national study that published in 2018 and again in 2020, found that the rate of obesity in youth was 18.5% and that prediabetes was found in 18% of adolescents.

"That the rates of youth obesity and prediabetes are nearly the same is not a coincidence," said Dr. Shubrook.

Managing the disease

Childhood obesity is a complex problem that extends beyond the health behaviors of a child.

The American Diabetes Association recommends considering food insecurity, housing instability, and potential financial limitations when working with families to create a plan to manage the disease. Stress, isolation, depression, anxiety, substance abuse, and eating disorders should be screened for during the evaluation and treatment process.

"The best chance at slowing the youth diabetes epidemic is for physicians to identify at-risk youths and provide early interventions that emphasize family-based preventive lifestyle changes," said Dr. Shubrook. "Osteopathic principles and practice, which incorporate a patient's environmental, societal, and lifestyle factors into care, support this process."

Pregnant patients in Colorado may be told about parenting and adoption, but not abortion. This is according to a new study led by Kate Coleman-Minahan of the University of Colorado College of Nursing published in the Journal of Midwifery and Women's Health.

"Access to abortion is a public health priority," said Coleman-Minahan, assistant professor at the CU College of Nursing and lead author of the study. "Evidence-based and nonjudgmental counseling on all three pregnancy options (abortion, adoption and parenting) support individual autonomy and the health and well-being of pregnant patients and their families."

While pregnant women want to know all of their options, the study found only 48% of clinicians were willing and able to give them complete, accurate and unbiased information. The staff involved included nurse practitioners, nurse midwives and physician assistants, not the doctors.

The reasons for being unwilling or unable to counsel vary. The study found some clinicians oppose abortion rights, while others' organizations don't allow them to bring it up in discussion. However, the biggest reason for withholding the information is a lack of knowledge and training. A surprising 79% of the clinicians who are unable to counsel on abortion say they don't have the experience or education to counsel women about abortion.

"The data identify a knowledge gap among Colorado clinicians and suggest a need for more training in pregnancy options counseling and abortion referrals," said Coleman-Minahan.

The study found 53% of clinicians refer patients for abortion care and 31% refer to crisis pregnancy centers. Crisis pregnancy centers, or pregnancy resource centers, try to dissuade women from choosing abortion.

Major U.S. professional health, medical and nursing organizations recommend informed counseling so that women can make voluntary decisions and access timely abortion care. They also recommend against referring to crisis pregnancy centers.

OAK BROOK, Ill. - Attendance at regular mammography screening substantially reduces the risk of dying from breast cancer, according to a large study of over half a million women, published in the journal Radiology. Researchers said women who skip even one scheduled mammography screening before a breast cancer diagnosis face a significantly higher risk of dying from the cancer.

Breast cancer screening with mammography has helped reduce disease-related deaths by enabling detection of cancer at earlier, more treatable stages. Despite mammography's well-established effectiveness, many women don't participate in recommended screening examinations.

In the new study, led by László Tabár, M.D., from Falun Central Hospital in Falun, Sweden, and funded by the American Cancer Society, a multinational team of researchers took a more detailed look at screening attendance patterns to further refine mortality risk estimates. They analyzed data from almost 550,000 women eligible for mammography screening in nine Swedish counties between 1992 and 2016. The women were divided into groups based on their participation in the two most recent scheduled screening exams prior to cancer diagnosis. Women who participated in both screening sessions prior to diagnosis were identified as serial participants, while those who did not attend either screening opportunity were categorized as serial nonparticipants.

Analysis showed that participation in the two most recent mammography screening appointments before a breast cancer diagnosis provides a higher protection against breast cancer death than participation in neither or only one examination.

The incidence of breast cancers proving fatal within 10 years of diagnosis was 50% lower for serial participants than for serial nonparticipants. Compared to women who attended only one of the two previous screens, women who attended both had a 29% reduction in breast cancer mortality.

"Regular participation in all scheduled screens confers the greatest reduction in your risk of dying from breast cancer," said the study's lead author, Stephen W. Duffy, M.Sc., professor of cancer screening at Queen Mary University of London.

Duffy said the results add further evidence to support regular screening with mammography as a means for reducing breast cancer-related deaths.

"While we suspected that regular participation would confer a reduction greater than that with irregular participation, I think it is fair to say that we were slightly surprised by the size of the effect," Duffy said. "The findings support the hypothesis that regular attendance reduces the opportunity for the cancer to grow before it is detected."

The researchers are continuing to study mammography data to develop a more comprehensive picture of screening benefits, including the impact on interval cancers that arise between screening mammography examinations.

"We are planning further prognostic research into the mechanism of this effect," Duffy said. "For example, we plan to investigate whether and--if so--to what extent regular attendance improves the prognosis of interval cancers as well as screen-detected cancers. Estimation of this by time since last screen may have implications for policy on screening frequency."

[LAKEWOOD, CO; BRIDGEWATER, NJ; March 2, 2021] Two of the world's leading veterinary organizations are proud to announce updated recommendations in the 2021 AAHA/AAFP Feline Life Stage Guidelines. The American Animal Hospital Association (AAHA) and the American Association of Feline Practitioners (AAFP) convened a Task Force of experts in feline medicine to define distinct feline life stages and provide a framework for individualized healthcare plans.

Understanding a cat's life stage and lifestyle greatly impacts healthcare strategies. Veterinary professionals have a responsibility to stress the need for ongoing care for feline patients at every stage of their lives. The updated Guidelines detail the evolution of feline biology and lifestyle over time, requiring different approaches to healthcare for kittens and senior cats.

The Guidelines outline four age-related life stages, with the fifth, end-of-life stage, occurring at any age.

Feline Life Stages

Kitten: Birth up to 1 year

Young adult: 1 to 6 years

Mature adult: 7 to 10 years

Senior: 10 years and older

End-of-life: Any age

The Guidelines combine feline-friendly care approaches with a lifelong healthcare plan to improve health and wellbeing. "A cat-friendly approach tailored to the individual patient creates a more positive experience for the patient, client, and care provider, and promotes more frequent visits and improved compliance," stated Task Force Co-Chair, Jessica Quimby, DVM, Ph.D., DACVIM.

Quick reference tables are included in the Guidelines to aid veterinary professionals in developing evolving care plans that grow with cats as they age. "All cats of every life stage need full, thorough physical examinations at least annually for the best lifelong care; and we recommend checkups at a minimum of every six months for senior cats," said AAHA Chief Medical Officer Heather Loenser, DVM. "The Guidelines provide discussion items and medical history questions for all life stages, as well as life stage-specific focal points for physical examinations, claw care, litter box management, nutrition, behavior, oral health, enrichment, and vaccinations."

Additionally, for veterinary teams, the Feline Lifestyle Assessment Form helps gather a deeper history for each cat. This form makes it easier to tailor the physical examination and to identify specific questions and discussions based on the client's feedback.

Philadelphia, March 2, 2021 - Researchers from the Mitochondrial Medicine Frontier Program at Children's Hospital of Philadelphia (CHOP) have demonstrated how one combination of therapies may be beneficial for patients with mitochondrial respiratory chain disorders. This preclinical research paves the way to develop more tailored treatment options for patients with inherited mitochondrial disease and acquired energy disorders. The findings emphasize the importance of rational therapeutic modeling to target specific cellular deficiencies and provide proper cellular nutrition as an effective means to manage mitochondrial disease.

The findings were published online by the journal Human Molecular Genetics.

Mitochondrial disease describes a collective group of energy deficiency disorders with no FDA-approved treatments or cures. Approximately 350 different gene disorders have been shown to substantially impair mitochondrial respiratory chain function, an essential process for making energy to power our cells. Respiratory chain function can also become severely disrupted by other genetic conditions, certain medications or environmental exposures, as well as common metabolic disorders, strokes, heart attacks, the aging process, and Alzheimer and Parkinson's diseases.

In the absence of FDA-approved therapies, many affected patients seek out or are prescribed a wide variety of vitamins, supplements, and enzyme cofactors or "helper molecules" that generally fall into three different treatment classes: antioxidants, metabolic modifiers, and signaling modifiers. However, rigorous clinical trials have not been performed for these compounds to guide the medical community in understanding their comparative safety or benefit in mitochondrial disease patients. Additionally, prior to this study, it was unknown whether the best options were to give specific therapies alone or whether a combination of therapies are actually safe to administer and may work synergistically to provides patients with any direct health benefit.

"We wanted to test unique combinatorial treatment regimens in preclinical models of mitochondrial disease to determine whether they showed any objective and measurable benefit to health, and to learn whether some combinations may be more effective than others," said senior study author Marni Falk, MD, Professor in the Division of Human Genetics as well as attending physician and Executive Director of the Mitochondrial Medicine Frontier Program CHOP. "This modeling approach would show us where physiology is most improved and take the guesswork out of developing treatment options for our patients."

The study team, including Mitochondrial Medicine team members Sujay Guha, PhD and Neal D. Mathew, PhD, used two translational animal models of mitochondrial respiratory chain complex I disease - the most common biochemical site of dysfunction in mitochondrial disease - to evaluate 11 random combinations of drugs selected from each of the three treatment classes. Of those combinations, only one combination - glucose, nicotinic acid, and N-acetylcysteine - synergistically improved the lifespan of the first model beyond any individual component alone, as well as mitochondrial membrane potential, a quantitative measurement of how well mitochondria perform their essential energy-producing function. Importantly, this combination treatment yielded these survival and cellular physiology improvements without exacerbating any negative side effects, such as oxidative or mitochondrial stress. Validation studies performed in the second model, zebrafish, showed that glucose, nicotinic acid, and N-acetylcysteine combination therapy prevented stress-induced brain death - a sign that this therapy may prevent metabolic strokes such as those that occur with stress in Leigh syndrome and other mitochondrial disease syndromes - and rescued larval zebrafish animal swimming capacity as well as their tissue levels of ATP and glutathione.

"The variable combinations of therapies used to manage mitochondrial disease patients tend to include empirically-based 'cocktails' of vitamins and nutrients whose safety and efficacy are difficult to objectively evaluate and compare," Falk said. "Our preclinical study demonstrates that identifying the right combination of therapies that is rationally-designed based on addressing the unique cellular deficiencies of major mitochondrial disease classes can provide clear, measurable survival and health benefits over individual therapies that each address only part of the cellular problem. It is important to translate these research insights into future clinical studies that test whether these optimized combinational therapy regimens improve health and provide resiliency to prevent clinical disease progression in mitochondrial disease patients."

BOSTON - Lymph nodes in the armpit area can become swollen after a COVID-19 vaccination, and this is a normal reaction that typically goes away with time. Radiologists at Massachusetts General Hospital (MGH) who recently published an approach to managing this situation in women who receive mammograms for breast cancer screening in the American Journal of Roentgenology have now expanded their recommendations to include care for patients who undergo other imaging tests for diverse medical reasons. Their guidance is published in the Journal of the American College of Radiology.

"Our practical management plan extends the impact of our recommendations to the full spectrum of patients having imaging tests after vaccination," says lead author Constance Lehman, MD, PhD, chief of Breast Imaging, co-director of the Avon Comprehensive Breast Evaluation Center at MGH, and professor at Harvard Medical School.

Lehman and her colleagues--from multiple subspecialties in radiology--note that as COVID-19 vaccination programs ramp up, radiologists should expect to see increasing numbers of patients who show swollen lymph nodes on imaging exams. They recommend that imaging centers document COVID-19 vaccination information--including the date(s) of vaccination, the location of the injection site, and the type of vaccine--on all patient forms and ensure that this information is easily available to radiologists at the time the image is interpreted.

In most cases, no additional imaging tests are needed for swollen lymph nodes after recent vaccinations unless the swelling persists or if the patient has other health issues. Additional tests may be warranted in cases where there was a heightened concern for cancer in the lymph nodes before the imaging test was performed. "In a patient with a recent cancer diagnosis, the patient's full care team and the radiologist can work together to determine how best to manage nodes that appear abnormal on imaging after a recent vaccination. That way, they can tailor care to the individual patient," says Leslie Lamb, MD, breast imaging specialist at MGH and co-author of the study.

Radiologists' communication with clinicians and patients should stress the importance of avoiding delays in either vaccinations or recommended imaging tests to ensure their optimal care throughout the pandemic. "Advanced planning can support our patients to feel confident and safe to receive their vaccinations as well as undergo recommended imaging in their usual care," says Lehman.

The team's management recommendations will continue to be updated as more data are available to guide best practice.

BINGHAMTON, NY - Several proposals have emerged on how to distribute the COVID-19 vaccine, but they fall short in ensuring that the vaccine is distributed fairly. A team including Binghamton University professor Nicole Hassoun suggests three ways to more fairly and effectively distribute the vaccine so that people in poor countries get the vaccine as soon as possible.

"Although many people in rich countries will receive a vaccine for COVID-19 this year, many people in poor countries will likely have to wait years to get one," said Hassoun. "Ethical vaccine allocation requires closing this gap and ensuring that everyone can access a vaccine as soon as possible. We should increase vaccine manufacturing, distribution and uptake. Rich countries should not get to prioritize their populations first."

Several proposals have emerged offering guidelines for how to distribute the COVID-19 vaccine fairly. These include the COVID-19 Vaccines Global Access (COVAX) facility, a collaboration that brings together governments, companies, international organizations, and others to accelerate the development and manufacture of COVID-19 vaccines. Currently, COVAX is set up so that in a first phase poor countries can vaccinate 3% of their populations, while rich countries can vaccinate up to 50%. Another sophisticated proposal, the "Fair Priority" model, suggests countries with vaccines contribute to global distribution once their COVID-19 transmission rates drop below 1.

However, insofar as the aim is to have the greatest health impact, these proposals fall short, according to Hassoun and her team. They offer three suggestions:

1. Proposals for fair distribution must address health problems for individuals. Moreover, since most individuals have little choice as to their country of origin or residence, we should not discriminate against them based on location. A fair proposal cannot allow rich countries to hoard vaccines or prioritize their own populations first. Nor can it give individuals' less priority simply because they live in a country with less infrastructure, capacity, or willingness to distribute vaccines.

2. Allocation principles must explicitly focus on both direct and indirect health effects of COVID-19. Direct health effects include death and disability caused (in full or in part) by the virus. Indirect health effects include death and disability caused (in full or in part) by the social response to the virus.

3. Having greatest global health impact requires assisting countries in their vaccine distribution, production, and consumption. A fair allocation system must consider how vaccine distribution will determine the success of whatever strategy is adopted.

"Many proposals for equitable allocation let rich countries prioritize their populations," said Hassoun. "We must combat this scarcity mindset and expand access rather than just shift resources around."

Additional researchers contributing to this paper include Anders Herlitz, Zohar Lederman, Jennifer Miller, Caesar Atuire, Lisa Eckenwiler, Sridhar Venkatapuram, and Marc Fleurbaey.

The paper, "Just Allocation of COVID-19 Vaccines," was published in BMJ Global Health.

Breast cancer is the commonest fatal cancer in women. Early detection increases a woman's chances of recovery. Magnetic Resonance Imaging (MRI) is an accurate technique for detecting and classifying tumours in breast tissue. However, it sometimes causes "false alarms", thus requiring further investigation (biopsy) and in some cases even resulting in so-called overtreatment, that is to say unnecessary surgery. For the first time, a research team from MedUni Vienna has now confirmed a threshold value for a non-invasive imaging biomarker. This can be incorporated into short standard MRI scans and could reduce the biopsy rate following MRI scans by 30%. Since the infrastructure for this measurement already exists in every radiological facility in Austria, the biomarker could be immediately deployed countrywide.

MRI for early detection, where there is an elevated breast cancer risk, or to complete diagnosis in the event of an unclear mammogram, is the most accurate method for diagnosing breast cancer. But this comes at a price: in one to two out of every ten women, there is a false alarm due to tissue changes that resemble breast cancer on the MRI scan. A biopsy of the breast tissue is then taken for diagnostic purposes, to rule out the presence of cancer. For many women, these biopsies cause considerable physical and emotional stress, as well as generating additional costs. A study conducted by a multi-centre and multi-national working group led by MedUni Vienna has now shown that a particular threshold value (ADC) in a special MRI technique, diffusion-weighted imaging (DWI), can indicate whether or not it is necessary to take a biopsy from the suspected lesion. In future, this could avoid one third of unnecessary biopsies following MRI.

Immobile and "dancing" molecules

MRI uses strong magnetic fields to measure the distribution of water molecules in the body. For example, this can be used to visualise various structures in the body, such as blood vessels, and show them as sectional images. In contrast-enhanced breast MRI, the blood circulation in the tissue is measured. The technique is extremely accurate but, in some cases, it is difficult to say whether identified nodes are malignant or whether the tissue is just well supplied with blood due to other e.g. inflammatory reasons.

A second MRI technique, diffusion-weighted imaging (DWI), maps the motion of water molecules in the investigated structures and can also measure it objectively by means of the apparent diffusion coefficient (ADC). The study team has integrated the DWI technique in with their conventional MRI protocol.

Paola Clauser, Department of Biomedical Imaging and Image-guided Therapy of the MedUni Vienna and Vienna General Hospital, member of the Comprehensive Cancer Center (CCC) of the two institutions and lead author of the study, explains: "DWI enables us to characterise lesions much better. Because: hydrogen molecules "dance" faster in healthy tissue than they do in malignant tumours. Carcinomas alter tissue on a microscopic scale and thereby inhibit the motion of water molecules. We have now shown that we do not need to take biopsies from breast tumours, if the threshold value (ADC) is equal to or greater than 1.5+10-3 mm2/s."

Only three more minutes

DWI only takes a maximum of three minutes but improves diagnosis considerably. Pascal Baltzer, Department of Biomedical Imaging and Image-guided Therapy, MedUni Vienna and Vienna General Hospital, member of the CCC and principal investigator explains: "The multicentre study enabled us to establish this threshold value as an objective, standardised biomarker. It can be used anywhere, since it is largely independent of the equipment, the experience of the radiologist, the measuring time and the measuring technique." DWI is now well established in the diagnosis of stroke and is becoming increasingly popular in cancer diagnostics as well. Every radiological facility is therefore able to carry it out. Baltzer explains: "Our finding can be used immediately for diagnostic purposes. It does not require a special centre - every registered radiology department would be able to use it straightaway."

Successful conclusion to a decade of research work

Study leader Balzer has already spent several years investigating whether diffusion is reduced in a tumour, whether this can be measured and, if so, how. This also applies to the ADC threshold value mentioned above. Thomas Helbich, Department of Biomedical Imaging and Image-guided Therapy MedUni Vienna and Vienna General Hospital, CCC board member and research group leader comments: "This finding is the culmination of more than a decade of research work. We established, researched, refined and evaluated the technique in house, and have published countless studies relating to it. However, it was only in this project that we succeeded in clearly validating and establishing the threshold value. Our next goal is to improve the standard we have now established, thereby potentially reducing biopsies even further."

Des Plaines, IL - Initial management with inhaled methoxyflurane in the emergency department did not achieve the prespecified substantial reduction in pain, but was associated with clinically significant lower pain scores compared to standard therapy. That is the conclusion of a study titled Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care that was published recently in the February 2021 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

According to findings of the controlled randomized trial, secondary outcomes included the pain score at multiple time points and the difference in the proportion of patients achieving a >2 point reduction on the pain numerical rating scale. Additionally, methoxyflurane use was not associated with any serious adverse events and was not associated with a significant change in opioid use among emergency department patients.

The lead author of the study is Lisa Brichko, MBBS (Hons), DCH, MHM, of the Emergency and Trauma Centre at Alfred Health in Melbourne, Australia. The findings of the study are discussed with the author in a recent AEM podcast titled The RAMPED Trial - It's a Gas, Gas, Gas.