Body

New research from health psychologists at Staffordshire University explores why some employees feel guilty about taking their legally entitled breaks.

The paper's lead author Dr Mike Oliver explained: "The legally required minimum time for a lunch break at work is 20 minutes, however there is a growing trend nationally for large numbers of people not to take breaks at work, with surveys reporting that between 66% and 82% of workers don't always take their breaks.

"So, how have we got to the point where some people feel guilty about taking their legally allowable break? We were curious to look at the psychological and social behaviours of office workers to understand the enablers and barriers."

With many employees now working from home during the lockdown, Mike believes that some people may find it even harder to take breaks.

"We found that one of the best ways to make sure that you take breaks is to take them with your work colleagues, or to be encouraged to take them by your boss. If they are not physically near you, we may find it harder to act on these social prompts."

For the research, groups of office workers at a large employer of differing levels of seniority were asked about their lunch break habits.

The analysis identified five key themes:

1. People's behaviours depend on various factors - it is not as simple as having those who do take breaks and those who don't.

2. The influence of social and work relationships - if your colleagues take breaks then you are more likely to yourself and vice-versa.

3. Faced with a choice when they're really busy, even if someone wants to take a break, then work "wins".

4. Contradictory feelings - lots of people feel anxious and guilty about taking breaks, although some simply don't.

5. Being 'fair game' for work related matters if you remain at your desk at break times.

Mike, who completed his Professional Doctorate in Health Psychology at Staffordshire University last year, said: "This paper highlights the complex relationships that people have with taking breaks, with others and with their physical environment. Some participants did recognise the importance of taking a break in the middle of the day, but others appeared to convince themselves that by doing a less intense work activity, such as responding to emails, whilst eating their lunch at their desk, would actually be taking a break.

"The greater importance that people appear to be placing on completing their work over the time they give themselves for breaks, or simply the sheer volume and pressure of work, may go some way to explaining this pattern of behaviour."

Mike and colleagues recommend further research and organisational changes to support improved workplace health and wellbeing.

He added: "There is mounting concern about the amount of time people spend sitting down at work and not being physically active, so it is really important that people don't put work ahead of breaks and their own physical and psychological health."

ITHACA, N.Y. - New Cornell-led research shows that inadequate funding is the main barrier to better surveillance and control of ticks, including the blacklegged tick, which spreads Lyme disease, the No. 1 vector-borne illness in the country.

Insufficient infrastructure, limited guidance on best practices and lack of institutional capacity also are impediments to improved tick monitoring, the researchers found.

Their report, "A Survey of Tick Surveillance and Control Practices in the United States," published June 17 in the Journal of Medical Entomology. The lead author is Emily Mader, program manager of the Northeast Regional Center for Excellence in Vector-Borne Diseases (NEVBD) and a member of the lab of Laura Harrington, professor of entomology, NEVBD director and a co-author of the study.

The study identifies what methods public health agencies use to track ticks, the barriers they have and what aid they might need. The study also generated a directory of tick surveillance programs, which did not exist previously.

Aside from Lyme disease, multiple tick species can infect people and animals with a wide variety of other pathogens. Public health and medical professionals have seen a dramatic rise in these tick-borne illness over the last 15 years.

"Vector-borne diseases are only going to become an increasing threat in the world, [including] the United States," Mader said, "and we really don't know how to address that threat unless we study it."

Mader and colleagues surveyed 140 vector-borne disease professionals who work in state, county and local public health and vector control agencies. The survey addressed: tick surveillance programs; pathogen testing methods; tick control practices; how data is communicated; and barriers to developing and operating programs.

Cornell impacting New York State

The results showed that close to half of the respondents were engaged in active tick surveillance, meaning they collect ticks from the environment. Nearly two-thirds engaged in passive surveillance - a kind of crowdsourcing where members of the public send in tick samples.

Active surveillance costs more as it requires trained personnel, transport and storage costs, but it offers more detailed location and ecological information that informs risk compared to passive surveillance. Some programs conducted no tick surveillance.

"If you want to know how the public health threat of ticks is changing from year to year, you need to have the data," Mader said. "We found that [surveillance] programs just weren't able to be sustained across time."

Lack of access to pathogen testing services for many programs was another major barrier to getting better information about the public health threat of ticks in an area.

The survey also found that partnerships between tick surveillance programs within state health or agriculture departments often relied on academic partners. Universities may absorb some costs, provide diagnostic services and provide labor with student interns.

"The most prevalent barrier to developing and sustaining a tick surveillance program across time is just lack of funding," Mader said. County programs often rely on funding from county taxes, while state programs receive state budget appropriations or federal grants.

Many existing programs are in areas where blacklegged ticks live; these communities may have a long history of tick-borne illness.

The survey has already provided important information to bridge knowledge gaps, Mader said. One of the biggest barriers for effective tick surveillance has been lack of standardized guidelines on how to survey the environment for certain tick species, each of which behave uniquely, live in varying habitats, and are collected in different ways.

In response this need, the Centers for Disease Control and Prevention (CDC) recently issued two documents on collecting ticks from the environment.

NEVBD will work to identify more such gaps and provide the knowledge or resources that people need, Mader said.

A new test developed at CHU Sainte-Justine in Montreal will enable better management of patients with severe combined immunodeficiency (SCID). The results of this work was presented Tuesday in the medical journal Blood Advances published by the American Society of Hematology.

Routine neonatal screening, although not yet available in Quebec, has led to an increase in the incidence of patients diagnosed with SCID in North America in recent years. This syndrome, a group of rare hereditary genetic disorders, is characterized by a total absence of immune system function, including an absence of T-lymphocytes, the white blood cells that play a crucial role in the body's immune defence. Without appropriate treatment, the disorder is fatal during the first months of life in the majority of cases.

Many of the genes involved in SCID have been identified, but clinicians sometimes come across patients who do not have any identified genetic abnormalities.

'Don't know the genetic cause'

"It's very frustrating. In about seven per cent of patients, we can't provide optimal care because we don't know the genetic cause," said Dr. Elie Haddad, a pediatric immunologist at CHU Sainte-Justine and expert in the field of SCID.

"Depending on the nature of the mutated gene, there are two treatments for SCID: either a bone marrow transplantation or a thymus transplantation," said Haddad. "We still need to be able to identify the type of disease in order to choose the correct treatment option."

The gene involved can either disrupt hematopoietic stem cells in the bone marrow that consequently cannot naturally become T-cells, or it can affect the function of the thymus. The thymus is an organ in which immature white blood cells from the bone marrow "learn" to become T-cells.

When doctors are unable to identify the real cause of the disorder, they usually turn to bone marrow transplantation. They do so for two reasons: first, transplants are easier to perform, and second, among the known genes, more are responsible for a dysfunction of the hematopoietic cells than for a malfunction of the thymus. However, knowing the origin of the disease is critical, because if it's the thymus that's not working properly, then the bone marrow transplant will have no effect, and vice versa.

"Given this clinical need, our goal was to create a functional test by taking a very small volume of peripheral blood rather than a bone marrow sample, which is a more complex process to perform in babies and more invasive than a simple blood test," said Panojot Bifsha, first author of the study.

In the laboratory, a very small number of stem cells is isolated from patients using a limited amount of blood (3 to 5 mL). A test with a 3D culture that mimics the function of a human thymus is used to test this small number of cells, and a response is obtained in less than five weeks. If the results are normal, thymus transplantation is recommended, but if they are abnormal, then a bone marrow transplant is preferred.

'A relatively quick response'

"Our 3D culture system is unique because it allows us to test a very small number of stem cells circulating in the blood and get a relatively quick response," Haddad said. "We received blood samples from all over North America, which allowed us to validate our method."

A similar study conducted with bone marrow samples at the U.S. National Institutes of Health (NIH) produced similar results, proving the reliability of the test developed at CHU Sainte-Justine from a blood sample. The U.S. study was also published today in Blood Advances.

As Quebec's hub of care and research for children with rare or serious diseases, CHU Sainte-Justine strives to stay one step ahead in research niches for which it is famous, such as the genetics of rare diseases and innovative treatments in precision medicine.

Additional studies will be required to further validate the latest test and allow it to be used on more patients.

University of British Columbia (UBC) researchers have led an international team in developing a new test to better diagnose different types of ovarian cancer, a tool that could one day guide and improve treatment options for women diagnosed with the most common and deadliest form of the disease.

The development and validation of the test are outlined in a new study, published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. The study--led by researchers at UBC's faculty of medicine, University of New South Wales, Huntsman Cancer Institute, Peter MacCallum Cancer Centre and Mayo Clinic--is one of the largest ovarian cancer investigations to date, involving data compiled by more than 50 research institutes and involving more than 3,800 ovarian cancer patients worldwide.

"With this new test, we'll be able to give researchers, clinicians and patients more insight into the disease, which could pave the way for more targeted treatment down the road," says the study's senior author, Dr. Michael Anglesio, a molecular biologist, assistant professor in UBC's department of obstetrics and gynaecology, investigator at the Vancouver Coastal Health Research Institute (VCHRI) and scientist at OVCARE, B.C.'s multidisciplinary gynecological cancer research team.

The new test, known as PrOTYPE (Predictor of high-grade serous Ovarian carcinoma molecular subTYPE), is specifically designed to analyze and classify high-grade serous ovarian cancer, the most common and lethal form of ovarian cancer. Principal investigators validated the test in laboratories at BC Cancer and Vancouver General Hospital.

Using PrOTYPE, researchers and clinicians alike will be able to further classify an individual patient's tumour into one of four known molecular subtypes, each with its distinct biological features believed to respond differently to treatment options.

"Right now, high-grade serous ovarian cancer patients are all treated the same, but by knowing what subtype their tumour falls into, we can begin to explore how certain treatments may prove more beneficial for individual patients," says the study's lead author Dr. Aline Talhouk, a translational data scientist, assistant professor in UBC's department of obstetrics and gynaecology, VCHRI investigator and OVCARE scientist.

Prior to the development of PrOTYPE, subtyping tests using gene expression analysis for high-grade serous ovarian cancer relied on the aggregation of large patient cohorts and the examination of all of the genes in the genome at once -- a situation that made them impractical for use in clinical settings, says Anglesio.

"Doctors will never see a few hundred patients walk through their clinic door at one time. It's just not the reality," says Anglesio.

With PrOTYPE, which was designed for clinical use, a small amount of information--55 informative genes from a small tissue sample--can quickly determine the tumour subtype with more than 95 per cent accuracy. The researchers also developed a corresponding web tool, enabling clinicians to print out a report that can be added to a patient's records.

"We've developed a push-button solution. All that's needed is the tumour from the patient in question and a common reference to compare the data to. Before this test, no one could do that," says Anglesio. "We now have a robust way of figuring out which of the four subtypes a patient fits into."

The researchers see great potential for the test to one day guide patient care. The test is already being used in ongoing clinical trials investigating whether certain subtypes are more sensitive to particular treatments among women with recurrent high-grade serous ovarian cancer.

"This test has opened up new opportunities and treatment avenues to explore. It will be important to re-evaluate treatment options and test new targets for therapeutics in light of this new ability," says Talhouk.

Bose-Einstein condensates are often described as the fifth state of matter: At extremely low temperatures, gas atoms behave like a single particle. The exact properties of these systems are notoriously difficult to study. In the journal Physical Review Letters, physicists from Martin Luther University Halle-Wittenberg (MLU) and Ludwig Maximilian University Munich have proposed a new theory to describe these quantum systems more effectively and comprehensively.

Research into the exotic state of matter dates back to Albert Einstein, who predicted the theoretical existence of Bose-Einstein condensates in 1924. "Many attempts were made to prove their existence experimentally," says Dr Carlos Benavides-Riveros from the Institute of Physics at MLU. Finally, in 1995, researchers in the U.S. succeeded in producing the condensates in experiments. In 2001 they received the Nobel Prize for Physics for their work. Since then, physicists around the world have been working on ways to better define and describe these systems that would enable their behaviour to be more accurately predicted.

This normally requires extremely complex equations and models. "In quantum mechanics, the Schrödinger equation is used to describe systems with many interacting particles. But because the number of degrees of freedom increases exponentially, this equation is not easy to solve. This is the so-called many-body problem and finding a solution to this problem is one of the major challenges of theoretical and computational physics today," explains Benavides-Riveros. The working group at MLU is now proposing a method that is comparatively simple. "One of our key insights is that the particles in the condensate interact only in pairs," says co-author Jakob Wolff from MLU. This enables these systems to be described using much simpler and more established methods, like those used in electronic quantum systems.

"Our theory is in principle exact and can be applied to different physical regimes and scenarios, for example strongly interacting ultracold atoms. And it looks like it will be also a promising way to describe superconducting materials," concludes Jakob Wolff.

Researchers at Orygen have found that some young people with early stage first episode psychosis (FEP) can experience reduced symptoms and improve functioning without antipsychotic medication when they are provided with psychological interventions and comprehensive case management.

The Staged Treatment and Acceptability Guidelines in Early Psychosis (STAGES) study compared two groups of young people, aged 15 - 25 years, presenting with FEP to a specialist early psychosis service.

Both groups received intensive psychosocial intervention, with one group also receiving low dose antipsychotic medication and the other receiving a placebo. The results have been published in Schizophrenia Bulletin Open.

The study found that the addition of antipsychotic medication to intensive psychosocial intervention did not lead to superior outcomes in symptoms and functioning within the first six months, suggesting that antipsychotic medication may not be needed early in the course of illness for all people within the spectrum of psychosis.

Orygen researcher Dr Shona Francey, who led the study, said the team wanted to investigate whether medication was an essential part of treatment for young people with early stage FEP.

"For a significant number of young people, it is. But, I think some young people can recover, at least initially, from their psychosis without medication," she said.

Current practice recommends anti-psychotic medication be taken from the outset of psychotic illness in order to achieve rapid recovery and improvement of psychotic symptoms.

However, Dr Francey said, in reality, a lot of people vote with their feet and don't take their medication for a variety of reasons.

"Medications can have heavy-duty side effects for young people, including weight gain which is a significant issue that young people are concerned about. There are also various sexual and other physical side effects that young people on medication have to contend with."

Dr Francey said that not all young people could delay their antipsychotic medication. "For many young people with early stage FEP, medication is an essential part of their treatment plan. But, for those young people who do not want medication, psychological interventions and comprehensive case management could be a feasible model of treatment.

"What the findings of this research tell us is that if a young person is reluctant to take medication for FEP, a period of intensive psychosocial treatments could be offered as an alternative," Dr Francey said.

She said a larger trial would be required to investigate whether antipsychotic-free treatment could be recommended for particular groups of young people with FEP.

"Young people currently using medication as part of their supervised treatment should continue to do so under the direction of their doctor," Dr Francey said.

Structural biology has been used to 'map' part of a protein called SMCHD1, explaining how some changes in SMCHD1 cause certain developmental and degenerative conditions.

Publishing in the journal Science Signaling, the Walter and Eliza Hall Institute team revealed the structure of the portion of the SMCHD1 protein that is crucial to its function in 'switching off' genes. Inherited mutations in this part of SMCHD1 have been linked to a developmental disorder and a form of muscular dystrophy.

The decade-long research project was led by Dr Kelan Chen, Ms Alexandra Gurzau, Dr Richard Birkinshaw, Associate Professor James Murphy, Professor Marnie Blewitt and Associate Professor Peter Czabotar.

At a glance

- Advanced structural biology techniques have been used to reveal a new map of a portion of the protein SMCHD1.

- The new structure provides more detail about how SMCHD1 functions to alter gene expression.

- The research team have used the structure to better understand how inherited changes in SMCHD1 alter its function and cause certain developmental and degenerative diseases.

Regulating gene expression

The human genome contains around 20,000 genes, which direct the production of proteins within cells, impacting how cells function. Genes can be 'switched on' or 'switched off' at different times and in different cell types, altering the amounts of the corresponding protein within cells and changing the cells' behaviour. The right balance of this gene 'expression' is critical for healthy development and throughout life.

SMCHD1 is a protein that can specifically switch genes off, impacting how cells function. Inherited changes in SMCHD1 have been linked to a form of muscular dystrophy, called facioscapulohumeral dystrophy (FSHD), as well as a rare developmental disorder, called Bosma arhinia micropthalmia syndrome (BAMS), said PhD student Ms Alexandra Gurzau.

"By investigating the structure and biology of SMCHD1, we hope to better understand the diseases that are associated with changes in SMCHD1, as well as revealing how this protein functions in healthy cells," she said.

"Some of the changes in SMCHD1 that cause disease occur in one part of SMCHD1 - called its 'hinge domain' - that binds to DNA and also enables SMCHD1 proteins to clump in pairs, called dimers. This part of the protein was very poorly understood, so we focused our attention onto it and investigated its structure," Ms Gurzau said.

A challenging protein

Dr Richard Birkinshaw said that SMCHD1 was a particularly challenging protein to elucidate a structure for. "This protein was about five times bigger than a typical human protein, and its hinge domain had a number of features that made it hard to purify and crystalise, two essential steps before we could determine its structure," he said.

"It was a long process, started by Dr Kelan Chen and involving the CSIRO C3 Collaborative Crystallization Centre, but we eventually were able to apply advanced technologies at the Australian Synchrotron called 'single anomalous dispersion' and 'small-angle X-ray scattering' to solve the structure of the SMCHD1 hinge domain. This created a three-dimensional 'map' of this part of the protein, showing its shape and the spatial connections between its different parts," Dr Birkinshaw said.

Ms Gurzau said the structure revealed how SMCHD1 binds to DNA, and which parts of the protein enabled it to bind with its pair.

"We could also deduce from the structure why some disease-associated changes in the hinge domain prevent SMCHD1 from functioning. By recreating these different forms of the protein within cells, we were able to use imaging to visualise how these variants behaved differently from the unchanged version of SMCHD1 - an important advance in understanding the associated diseases," she said.

Dr Birkinshaw said SMCHD1's structure also upended algorithms that had been developed to predict the structure of unknown proteins.

"The structures of many 'SMC' proteins related to SMCHD1 had already been solved, but our work revealed the structure of the SMCHD1 hinge domain is quite different from equivalent regions in these proteins.

"Our data is now being used as a challenge for structure prediction algorithms, as the structure we discovered is quite different from what we had expected. This challenge tests which of these algorithms can most accurately predict our structure and helps to improve the algorithms to produce more accurate models," Dr Birkinshaw said.

Associate Professor James Murphy said the latest discoveries supplemented the team's research into developing drugs that alter the function of SMCHD1, as a potential new therapy for some diseases associated with the protein.

"By understanding in more detail how SMCHD1 functions, we can better understand its role in health and disease. Another group had already solved the structure of a separate part of the protein, so we've added more detail to the entire protein's structure - although half of the protein is still 'uncharted'," he said.

DETROIT -A Henry Ford Hospital study published in the Journal of Arthroscopic and Related Surgery, has found that patients who underwent knee surgery and other types of sports medicine procedures could manage their pain without opioids or a minimal dosage.

"This is a large prospective study and our hope is that non-opioid use will gain momentum and that others may tweak our protocol and use it throughout orthopedics, from joint surgery to spine surgery and other surgeries" says Vasilios (Bill) Moutzouros, M.D., chief of Sports Medicine, a division of the Department of Orthopedic Surgery and the study's lead author, "We hope that we are helping to change practices not just in sports medicine surgery but in all surgery."

The purpose of the prospective study was to determine whether postsurgical pain following common sports medicine procedures could be managed effectively with a nonopioid multimodal analgesic protocol that relies more on non-steroid and anti-inflammatory medicine. It included 141 patients who underwent surgery between May and December 2018 for ACL reconstruction, shoulder and rotator cuff repairs or a torn knee meniscus. The study is the first in a series by Henry Ford researchers examining the issue.

Researchers found that 45 percent of patients had low levels of pain that was effectively managed by the regimen. Drowsiness was the only side effect reported by patients. All 141 patients were satisfied with how their post-surgery pain was managed by their doctor.

Even though patients were prescribed oxycodone as part of their regimen, none used it for pain control. Researchers say the regimen appeared to be essentially multiplicative, alleviating the need for patients to take the oxycodone.

Patients who required opioids were more likely to have a history of anxiety/depression and reported higher pain scores than those who didn't need to take them.

"This kind of research has the potential to decrease opioid use in the general population as we find that many patients who abuse opioids started using them after a surgery and got hooked on them. It starts with the more common surgeries. By eliminating surgical opioid use, we are contributing to the reduction in opioids, which helps decrease dependence," says Kelechi Okoroha, M.D., a Henry Ford sports medicine physician and a study co-author.

Dr. Toufic Jildeh, a study co-author and administrative chief resident in orthopedics at Henry Ford, says sports medicine physicians can "play a direct role in improving pain management and decreasing opioid prescribing."

"There are currently no protocols that completely eliminate opioid use," he says. "This study strongly suggests that eliminating opioids postoperatively is actually possible."

Prior Henry Ford studies that focused on perioperative pain control and minimizing post-operative pain and opioid consumption after sports surgery led researchers to better understand risk factors that contribute to postoperative pain.

"It's a practice changing study," Dr. Moutzouros says. "This type of research allows physicians to look at how we manage pain differently in the post-surgical environment. It allows us to change our practices and become safer. What we're trying to do is support each individual patient and reassure them that we are going to prescribe little if any opioids for their pain control to mitigate or eliminate a potential for addiction."

A sequencing pipeline that integrates a patient's specific tumor genetic data boosts the sensitivity of tests that detect cancer cell DNA circulating in the blood, according to a newly published study. The platform could routinely detect hard-to-spot circulating tumor DNA (ctDNA) on the order of one mutant molecule per 100,000 in plasma samples from 105 patients with various cancers. Although further work is needed, the test represents a stride in creating a ctDNA assay sensitive enough to be used in the clinic to monitor cancers. Most current tests for cancer patients are overly invasive or can fail to accurately track changes in tumors. Tests that seek out residual ctDNA in blood samples would be less invasive and would allow clinicians to better monitor tumors during treatment, potentially spotting relapses earlier. However, ctDNA can be hard to detect because it is sometimes present in only tiny amounts in blood, especially in people with small tumors or residual disease. Jonathan Wan and colleagues solved this issue with their Integration of VAriant Reads (INVAR) pipeline, a technique that analyzes hundreds of patient-specific mutations to better detect ctDNA. When tested with 176 plasma samples from 105 patients with melanoma, lung cancer, kidney cancer, or other types of tumors, INVAR quantified ctDNA to a degree of one mutant molecule per 100,000, and in one patient could detect ctDNA on the order of 2.5 parts per million. The technique also detected ctDNA in eight of 20 patients with melanoma that recurred after surgical removal. Wan et al. caution that INVAR will have to be applied with larger datasets to optimize its ability to detect residual ctDNA in patients with a high risk of cancer recurrence.

Combining more healthy lifestyle behaviors was associated with substantially lower risk for Alzheimer's disease in a study that included data from nearly 3,000 research participants. Those who adhered to four or all of the five specified healthy behaviors were found to have a 60% lower risk of Alzheimer's. The behaviors were physical activity, not smoking, light-to-moderate alcohol consumption, a high-quality diet, and cognitive activities. Funded by the National Institute on Aging (NIA), part of the National Institutes of Health, this research was published in the June 17, 2020, online issue of Neurology, the medical journal of the American Academy of Neurology.

"This observational study provides more evidence on how a combination of modifiable behaviors may mitigate Alzheimer's disease risk," said NIA Director Richard J. Hodes, M.D. "The findings strengthen the association between healthy behaviors and lower risk, and add to the basis for controlled clinical trials to directly test the ability of interventions to slow or prevent development of Alzheimer's disease."

The research team reviewed data from two NIA-funded longitudinal study populations: Chicago Health and Aging Project (CHAP) and the Memory and Aging Project (MAP). They selected participants from those studies who had data available on their diet, lifestyle factors, genetics, and clinical assessments for Alzheimer's disease. The resulting data pool included 1,845 participants from CHAP and 920 from MAP.

The researchers scored each participant based on five healthy lifestyle factors, all of which have important health benefits:

At least 150 minutes per week of moderate- to vigorous-intensity physical activity - Physical activity is an important part of healthy aging.

Not smoking - Established research has confirmed that even in people 60 or older who have been smoking for decades, quitting will improve health.

Light-to-moderate alcohol consumption - Limiting use of alcohol may help cognitive health.

A high-quality, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet - The MIND diet focuses on plant-based foods linked to dementia prevention.

Engagement in late-life cognitive activities - Being intellectually engaged by keeping the mind active may benefit the brain.

The research team then compared the scores with outcomes of clinical diagnosis of Alzheimer's in the CHAP and MAP participants. Lead author of the paper, Klodian Dhana, M.D., Ph.D., assistant professor at Rush University Medical Center, emphasized that the combination of healthy lifestyle factors is key. He wrote that compared to participants with no or one healthy lifestyle factors, the risk of Alzheimer's was 37% lower in those with two to three, and 60% lower in those with four to five healthy lifestyle factors.

"This population-based study helps paint the picture of how multiple factors are likely playing parts in Alzheimer's disease risk," said Dallas Anderson, Ph.D., program director in the Division of Neuroscience at NIA. "It's not a clear cause and effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction."

A 2017 research review and report commissioned by NIA concluded that evidence on lifestyle factors such as increasing physical activity, along with blood pressure management and cognitive training, is "encouraging although inconclusive" for preventing Alzheimer's. Since then, more research has emerged, such as the SPRINT MIND trial, which suggests intensive blood pressure control may slow age-related brain damage, and new trials have launched. For example:

The NIA-funded MIND Diet Intervention to Prevent Alzheimer's Disease is an interventional clinical trial comparing parallel groups with two different diets. An NIA-funded collaboration between Rush University and Harvard T.H. Chan School of Public Health and Brigham & Women's Hospital (grant number R01AG052583). MIND has enrolled more than 600 participants and is ongoing with an anticipated completion date in 2021.

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a multisite randomized clinical trial designed to evaluate whether lifestyle interventions -- including the MIND diet -- may protect cognitive function in older adults who are at increased risk for cognitive decline. NIA is funding the imaging, neurovascular, and sleep ancillary studies of POINTER.

NIA is currently funding more than 230 active clinical trials on Alzheimer's and related dementias. Of those, more than 100 are nondrug interventionsl, such as exercise, diet, cognitive training, sleep, or combination therapies. People interested in participating in clinical trials can find more information on the NIA website.

Slightly less than half (48%) of New Yorkers know how vaccines actually work, but those who do are about 7% more likely to say they will take a COVID-19 vaccine when one becomes available. Knowledge apart, however, 81% of those New Yorkers who have seen the symptoms of COVID-19 in their own households say they are likely to accept a vaccine.

These are key findings from responses to questions about coronavirus infection and vaccines that could prevent it that were asked in the tenth city and statewide tracking survey from the CUNY Graduate School Health Policy (CUNY SPH), conducted May 29-31.

"A public health survey is not supposed to be a classroom test," said Dr Ayman El-Mohandes, Dean of CUNY SPH. "Survey researchers usually ask only what people have experienced and what they think. We added a vaccine knowledge question to our latest survey because we believe that if people understand what vaccines are, how they work and what they do, they may be more likely to accept them,"

Respondents were asked, "Of the following statements, which describes most accurately how vaccines work?" Four options were given, including a standard definition of how a vaccine works, which states that, "Vaccines prepare your immune system to recognize and disarm harmful viruses and bacteria."

When asked whether or not they plan to take a coronavirus vaccine, a substantial number of New Yorkers (74%) said they do. Accurate knowledge of how vaccines work seems to increase the likelihood of accepting a vaccine: those who chose the correct statement describing how vaccines work were about 7% more likely to accept the vaccine when it becomes available.

"These numbers are encouraging. But when a 70% immunization rate is the absolute minimum that public health experts believe will be required to protect a community against the coronavirus, even a small gap in public understanding is troubling. Nor would one wish direct experience of this terrible disease to be the best teacher of the need for a vaccine", Dr. El-Mohandes explained.

Who Knows How Vaccines Work and Who Doesn't?

Some subgroups were more likely to know how a vaccine works than others.

The correlation between a respondent's age and a correct answer was striking. More than 3 in 5 (62%) of New Yorkers aged 18-29 chose the right definition. The percentage of correct answers dropped under half among older respondents. Among people aged 30-44, 47% answered correctly; 45-59, 43% answered correctly, a figure that dropped to 41% among respondents aged 60 or older.

Women (51%) were more likely to know how vaccines worked than men (45%).

Education correlated predictably with knowing how a vaccine works. While almost 5 in 8 (61%) of respondents with an undergraduate or postgraduate degree answered correctly, the percentages dropped to 50% among those reporting some college and 34% for those with a high school degree or less.

Race and ethnicity were also factors. Nearly three in five (56%) of respondents identifying themselves as White knew how a vaccine worked, compared to 49% of Asians, 42% of African-Americans and 42% of LatinX/Hispanic respondents.

"This is important information, as it will help public health communicators begin to frame precisely-worded educational messages and choose audience-specific communication media to improve the climate of acceptance for a future COVID-19 vaccine," explained Dr. Scott Ratzan, Distinguished Lecturer at CUNY SPH.

Do vaccine opponents or conspiracy theorists present an obstacle?

All survey respondents were asked to what degree they opposed or accepted the idea of vaccination generally. Here the distribution clearly favored vaccine acceptance: Only 3% of respondents said they were totally opposed to vaccinations, while 16% identified themselves as hesitant to vaccinate. About a quarter (26%) of respondents said they would decide based on credible information and a similar number said they would follow their doctor's advice. More than three respondents in ten (31%) described themselves as vaccine believers.

In general, however, New Yorkers from all audience segments have grown extremely suspicious of the entire environment surrounding COVID-19. Almost two-thirds (65%) believe that "the spread of the COVID-19 pandemic or the response to it are influenced by the private influence of powerful but hidden groups" is definitely or probably true. Notably, of those who got the vaccine question right, 57% believe this, and 43% do not. That is not terrific, but it is quite a bit better than among those who got the vaccine definition question wrong: 72% believe in the conspiracy and 28% do not.

"These findings suggest that public health leaders face unusual added challenges in persuading the public to continue to modify their daily lives as well as to accept a coronavirus vaccine, when one becomes available," Dr. Ratzan stated.

Can potential vaccine refusers' minds be changed?

The 27% of all survey respondents who said they would not be likely to take a new coronavirus vaccine were asked which factors might induce them to change their minds about immunizations.

Expense does not appear to be a major factor. About four in ten (39%) say cost would be a factor in their refusal. A similar proportion (36%) said they would consider the vaccine if it were given free.

Completely convincing evidence of a coronavirus vaccine's safety (77%) and efficacy (75%) could change these respondents' minds, however.

Credibility of the source of this evidence could prove elusive, however. Just 42% of these likely vaccine refusers would be swayed by approval of a coronavirus vaccine from the FDA or CDC.

"This last finding genuinely startled me," said Dr. Kenneth Rabin, Senior Scholar at CUNY SPH. "I have spent the last 40 years in health communication and for that entire time the FDA and CDC have been almost universally regarded by doctors, consumers and the news media as the gold standards of information about the safety and efficacy of vaccines, and of people's need for them."

The complete survey results and related commentary can be found at https://sph.cuny.edu/research/covid-19-tracking-survey/week-12-part-2-vaccines/ and JHC Impact, an initiative of the Journal of Health Communication: International Perspectives.

Survey methodology:

The CUNY Graduate School of Public Health and Health Policy (CUNY SPH) survey was conducted by Emerson College Polling from May 29-31 (week 12). This tracking effort started March 13-15 (week 1), and continued with questions fielded March 20-22 (week 2) and March 27-29 (week 3), April 3-5, 2020 (week 4), April 10-12, 2020 (week 5), April 17-29 (week 6), April 24-26, 2020 (week 7), May 1-3, 2020 (week 8), and May 15-17, 2020 (week 10).

The sample for the NY Statewide and New York City results were both, n=1,000, with a Credibility Interval (CI) similar to a poll's margin of error (MOE) of +/- 3 percentage points. The data sets were weighted by gender, age, ethnicity, education and region based on the 2018 1-year American Community Survey model. It is important to remember that subsets based on gender, age, ethnicity and region carry with them higher margins of error, as the sample size is reduced. In the New York City results, data was collected using an Interactive Voice Response (IVR) system of landlines (n=475), SMS-to-online (n=327) and an online panel provided by MTurk and Survey Monkey (n=197). In the Statewide results, data was collected using an Interactive Voice Response (IVR) system of landlines (n=469), SMS-to-online (n=319) and an online panel provided by MTurk and Survey Monkey (n=212).

The CUNY Graduate School of Public Health and Health Policy (CUNY SPH) is committed to teaching, research, and service that creates a healthier New York City and helps promote equitable, efficient, and evidence-based solutions to pressing health problems facing cities around the world.

East Hanover, NJ. June 17, 2020. Researchers at Kessler Foundation conducted a comprehensive review of pharmacologic agents used in the treatment of multiple sclerosis, seeking evidence for efficacy for the cognitive dysfunction experienced by more than half of affected individuals. The article, "Cognitive efficacy of pharmacologic treatments in multiple sclerosis: A systematic review," was published open access in CNS Drugs 2020 May 02. (doi: 10.1007/s40263-020-00734-4) The authors are Michelle H. Chen, PhD, Helen Genova, PhD, and John DeLuca, PhD, of Kessler Foundation. Yael Goverover, PhD, of New York University, is a visiting scientist at Kessler Foundation.

Researchers identified 87 articles, using the PubMed and PsycINFO databases and the 2017 American Academy of Neurology (AAN) criteria for therapeutic trials. Standardized effect sizes were calculated for comparison across trials.

Agents from the following therapeutic categories were represented: Disease-modifying therapies (DMTs) (interferon B-1a, B1b, glatiramer acetate, natalizumab, fingolimod); Symptomatic therapies (dalfampridine; cognition enhancers: rivastigmine, Gingko biloba, donepezil; Stimulants: modafinil, armodafinil, methylphenidate, amphetamine sulfate, amantadine); and 'Other' therapies that were neither DMTs nor stimulants (eg, estrogen, methylprednisolone, simvastatin, human erythropoietin).

Review of the studies of DMTs failed to support effectiveness for treating cognitive deficits, with a majority of class III and IV evidence. "We found no class I evidence, and class II evidence was minimal to none," said Dr. Chen, postdoctoral fellow in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation.

Although most of the studies of symptomatic therapies were randomized controlled trials with primary cognitive outcomes (i.e., higher quality evidence), there were contradictory findings, resulting in inconclusive evidence for the cognitive efficacy of symptomatic therapies. For studies involving 'other' agents, there was again insufficient evidence to support their use to treat cognitive problems.

In summary, there was insufficient evidence for cognitive efficacy across the spectrum of pharmacologic agents used in the treatment of multiple sclerosis. "Given the impact of cognitive dysfunction on individuals with MS, it is prudent to explore the potential for cognitive efficacy of available pharmaceuticals," explained Dr. Genova, director of the Center for Neuropsychology and Neuroscience Research. The design of future studies, especially of DMTs, must focus on cognitive outcomes and follow standardized criteria such as the AAN's," she said in conclusion. "Randomized, controlled studies with cognition as the primary outcomes will provide clinicians with the information they need to choose optimal treatments for patients."

A research group from Kumamoto University, Japan, has clarified the mechanism by which human T-cell leukemia virus type 1 (HTLV-1) causes inflammation and oncogenesis. The action of the viral gene HTLV-1 bZIP factor (HBZ) changes the reactivity of immune cells (T cells) infected with HTLV-1 to cytokines, which results in inflammation. This research is expected to contribute to the understanding of the mechanisms of HTLV-1-induced malignant tumors (ATL) and HTLV-1-related inflammatory diseases, and lead to the development of new treatment and prevention strategies.

HTLV-1 is a virus that causes a malignancy of lymphocytes called adult T-cell leukemia (ATL) and a chronic neurological disease called HTLV-1 associated myelopathy (HAM). The virus causes these diseases by increasing the number of infected lymphocytes in the body. Most HTLV-1 infected individuals remain asymptomatic, but in about 2-5% of infected people, infected cells become malignant and develop ATL.

Researchers genetically engineered HBZ transgenic mice (HBZ-Tg) to analyze the function of HBZ; this murine model expresses HBZ in CD4+ T lymphocytes. In their model, CD4+CD25+Foxp3+ T cells increased (these cells also increase in HTLV-1-infected individuals), and the mice developed inflammation and malignant lymphoma. The researchers thus hypothesized that HBZ plays an important role in the pathogenicity of HTLV-1.

In a previous study, the researchers found that HBZ-Tg mice had both inflammation and T-cell lymphoma. The mice with severe dermatitis tended to develop lymphoma. Since an inflammatory cytokine, IL-6, is known to promote carcinogenesis through inflammation in several types of cancers, the researchers thought that IL-6 could also promote oncogenesis in HBZ-Tg and ATL.

To evaluate the roles of IL-6 in the pathogenesis of HBZ, researchers created HBZ-Tg mice that were unable produce IL-6 (HBZ-Tg/IL-6 knockout mice). Unexpectedly, the incidence of inflammation and lymphoma in HBZ-Tg/IL-6 knockout mice significantly increased compared with HBZ-Tg mice, revealing that IL-6 has suppressive effects on the pathogenicity of HBZ. IL-6 is a cytokine with various functions and is known to inhibit the differentiation of regulatory T cells (Treg) that have a suppressive function on immune reaction. Researchers previously reported that Treg-like cells increased with HBZ-Tg and were involved in the development of inflammation in HBZ-Tg mice. This indicates that, in HBZ-Tg mice, IL-6 deficiency further promotes Treg differentiation and accelerates the development of diseases.

On the other hand, HBZ-Tg mice were found to produce the immunosuppressive cytokine, IL-10. In addition, IL-10 promoted the proliferation of T cells derived from HBZ-Tg mice. Since normal mouse T cells were not affected by IL-10 stimulation, HBZ is thought to modulate IL-10 stimulation and promotes cell proliferation. Moreover, HBZ was found to interact with the cellular transcription factors STAT1 and STAT3--which work downstream of the IL-10 signal--and disrupt their transcriptional activities. This suggested a previously unknown mechanism of HBZ-mediated pathogenesis by perturbing the reactivity of CD4-positive T cells to IL-6 and IL-10.

"Our analysis brings us closer to finding the mechanisms which HTLV-1 uses to promote growth of infected cells and sustain persistent infection. We expect that our work will contribute toward the elucidation of the molecular mechanisms of HTLV-1 associated diseases," said Associate Professor Jun-ichirou Yasunaga, who lead the study. "IL-6 and IL-6 receptors are therapeutic targets for autoimmune diseases such as rheumatoid arthritis, and inhibitors for them are currently in clinical use. Our results alert us to the possibility that the blockade of IL-6/IL-6R signaling increases the risk of disease progression in some HTLV-1-infected individuals. Careful evaluations of the risk and efficacy of such a treatment are necessary."

This research was posted online in the Proceedings of the National Academy of Science on 26 May 2020.

[Source]
Higuchi, Y., Yasunaga, JI., Mitagami, Y., Tsukamoto, H., Nakashima, K., Ohshima, K., & Matsuoka, M. (2020). HTLV-1 induces T cell malignancy and inflammation by viral antisense factor-mediated modulation of the cytokine signaling. Proceedings of the National Academy of Sciences, 201922884. doi:10.1073/pnas.1922884117

People who inject illicit drugs can develop potentially deadly infections of the heart, blood, joints and soft tissues. Typically, such infections require weeks of hospitalization to treat effectively. But a new study by researchers at Washington University School of Medicine in St. Louis shows that drug users who, while in the hospital, started IV antibiotics for serious infections and then finished their courses of treatment at home with antibiotic pills fared just as well as those who stayed in the hospital.

The findings, which are available online in Clinical Infectious Diseases, have led Washington University physicians at Barnes-Jewish Hospital to change the treatment recommendations for such patients, who traditionally have been required to stay in the hospital for two to six weeks of IV antibiotic treatment. Now, doctors offer patients who wish to finish treatment at home a prescription for oral antibiotics.

"Most people don't want to stay in the hospital for weeks at a time to get IV antibiotics when they could be treated at home," said lead author Laura Marks, MD, PhD, a clinical fellow in infectious diseases. "But until recently, infectious disease doctors had limited evidence on effective treatment options for patients who could not complete long courses of IV antibiotics. No one wants to offer an ineffective treatment for what could be a life-threatening infection, and so we required everyone to stay. Now we recognize that when someone does not want to stay in the hospital, we can work with the patient to find another way to provide antibiotics."

While the COVID-19 pandemic dominates the news these days, the opioid epidemic continues unabated. An estimated 3 million people in the U.S. have opioid-use disorder. Since the drugs often are injected under unhygienic conditions, the opioid epidemic has brought with it an epidemic of invasive infections. Over the past decade, increasing numbers of people have shown up in emergency rooms with serious bacterial infections related to their IV drug use.

Such potentially lethal infections require long courses of powerful antibiotics. But extended hospital stays can be burdensome, and some people leave the hospital against medical advice before they've received all of the medication prescribed for them. In the past few years, studies have shown that people who have invasive infections for reasons unrelated to use of injectable drugs can be treated successfully with a few days of IV antibiotics in the hospital, followed by oral antibiotics at home. But some doctors have been reluctant to apply the same protocol to people who inject illicit drugs.

"There was this idea that people who inject drugs do not care about their health and would not adhere to an oral antibiotic regimen on discharge. So letting patients leave the hospital partway through an IV antibiotic course was akin to abandoning all treatments," said senior author Michael Durkin, MD, an assistant professor of medicine and a co-director of antimicrobial stewardship at Barnes-Jewish Hospital. "We didn't believe that was true."

Marks, Durkin and colleagues analyzed the medical records of 293 people who had injected illegal drugs and were treated for invasive infections at Barnes-Jewish Hospital at some point from January 2016 through July 2019. The patients were divided into three groups: those who had completed full courses of IV antibiotics in the hospital; those who had begun IV antibiotics in the hospital and then were discharged with prescriptions for oral antibiotics; and those who had started IV antibiotics in the hospital and left without prescriptions. The researchers looked at how many patients were readmitted to the hospital for any reason within 90 days of discharge.

Those who left the hospital without antibiotic prescriptions were more than twice as likely to be readmitted within three months than those who left early with prescriptions, or those who completed treatment in the hospital. The authors calculated that for every three people treated with oral antibiotics, one less person needed to be readmitted to the hospital. Moreover, there was no significant difference between those who stayed in the hospital for full courses of IV antibiotics and those who completed partial courses of IV antibiotics followed by oral antibiotics.

While IV antibiotics are still considered the standard of care for invasive infections, the study's findings suggest that people who do not want to stay in the hospital for weeks should be given the option of taking oral antibiotics at home, even if they most likely became infected by injecting drugs.

"It doesn't matter why patients have an infection," Marks said. "We want to make sure that we provide antibiotics to patients in a setting they prefer. If they are not comfortable staying in the hospital throughout their treatment, we will work to get them back home as soon as it is safe, and they can finish their treatment on an oral alternative."

Marks and Durkin are part of an effort at Barnes-Jewish Hospital and other BJC hospitals to improve care for people with infections linked to injection drug use by providing treatment for substance use disorder alongside antibiotics. The effort is funded by the Centers for Disease Control and Prevention. As part of this study, the researchers compared readmission rates between people who met with the addiction medicine team in addition to an infectious disease specialist, and those who were only treated for their infection. Those who received support for their substance use disorder were 40% less likely to be readmitted within three months.

"If someone comes in with an injection-related infection, they are seen by our infectious disease doctors as well as an addiction medicine physician, a dedicated case manager, and health coaches," Marks said. "We help them make an appointment for substance use disorder treatment location after discharge, and our wraparound team ensures that they get there. They get a follow-up appointment in an infectious disease clinic, too. We try to look at patients as whole people, and provide the best care possible for them."

New research led by Monterey Bay Aquarium is helping to unlock the natural history of one of the most studied places on the planet. By tapping into a collection of dried, pressed seaweed - that dates back more than 140 years - researchers with the Aquarium's Ocean Memory Lab can now offer a window back in time to understand what the bay was like before the impacts of modern human activity.

Read the paper, "Herbaria macroalgae as a proxy for historical upwelling trends in Central California," at the journal Proceedings of the Royal Society B.

Deep marine canyons, a myriad migratory species and an abundant source of nutrients supplied by natural upwelling have attracted the massive concentration of marine science currently focused on Monterey Bay. Despite this proliferation of study and observation here, scientists had always been limited in their attempts to establish baselines of ecosystem health by the extent of available data, which in Monterey Bay extends back to 1946 when the patterns of its natural upwelling started being recorded.

"This part of California's Central coast is renowned for the sheer amount of marine life it can sustain. Even through the pressures of the past century, Monterey Bay is still teeming with birds, whales, fishes and seaweeds," said Monterey Bay Aquarium Chief Scientist Kyle Van Houtan. "These plants and animals were around long before scientists, so we thought if we could find historical samples we might learn something by extracting the information stored in their tissues."

Using that approach, the Ocean Memory Lab generates new information about the ocean's past by combing through scientific collections, museums, and other historical archives. These repositories contain specimens of marine life that have data on ocean conditions locked within their fronds, feathers, shells and other tissues. Aquarium scientists use a variety of chemical analyses to unlock the data held within sample tissues to provide more accurate baselines, and help inform decisions intended to maintain or restore ocean health.

"We were able to add nearly seven decades of data, extracted from seaweed samples more than a century old, to better understand historical changes in Monterey Bay," said Emily Miller, the lead author of the study for the Aquarium and now a researcher at partner institution, the Monterey Bay Aquarium Research Institute. "This information offers us a new perspective on one of the features that makes Monterey Bay home to such diversity, its upwelling cycles. Documenting these patterns helps us to understand shifts in the foundation of the food web, and to make more informed conservation decisions in the future."

Working with colleagues from Stanford University's Hopkins Marine Station and the University of Hawaii, Aquarium researchers based the study on data from the chemical analysis of pressed seaweed samples sourced from herbarium collections from several institutions, dating back to 1878, as well as freshly collected specimens. The samples analyzed came from six species of seaweed, also called macroalgae, that included giant kelp, rockweed, sea lettuce, and grape tongue.

"Izzy Abbott, who was professor of biology at Hopkins, helped to curate and build our collection of algae for over 25 years," said Stephen Palumbi, a professor of marine biology at Stanford University's Hopkins Marine Station. "She and the algae biologists that came before her knew that preserving specimens was vital. But it took this new approach from Monterey Bay Aquarium to dig into the very atoms of the algae and ask the kelp forest questions about the history of the oceans."

Researchers calibrated the accuracy of their chemical analysis by comparing nitrogen stable isotopes from a red algae, Gelidium, with the Bakun upwelling index, a record of the natural Monterey Bay phenomenon going back to 1946. They found a high correlation between the index and data derived from the algae samples from 1946-2018, which demonstrated the nitrogen isotopes in the algae could be used to determine the upwelling pattern. Researchers then used older algae specimens to extend the Bakun upwelling index back to 1878, 70 years before it began being monitored.

One of the research's novel findings, drawn from the additional seven decades of information offered within the seaweed samples, shed more light into ocean conditions in Monterey Bay during the sardine fishery's famous boom and bust in the 1940s and 1950s. Researchers documented poor upwelling conditions in Monterey Bay in the years immediately prior to the crash. This discovery adds a new dimension to an understanding of what role ecosystem changes may have played in the shift from a sardine-dominated system to one that is anchovy-dominated. It could also further inform how fishery management practices are implemented to respond to environmental conditions, something known as ecosystem-based management.

More information on this research and the Ocean Memory Lab is available at the Aquarium's website.