Culture

Engineered capsids for efficient gene delivery to the eye

image: Journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, August 13, 2020--A rational design approach created novel variants of adeno-associated viral (AAV) capsids. These have improved transduction properties in the mouse retina and cornea. as reported in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through September 13, 2020.

The efficient gene delivery of these variants was confirmed in non-human primate tissue.

"The capsid modified AAV2 and AAV5 variants described here have novel attributes that will add to the efficacy and specificity of their potential use in gene therapy for a range of human ocular diseases," said Catherine O'Riordan and coauthors from Sanofi.

"The structural domains of the AAV capsid have become fundamental building blocks of many gene therapy vectors. The work by Dr. O'Riordan and her colleagues takes advantage of the new age of structural biology to intelligently redesign these building blocks rather than relying on empiric screening of variants. This rational design approach holds great promise for the field," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

To understand the machinery of life, this scientist breaks it on purpose

image: Betül Kaçar studies the origins of life, which is why she is at home in several disciplines. She is an assistant professor at the University of Arizona with appointments in the Departments of Molecular and Cellular Biology, Astronomy and the Lunar and Planetary Laboratory.

Image: 
Carl Philabaum

"I'm fascinated with life, and that's why I want to break it."

This is how Betül Kaçar, an assistant professor at the University of Arizona with appointments in the Department of Molecular and Cellular Biology, Department of Astronomy and the Lunar and Planetary Laboratory, describes her research. What may sound callous is a legitimate scientific approach in astrobiology. Known as ancestral sequencing, the idea is to "resurrect" genetic sequences from the dawn of life, put them to work in the cellular pathways of modern microbes - think Jurassic Park but with extinct genes in place of dinosaurs, and study how the organism copes.

In a recent paper published in the Proceedings of the National Academy of Sciences, Kaçar's research team reports an unexpected discovery: Evolution, it seems, is not very good at multitasking.

Kaçar uses ancestral sequencing to find out what makes life tick and how organisms are shaped by evolutionary selection pressure. The insights gained may, in turn, offer clues as to what it takes for organic precursor molecules to give rise to life - be it on Earth or faraway worlds. In her lab, Kaçar specializes in designing molecules that act like tiny invisible wrenches, wreaking havoc with the delicate cellular machinery that allows organisms to eat, move and multiply - in short, to live.

Kaçar has focused her attention on the translation machinery, a labyrinthine molecular clockwork that translates the information encoded in the bacteria's DNA into proteins. All organisms - from microbes to algae to trees to humans - possess this piece of machinery in their cells.

"We approximate everything about the past based on what we have today," Kaçar said. "All life needs a coding system - something that takes information and turns it into molecules that can perform tasks - and the translational machinery does just that. It creates life's alphabet. That's why we think of it as a fossil that has remained largely unchanged, at least at its core. If we ever find life elsewhere, you bet that the first thing we'll look at is its information processing systems, and the translational machinery is just that."

So critical is the translational machinery to life on Earth that even over the course of more than 3.5 billion years of evolution, its parts have undergone little substantial change. Scientists have referred to it as "an evolutionary accident frozen in time."

"I guess I tend to mess with things I'm not supposed to," Kaçar said. "Locked in time? Let's unlock it. Breaking it would lead the cell to destruction? Let's break it."

The researchers took six different strains of Escherichia coli bacteria and genetically engineered the cells with mutated components of their translational machinery. They targeted the step that feeds the unit with genetic information by swapping the shuttle protein with evolutionary cousins taken from other microbes, including a reconstructed ancestor from about 700 million years ago.

"We get into the heart of the heart of what we think is one of the earliest machineries of life," Kaçar said. "We purposely break it a little, and a lot, to see how the cells deal with this problem. In doing this, we think we create an urgent problem for the cell, and it will fix that."

Next, the team mimicked evolution by having the manipulated bacterial strains compete with each other - like a microbial version of "The Hunger Games." A thousand generations later, some strains fared better than others, as was expected. But when Kaçar's team analyzed exactly how the bacteria responded to perturbations in their translational components, they discovered something unexpected: Initially, natural selection improved the compromised translational machinery, but its focus shifted away to other cellular modules before the machinery's performance was fully restored.

To find out why, Kaçar enlisted Sandeep Venkataram, a population genetics expert at the University of California, San Diego.

Venkataram likens the process to a game of whack-a-mole, with each mole representing a cellular module. Whenever a module experiences a mutation, it pops up. The hammer smashing it back down is the action of natural selection. Mutations are randomly spread across all modules, so that all moles pop up randomly.

"We expected that the hammer of natural selection also comes down randomly, but that is not what we found," he said. "Rather, it does not act randomly but has a strong bias, favoring those mutations that provide the largest fitness advantage while it smashes down other less beneficial mutations, even though they also provide a benefit to the organism."

In other words, evolution is not a multitasker when it comes to fixing problems.

"It seems that evolution is myopic," Venkataram said. "It focuses on the most immediate problem, puts a Band-Aid on and then it moves on to the next problem, without thoroughly finishing the problem it was working on before."

"It turns out the cells do fix their problems but not in the way we might fix them," Kaçar added. "In a way, it's a bit like organizing a delivery truck as it drives down a bumpy road. You can stack and organize only so many boxes at a time before they inevitably get jumbled around. You never really get the chance to make any large, orderly arrangement."

Why natural selection acts in this way remains to be studied, but what the research showed is that, overall, the process results in what the authors call "evolutionary stalling" - while evolution is busy fixing one problem, it does at the expense of all other issues that need fixing. They conclude that at least in rapidly evolving populations, such as bacteria, adaptation in some modules would stall despite the availability of beneficial mutations. This results in a situation in which organisms can never reach a fully optimized state.

"The system has to be capable of being less than optimal so that evolution has something to act on in the face of disturbance - in other words, there needs to be room for improvement," Kaçar said.

Kaçar believes this feature of evolution may be a signature of any self-organizing system, and she suspects that this principle has counterparts at all levels of biological hierarchy, going back to life's beginnings, possibly even to prebiotic times when life had not yet materialized.

With continued funding from the John Templeton Foundation and NASA, the research group is now working on using ancestral sequencing to go back even further in time, Kaçar said.

"We want to strip things down even more and create systems that start out as what we would consider pre-life and then transition into what we consider life."

Credit: 
University of Arizona

Big dogs face more joint problems if neutered early

Heavier mixed-breed dogs have higher health risks if neutered or spayed early, according to a new study from researchers at the University of California, Davis. The study found mixed-breed dogs weighing more than 44 pounds as adults are at higher risk for one or more joint disorders if neutered before 1 year of age. Dogs weighing up to 43 pounds had no increased risk for joint problems. The study was published in the journal Frontiers in Veterinary Science.

It's standard practice in the U.S. and much of Europe to neuter dogs by 6 months of age. This study, which analyzed 15 years of data from thousands of dogs at UC Davis Veterinary Medical Teaching Hospital, suggests dog owners should consider their options carefully.

"Most dogs are mixed breeds," said lead author Benjamin Hart, distinguished professor emeritus at the UC Davis School of Veterinary Medicine. "We hope this study will influence the spay or neuter process in order to give people wishing to adopt a puppy the time to make an informed decision on when to spay or neuter."

Researchers examined common joint disorders including hip dysplasia, elbow dysplasia and cranial cruciate ligament tears, a knee injury, in five weight categories. They also looked at risks of mixed-breed dogs developing cancers based on weight but found no increased risk in any weight category compared to intact dogs.

The risk of joint disorders for heavier dogs can be up to a few times higher compared to dogs left intact. This was true for large mixed-breed dogs. For example, for female dogs over 43 pounds, the risk jumped from 4 percent for intact dogs to 10-12 percent if spayed before a year of age.

NEUTERING POLICIES SHOULD BE REVIEWED

"The study raises unique challenges," noted co-author Lynette Hart, professor at the UC Davis School of Veterinary Medicine. "People like to adopt puppies from shelters, but with mixed breeds it may be difficult to determine just how big the dog will become if you don't know anything about the dog's parents."

Neutering prior to adoption is a common requirement or policy of humane societies, animal shelters and breeders. The authors suggested the policy be reviewed and modified appropriately. Shelters, breeders and humane societies should consider adopting a standard of neutering at over a year of age for dogs that will grow into large sizes.

Lynette Hart said the study is especially relevant for people and organizations raising service dogs.

"They need to take a serious look at this," said Hart. "Joint disorders can shorten a dog's useful working life and impact its role as a family member."

A previous study conducted by the UC Davis researchers found health risks based on neuter age varied greatly depending on the breed of the dog.

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University of California - Davis

Research recommends integrated approaches to managing reniform nematodes in cotton

While there are many pests affecting cotton, the reniform nematode is one the most damaging, with the ability to cause annual losses of approximately $33 million within the Mid-Southern United States. Farmers struggle to manage this pest as commercially available resistance is not widespread and a limited number of products are commercially available for use in suppressing the reniform nematode.

The reniform nematode is prevalent in Mississippi, especially in fields with silt loam soil classes, where current management plans involve a carousel of strategies, including rotation, seed-applied nematicides, in-furrow nematicides that are difficult to obtain, or the costly application of an in-furrow fumigant. Cotton farmers who rely on income from farming may find themselves in a situation where reniform nematode management costs outweigh the money earned from cotton sales.

In a recent study, researchers based at Mississippi State University set out to determine the most effective management approach that would maintain economical cotton yield and reduce losses that result from the reniform nematode. Their research made comparisons between either seed-applied nematicides, in-furrow nematicides, or a soil fumigant application. The research also explored integrated forms of management and considered how seed-applied nematicides and in-furrow nematicides worked together.

"We determined that seed-applied nematicides were better than the base fungicide seed treatment package without nematicide, but that one seed applied nematicide in particular coupled with an in-furrow nematicide produced yield that was almost equal to the in-furrow soil fumigant," explained Tom Allen, who works out of the Delta Research and Extension Center in Stoneville, Mississippi. "We also determined that even when adding multiple nematode-related treatments together that cotton yield could be improved and still remain economically advantageous."

However, in situations where the in-furrow fumigant was used, production costs were deemed too expensive and risk-averse. According to Allen, "The biggest takeaway is that, in situations with reniform nematode pressure above the economic threshold, cotton farmers can economically manage the nematode with an in-furrow nematicide to reduce early-season threats from the nematode."

Credit: 
American Phytopathological Society

Many medical 'rainy day' accounts aren't getting opened or filled, study finds

One-third of the people who could benefit from a special type of savings account to cushion the blow of their health plan deductible aren't doing so, according to a new study.

And even among people who do open a health savings account (HSA), half haven't put any money into it in the past year. This means they may be missing a chance to avoid taxes on money that they can use to pay for their health insurance deductible and other health costs.

The study also finds that those who buy their health insurance themselves, and select a high-deductible plan on an exchange such as http://www.healthcare.gov, are less likely to open an HSA than those who get their insurance from employers who offer only a high-deductible option.

HSAs are different from the flexible spending accounts that some employers offer. HSAs can only be opened by people in health plans that require them to pay a deductible of $1,400 for an individual or $2,800 for a family before their insurance benefits kick in.

In a new paper in JAMA Network Open, a team led by researchers at the University of Michigan and VA Ann Arbor Healthcare System reports results from a national survey of more than 1,600 participants in high-deductible health plans.

Key findings

They note that half of those who had an HSA and put money into their account in the past year had socked away $2,000 or more. And among those who hadn't put money in, 40% said it was because they already had enough savings to cover their costs.

But those with lower levels of education were much less likely to have opened an HSA, and to have contributed to it even if they did open one. Those with lower levels of understanding of health insurance concepts, called health insurance literacy, were also less likely to put money in their HSA if they had one.

And one-third of those who didn't put money into their HSA said it was because they couldn't afford to save up for health costs.

"These findings are concerning, given that nearly half of Americans with private insurance now have high-deductible plans," says Jeffrey Kullgren, M.D., M.S., MPH, who led the study and has done other research on HDHPs and health care consumerism. "While policymakers have focused on expanding availability and permitted uses of HSAs, and increasing how much money they can hold, work is needed to help eligible enrollees open them and use them to get the care they need at a price they can afford."

Change needed

In the new paper and in a report from the U-M Institute for Healthcare Policy and Innovation, Kullgren and his colleagues call for more efforts to increase uptake of HSAs, and contributions to HSAs, by employers, health insurers and the health systems that provide care and bill insurers for that care.

Targeted interventions, especially those aimed at people with lower levels of education or health insurance literacy, should be developed.

The researchers note that as federal and state exchanges prepare to open for 2021 enrollment, expanding the types of exchange plans that are eligible to be linked to an HSA will be important. Currently, just 7% of the plans bought on exchanges are eligible for an HSA, even though many exchange plans come with a high deductible.

The study data come from an online survey of English-speaking adults under age 65; the study population was weighted to include a higher proportion of people with chronic health conditions than the national population.

For the survey, the researchers asked respondents about HSAs using the National Health Interview Survey definition of an HSA as "a special account or fund that can be used to pay for medical expenses" that are "sometimes referred to as Health Savings Accounts (HSAs), Health Reimbursement Accounts (HRAs), Personal Care accounts, Personal Medical funds, or Choice funds, and are different from Flexible Spending Accounts."

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Michigan Medicine - University of Michigan

Waistline matters in kidney disease

Obesity as assessed by body mass index is associated with an increased risk of heart disease and progression of kidney disease in those with chronic kidney disease (CKD). In this cohort of patients with CKD, Sankar D. Navaneethan et al studied whether different obesity measures such as intra-abdominal fat, liver fat, and subcutaneous fat (obtained using an MRI scan) were associated with known cardiometabolic risk factors. The authors further assessed whether physical function (measured using a 400m walk test) was independently associated with the same cardiometabolic risk factors. Their analysis suggests that all measures of higher fat content were associated with an increased level of cardiometabolic risk factors. While slower walk time were associated with an increased level of cardiometabolic risk factors, it did not modify the associations between fat measures and these risk factors. In summary, these data highlight that various abdominal fat measures and lower physical fitness levels are associated with a higher cardiovascular risk in those with CKD

Credit: 
National Kidney Foundation

Radiation to treat pediatric cancers may have lasting impact on heart and metabolic health

Bottom Line: Adult survivors of childhood abdominal and pelvic cancers who had been treated with radiation therapy experienced abnormalities in body composition and had worse cardiometabolic health compared with the general population.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Carmen Wilson, PhD, assistant member in the Epidemiology and Cancer Control department at St. Jude Children's Research Hospital

Background: "Body composition abnormalities and cardiometabolic impairments are of concern among survivors given that in the general population, these conditions increase the risk of developing life-threatening diseases including cardiovascular disease and type 2 diabetes," said Wilson. The impacts of radiation therapy on metabolic health have been previously reported for survivors of pediatric leukemia, brain tumors, and hematopoietic stem cell transplants, but the impacts on survivors of pediatric abdominal and pelvic tumors remained unclear, she said.

How the Study was Conducted: In this study, Wilson and colleagues assessed 431 adult survivors of pediatric abdominal or pelvic solid tumors who had been previously treated at St. Jude Children's Research Hospital. The median age of participants during the study was 29.9 years. The most frequent childhood diagnoses were neuroblastoma, Wilms tumor, and germ cell tumor, and the median age of participants at diagnosis was 3.6 years. Approximately 37 and 36 percent of participants had received abdominal and pelvic radiation therapy, respectively, as part of their treatment.

To assess the impacts of radiation therapy, the authors compared the participants' body composition, metabolic abnormalities, and physical function to those of the general population, using age-, sex-, and ethnicity-matched data from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES).

Results: Wilson and colleagues found that compared with data from NHANES, the survivors in their study were significantly more likely to have insulin resistance (33.8 percent vs. 40.6 percent), high triglycerides (10.02 percent vs. 18.4 percent), and low levels of high-density lipoproteins, commonly referred to as "good cholesterol" (28.9 percent vs. 33.5 percent). There were no significant differences in the levels of low-density lipoproteins ("bad cholesterol") between survivors and the general population.

The analyses also demonstrated that survivors of abdominal and pelvic solid tumors had lower relative lean body mass than the general population and that the lower relative lean body mass was associated with the dose of prior abdominal or pelvic radiation. Lean body mass, which measures the non-fat content of the body, is related to basal metabolic rate; therefore, an individual with lower lean body mass burns fewer calories while resting than someone with higher lean body mass, Wilson explained.

There was no significant difference in relative fat body mass between survivors and the general population; however, survivors who had high relative fat mass had reduced quadricep strength and poor physical performance (as measured by a sit-and-reach test and distance covered during a six-minute walk) compared with survivors who had low relative fat mass.

Author's Comments: "It is possible that abdominal and pelvic-directed radiation therapy damages postural muscles or subtly impairs sex hormone production, ultimately affecting muscle mass," said Wilson. She explained that radiation therapy has been shown to cause muscle injury, resulting in muscle fiber loss and loss of muscle regenerative cells, in animal studies. Wilson added that lifestyle choices may also impact relative lean mass and cardiometabolic health among survivors.

Wilson suggested that future research could examine the impact of radiation therapy and other cancer treatments on fat distribution across the body since increased abdominal obesity has been shown to be a better predictor of adverse health effects than measures of overall obesity.

In addition, Wilson is interested in exploring how interventions directed at lifestyle behaviors could improve lean mass and decrease fat mass among survivors of pediatric cancers. "While it may not be possible to avoid radiation therapy as a key treatment for many solid tumors, early research suggests that resistance training interventions in survivors increase lean mass," said Wilson. "Further work is needed to see if training would also impact cardiometabolic impairments in this population."

Study Limitations: A limitation of the study is that cardiometabolic outcomes may have been measured differently in the study cohort compared with those surveyed by NHANES.

Credit: 
American Association for Cancer Research

Insect diversity boosted by combination of crop diversity and semi-natural habitats

To enhance the number of beneficial insect species in agricultural land, preserving semi-natural habitats and promoting crop diversity are both needed, according to new research published in the British Ecological Society's Journal of Applied of Ecology.

The study, by researchers in Sweden, the UK, Italy, Germany, Spain and France, found that increasing the diversity of crops in agricultural landscapes increased the diversity of beneficial insects such as pollinators. However, this benefit was only seen in landscapes with high proportions of semi-natural habitats such as forests and grassland.

In landscapes with both high crop diversity and semi-natural habitat cover, the researchers observed an increased diversity of ground beetle species as well as pollinators like bees and hoverflies. These insects have the potential to benefit crops through predating pests or pollinating flowering crop plants, both important for crop yields.

The same effects were not found for spiders, which surprised the researchers. "We expected pollinators to benefit because they are a highly mobile species, but the difference between ground beetles and spiders is harder to explain since both share similar adaptations to inhabit local crops." said Guillermo Aguilera of the Swedish University of Agricultural Sciences and lead author of the study.

Many beneficial insects and invertebrates are in decline, partly due to intensive crop management practices and a loss of semi-natural habitats from agriculture land, meaning the results have important implications. Guillermo Aguilera said: "We show that increasing local insect communities is possible in landscapes with semi-natural habitats by increasing crop diversity. Therefore, reducing the arable land and increasing semi-natural habitats is not always the only way for obtaining benefits from insects."

Insects and other invertebrates provide important ecosystem services. "Ground beetles and spiders are predators of species that can become pests. Wild pollinators have one of the most important roles in flowering crops. Both services, pest control and pollination, are important for the final crop yield." explains Guillermo Aguilera.

A greater diversity of crops may benefit pollinators through giving them a more varied and continuous food source. Oilseed rape, the most abundant flowering crop in the study area, provides massive resources for pollinators. However, its flowers are only open for a short period of time. Growing other crops that flower throughout the year could help support pollinators.

Semi-natural habitats provide nesting sites and additional food for both pollinators and predators. They're likely to be particularly beneficial to mobile species of ground beetles which often colonise crop fields from these habitats.

The researchers compiled data from seven previous studies that looked at invertebrate abundances in crop fields. The data spanned 154 crop fields in southern Sweden, an area consisting of arable land and semi-natural habitats, like grassland and woodland, between 2007 and 2017.

"The ultimate goal was to investigate the effect of crop diversity in the landscape with local communities of invertebrates" said Guillermo Aguilera. "After obtaining the invertebrate information and the coordinates of the fields where they were collected, we analysed the diversity of crops present in the landscape at the time of the sampling as well as the amount of semi-natural habitats such as grasslands."

The research focussed on southern Sweden, the most agriculturally important region in the country in terms of crop production. While this gave the researchers a large study area, they acknowledge that it's hard to generalise the results to a more global landscape.

Guillermo Aguilera said "It would be interesting to see what happens in other landscapes with a higher crop diversity by default than Sweden. It would also be interesting to look at how invertebrate communities respond to other forms of diversification in agriculture landscapes. For instance, the management of certain crops is something that can vary a lot between countries or regions."

Credit: 
British Ecological Society

'Madsen' wheat as source of disease resistance

image: Madsen, growing next to lines which have it as a parent, in the Palouse region of Washington state.

Image: 
courtesy of Arron Carter

A plant breeder's goal is to release cultivars that are commercially economical and environmentally sustainable. Breeders never know how well new cultivars will perform under commercial production until they are released and grown across different environments.

In an article recently published in the Journal of Plant Registrations, a journal of the Crop Science Society of America, researchers examined the impact the cultivar 'Madsen' on Pacific Northwest wheat, as well as other national and international breeding programs. Madsen has been grown in the Pacific Northwest for over 30 years--it was the most widely grown wheat cultivar from 1991 until 2004. It was found that of the new cultivars that were replacing Madsen in production, many of them had Madsen as a parent of the cultivar.

Madsen was released because of its resistance to strawbreaker foot rot and stripe rust, both of which are fungal diseases. Through subsequent research, Madsen was also found to be resistant to nematodes and Wheat yellow mosaic virus, and moderately resistant to common bunt and powdery mildew. Although not fully resistant, it was also less susceptible than other commercially available cultivars to stresses like low pH soils and Cephalosporium stripe.

The excellent resistance to biotic and abiotic stress of Madsen contributed to its widespread success in the Pacific Northwest, and has also allowed it to be used in breeding programs across the globe to protect the wheat crop against many diseases which threaten global food security.

Credit: 
American Society of Agronomy

PAD patients with depression had worse recovery, women twice as likely to be depressed

DALLAS, Aug. 12, 2020 — Patients with peripheral artery disease (PAD) and depressive symptoms experience worse recovery especially women, compared to counterparts without depressive symptoms, one year after receiving specialty care for PAD,  according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

PAD is a narrowing of the peripheral arteries serving the legs, stomach, arms and head, and most commonly affects arteries in the legs. PAD is associated with a high risk of death and illness from cardiovascular diseases and is a significant global health problem that may cause excruciating pain while walking and may impact mobility, functioning, health status and quality of life.  

“This is the first study to document how depressive symptoms may complicate PAD recovery even among patients receiving specialty care,” said senior study author Kim G. Smolderen, Ph.D., FAHA, a clinical health psychologist and co-director of the Vascular Medicine Outcomes Research Program in the internal medicine department at Yale New Haven Hospital, Yale University School of Medicine in New Haven, Connecticut. 

For one year, researchers followed 1,243 patients treated at vascular specialty clinics in the U.S., the Netherlands and Australia who were being treated for new or recurrent symptoms of PAD. Patients included in the study (average age 67, 38% women) were enrolled from the Patient-centered Outcomes Related to Treatment Practices in Peripheral Artery Disease Investigating Trajectories (PORTRAIT) Registry. The international registry addresses gaps in knowledge about the quality of care and health outcomes of patients with PAD, especially as seen from the patients’ perspectives.

Researchers assessed depressive symptoms at the beginning of the study using the standard 8-item Patient Health Questionnaire (PHQ-8). Patients rated statements about how often they:

have “little interest or pleasure in doing things;”
feel “down, depressed or hopeless;”
have “trouble sleeping;”
feel ”tired/no energy,”
have “poor appetite or overeat;”
feel “bad about yourself;” or
believe they are “moving or speaking so slowly that other people notice/or the opposite, being so fidgety or restless that they have to move around a lot more than usual.“

Disease-specific and general health status were measured at the beginning of the study and at three, six and 12 months later with standardized patient interviews.

The researchers then reconstructed the one-year health status trajectory by whether or not patients reported depressive symptoms when they were diagnosed with PAD.  The analysis found:

Men and women with depressive symptoms had worse health status at each time point, compared to patients who did not report such symptoms.
More women than men, had depressive symptoms, 21.1% vs. 12.9%, respectively.
One in five women with a new diagnosis or worsening symptoms of PAD may have clinically relevant depressive symptoms one year after diagnosis, approximately two times higher than men.  The women experienced worse health status outcomes that are partially explained by depressive symptoms.

“A major goal of PAD treatment is improving patients’ health status and quality of life,” said study first author Qurat-Ul-Ain Jelani, M.D., an interventional cardiologist in training at Yale University School of Medicine. “Not recognizing or treating depressive symptoms may stand in the way of realizing optimal recovery.   

“As more value-based care options are designed for patients with PAD, integrating mental health screening and treatment pathways into chronic disease management may increase the opportunity for patients to receive more holistic care, thus improving outcomes. A multidisciplinary approach that includes mental health supports for patients with PAD would be beneficial.”

Because the study was focused on patients treated at vascular specialty clinics, the findings may not be representative of the general PAD population who may not have access to specialty care. Researchers also acknowledged that the emphasis on depressive symptoms excludes many mental health concerns, such as anxiety or stress, and also excludes unmeasured clinical factors that could contribute to depressive symptoms.

“PAD is more than treating the legs and the corresponding pain,” Smolderen said. “We need awareness for the patient as a whole in order to provide patient-centric care.”

Credit: 
American Heart Association

Research suggests bias against natural hair limits job opportunities for black women

image: Ashleigh Shelby Rosette, a management professor and a senior associate dean at Duke University's Fuqua School of Business, led the research.

Image: 
Duke University

New research suggests Black women with natural hairstyles, such as curly afros, braids or twists, are often perceived as less professional than Black women with straightened hair, particularly in industries where norms dictate a more conservative appearance.

The findings, published in the journal Social Psychological and Personality Science, offer empirical evidence that societal bias against natural Black hairstyles infiltrates the workplace and perpetuates race discrimination, said Ashleigh Shelby Rosette, a management professor and a senior associate dean who conducted the research at Duke University's Fuqua School of Business.

The impact of a woman's hairstyle may seem minute, Rosette said, "but for Black women, it's a serious consideration and may contribute to the lack of representation for Blacks in some organizational settings. In the aftermath of the George Floyd murder and the corresponding protests, many organizations have rightly focused on tactics to help eradicate racism at systemic and structural levels. But our individually held biases often precede the type of racist practices that become embedded and normalized within organizations."

To detect bias against Black women with natural hair, the researchers recruited participants of different races and asked them to assume the role of recruiters screening job candidates.

Participants were given profiles of Black and white female job candidates and asked to rate them on professionalism, competence and other factors. Black women with natural hairstyles received lower scores on professionalism and competence and were not recommended as frequently for interviews compared with three other types of candidates: Black women with straightened hair and white women with curly or straight hair, the researchers found.

"In many Western societies, whites have historically been the dominant social group and, as a result, the standard for professional appearance is often based on the physical appearance of whites. For women's hair, that benchmark is having straightened hair," said Rosette, who collaborated with Christy Zhou Koval, a Fuqua alumna and assistant professor at Michigan State University.

Some straightening processes can cost hundreds to thousands of dollars and can cause hair breakage, scalp disease and other health complications, Rosette noted.

"When a Black woman chooses to straighten her hair, it should be a personal preference, not a burden to conform to a set of criteria for which there could be adverse consequences," she said.

In one experiment, two groups of participants evaluated the exact same job candidate, who was a Black woman. One group saw a photo of the candidate with natural hair while the other group saw her with straight hair. The group who saw a candidate with straight hair rated her as more professional -- defined as more polished, refined and respectable -- and they more strongly recommended her for an interview.

The fictional job candidates with natural hair were subject to discrimination when they were being evaluated for jobs in consulting, an industry with conservative dress norms.

However, when participants considered profiles of women who wanted to work at an ad agency, the candidate's hair texture didn't affect perceptions of professionalism or whether they were recommended for interviews. This may be because advertising is viewed as a more creative industry than consulting with less rigid dress norms, the authors posited.

"Some organizations strip away biographical information such as a person's name and other clues about gender or race from application materials. This procedure is known as blinding and has been shown to reduce similar types of bias as what we found in our research," she said. "But there fundamentally has to be a level of awareness that the natural hair bias exists. If you don't know that it exists, you can't know its influence on your decision-making processes."

It was only three years ago that the U.S. Army eased restrictions on natural hairstyles for Black soldiers, Rosette noted. In recent months, several cities and states have passed laws prohibiting discrimination against natural hairstyles for Black people at work and public school. Federal legislators have drafted similar bills to ban hair-based race discrimination under U.S. law.

"Although there have been some policy changes protecting Black people from discrimination based on their natural hair, these changes are fairly recent and not as widely implemented as they should be," Rosette said. "This work illustrates that racial discrimination based on hair can occur, and we hope it can inform new policies and practices for firms to ensure they're considering candidates equally, and furthermore, aren't missing out on top talent."

Credit: 
Duke University

Meditation-relaxation therapy may offer escape from the terror of sleep paralysis

Sleep paralysis - a condition thought to explain a number of mysterious experiences including alleged cases of alien abduction and demonic night-time visits - could be treated using a technique of meditation-relaxation, suggests a pilot study published today.

Sleep paralysis is a state involving paralysis of the skeletal muscles that occurs at the onset of sleep or just before waking. While temporarily immobilised, the individual is acutely aware of their surroundings. People who experience the phenomenon often report being terrorised by dangerous bedroom intruders, often reaching for supernatural explanations such as ghosts, demons and even alien abduction. Unsurprisingly, it can be a terrifying experience.

As many as one in five people experiences sleep paralysis, which may be triggered by sleep deprivation, and is more frequent in psychiatric conditions like post-traumatic stress disorder. It is also common in narcolepsy, a sleep disorder involving excessive daytime sleepiness and sudden loss of muscle control.

Despite the condition being known about for some time, to date there are no empirically-based treatments or published clinical trials for the condition.

Today, in the journal Frontiers in Neurology, a team of researchers report a pilot study of meditation-relaxation therapy involving 10 patients with narcolepsy, all of whom experience sleep paralysis.

The therapy was originally developed by Dr Baland Jalal from the Department of Psychiatry, University of Cambridge. The current study was led by Dr Jalal and conducted in collaboration with Dr Giuseppe Plazzi's group at the Department of Biomedical and Neuromotor Sciences, University of Bologna/IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy.

The therapy teaches patients to follow four steps during an episode:

1. Reappraisal of the meaning of the attack - reminding themselves that the experience is common, benign, and temporary, and that the hallucinations are a typical by-product of dreaming

2. Psychological and emotional distancing - reminding themselves that there is no reason to be afraid or worried and that fear and worry will only make the episode worse

3. Inward focused-attention meditation - focusing their attention inward on an emotionally-involving, positive object (such as a memory of a loved one or event, a hymn/prayer, God)

4. Muscle relaxation - relaxing their muscles, avoiding controlling their breathing and under no circumstances attempting to move

Participants were instructed to keep a daily journal for four weeks to assess sleep paralysis occurrence, duration and emotions. Overall, among the 10 patients, two-thirds of cases (66%) reported hallucinations, often upon awakening from sleep (51%), and less frequently upon falling asleep (14%) as rated during the first four weeks.

After the four weeks, six participants completed mood/anxiety questionnaires and were taught the therapy techniques and instructed to rehearse these during ordinary wakefulness, twice a week for 15 min. The treatment lasted eight weeks.

In the first four weeks of the study, participants in the meditation-relaxation group experienced sleep paralysis on average 14 times over 11 days. The reported disturbance caused by their sleep paralysis hallucinations was 7.3 (rated on a ten-point scale with higher scores indicating greater severity).

In the final month of the therapy, the number of days with sleep paralysis fell to 5.5 (down 50%) and the total number of episodes fell to 6.5 (down 54%). There was also a notable tendency towards reductions in the disturbance caused by hallucinations with ratings dropping from 7.3 to 4.8.

A control group of four participants followed the same procedure, except participants engaged in deep breathing instead of the therapy - taking slow deep breaths, while repeatedly counting from one to ten.

In the control group, the number of days with sleep paralysis (4.3 per month at the start) was unchanged, as well as their total number of episodes (4.5 per month initially). The disturbance caused by hallucinations was likewise unchanged (rated 4 during the first four weeks).

"Although our study only involved a small number of patients, we can be cautiously optimistic of its success," said Dr Jalal. "Meditation-relaxation therapy led to a dramatic fall in the number of times patients experienced sleep paralysis, and when they did, they tended to find the notoriously terrorising hallucinations less disturbing. Experiencing less of something as disturbing as sleep paralysis is a step in the right direction."

If the researchers are able to replicate their findings in a larger number of people - including those from the general population, not affected by narcolepsy - then this could offer a relatively simple treatment that could be delivered online or via a smartphone to help patients cope with the condition.

"I know first-hand how terrifying sleep paralysis can be, having experienced it many times myself," said Dr Jalal. "But for some people, the fear that it can instil in them can be extremely unpleasant, and going to bed, which should be a relaxing experience, can become fraught with terror. This is what motivated me to devise this intervention."

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University of Cambridge

How anxiety--and hope--can drive new product adoption

Researchers from University of New South Wales, University of Southern California, and Imperial College London published a new paper in the Journal of Marketing that analyzes how varying levels of hope and anxiety about outcomes from new products affect consequential adoption intentions and actual product adoption.

The study, forthcoming in the Journal of Marketing, is titled "Strong Anxiety Boosts New Product Adoption When Hope Is Also Strong" and is authored by Yu-Ting Lin, Deborah J. MacInnis, and Andreas B. Eisingerich.

New products offer consumers the opportunity to create positive outcomes that are congruent with the goals they hope to achieve. However, because they are new and untried, new products might also create anxiety about outcomes that are incongruent with consumers' goals. The research team demonstrates that strong anxiety about outcomes from a new product actually enhances (vs. weakens) consequential adoption intentions toward and actual adoption of that new product when hope is also strong. Lin explains that "We show that this effect occurs because strong hope and strong anxiety motivate individuals to engage in action planning--that is, to contemplate actions that support the occurrence of hoped-for outcomes and actions that avoid the occurrence of anxiety-arousing ones." Action planning boosts new product adoption by enhancing consumers' perceived control over outcomes from new product adoption. These findings aid marketers in understanding how emotions like hope and anxiety can affect new product adoption. They also aid policymakers by suggesting that disclaimers that make consumers anxious about potentially negative outcomes from new product purchase or usage could encourage thoughtful processing in the form of action planning when hope is also strong.

Specifically, if market research reveals that consumers already have strong anxiety about outcomes from new product adoption, marketing communications should emphasize the product's relevance to the goals that consumers hope for, as opposed to downplaying consumers' anxiety about potential adverse outcomes. Conversely, if market research reveals that consumers have strong hope for the product but low anxiety, the results suggest that marketers might benefit by providing warning labels, disclaimers, and disclosures. Beyond encouraging new product adoption, such communications could also enhance product satisfaction. MacInnis adds, "In other words, to the extent that consumers consider goal-incongruent outcomes and plan for how they can be avoided, they may ultimately be more satisfied with the product than would consumers who never considered potential anxiety-evoking outcomes or engaged in action planning."

Relatedly, and from a public policy perspective, the findings suggest that disclosures or labels that evoke strong anxiety about goal-incongruent outcomes from new product use might encourage more thoughtful decision making when hope is also strong. Whereas marketers may be loath to use such disclaimers, this research suggests that when a new product evokes strong levels of hope, anxiety-inducing disclosures might not harm, and could potentially help, new product adoption.

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American Marketing Association

KIST finds a strong correlation between ultrasonic stroke rehabilitation treatment and brain waves

image: (A) Comparison of ipsilesional (left) and contralesional (right) normalized delta power between Stroke and LIFU group. (B) pdBSI in delta band comparison between Stroke and LIFU group. (denotes p < 0.05).

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Korea Institue of Science and Technology(KIST)

The Korea Institute of Science and Technology (KIST) announced that a research team led, by Dr. Hyungmin Kim at the Center for Bionics, Biomedical Research Institute of the KIST, found a strong correlation between a ultrasonic stroke rehabilitation method for treating damaged brain and a change in delta waves, which is a type of brain waves.

A stroke is the result of a cerebrovascular hemorrhage/infarction and is a disease with a high mortality rate. Even when a stroke does not lead to death, it results in the blockage of the affected person's blood supply and damage to the nerve cells, causing the impairment of physical movement. Many researches are underway on post-stroke rehabilitation methods that can be used to repair damaged brain.

Dr. Hyungmin Kim of the KIST recently published a study on hemiparalysis treatment for motor function recovery, a treatment in which the deep cerebellum is stimulated using low-intensity focused ultrasound stimulation (Neurorehabil Neural Repair. 2018 Sep;32(9):777-787). This treatment method, which can be used to treat stroke patients with various brain lesions, has received much attention as it does not require surgical procedures and can be used to selectively stimulate deeper parts of the brain areas.

To apply this method for various stroke treatments, a 'stimulation guide' is required. This can be used to assess the patient's prognosis after brain stimulation and to optimize the intensity and frequency of the stimulation for maximizing motor function recovery.

In order to develop such a guide, the KIST research team observed changes in the brain waves of the nerve cells of stroke lesions during treatment. In particular, the research team observed and analyzed changes in delta waves (1-4 Hz), which abnormally increase in brain lesions, in both the normal cerebral hemisphere and the cerebral hemisphere affected by the legion.

The KIST research conducted the ultrasound stimulation treatment on the deep cerebellum of mice for three days. On the first day, the motor functions of the mice improved almost three-fold, and on the fourth day, the mice were able to retain their improved motor functions. During the experiment, changes in the delta waves were observed, which increased up to three times, confirming that interhemispheric balance was retained and held steady at a normal level in the ultrasound stimulation group.

The study found that ultrasound stimulation can suppress delta waves and induce a change in damaged brain, signifying the improvement of motor functions. If a patient-specific ultrasound stimulation method can be developed by monitoring brain waves, this type of treatment can be translated from animal experimentation to actual patient treatment.

"Given that ultrasound brain stimulation progresses at a rapid pace and given that it is being studied in relation to various brain diseases, it will likely be used as an effective stroke treatment in the near future," said Dr. Hyungmin Kim of the KIST. "In order to develop an ultrasound stimulation treatment, it is essential to verify the safety of such treatment based on the careful observation and long-term tracking of various stimulation conditions."

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National Research Council of Science & Technology

Lipoic acid supplements help some obese but otherwise healthy people lose weight

CORVALLIS, Ore. - A compound given as a dietary supplement to overweight but otherwise healthy people in a clinical trial caused many of the patients to slim down, research by Oregon State University and Oregon Health & Science University showed.

The research, published in the Journal of Nutrition, analyzed the effects of 24 weeks of daily, 600-milligram doses of lipoic acid supplements on 31 people, with a similarly sized control group receiving a placebo.

"The data clearly showed a loss in body weight and body fat in people taking lipoic acid supplements," said Balz Frei, director emeritus of OSU's Linus Pauling Institute and one of the scientists on the study. "Particularly in women and in the heaviest participants."

Produced by both plants and animals, lipoic acid sets up shop in cells' mitochondria, where it's normally attached to proteins involved in energy and amino acid metabolism. A specialized, medium-chain fatty acid, it's unique in having two sulfur atoms at one end of the chain, allowing for the transfer of electrons from other sources.

The body generally produces enough lipoic acid to supply the enzymes whose proper function requires it. When taken as a dietary supplement, lipoic acid displays additional properties that might be unrelated to the function in the mitochondria. They include the stimulation of glucose metabolism, antioxidant defenses and anti-inflammatory responses - making it a possible complementary treatment for people with diabetes, heart disease and age-related cognitive decline.

"Scientists have been researching the potential health benefits of lipoic acid supplements for decades, including how it might enhance healthy aging and mitigate cardiovascular disease," said Alexander Michels, another Linus Pauling Institute scientist involved with the study. "In both rodent models and small-scale human clinical trials, researchers at the LPI have demonstrated the beneficial effects of lipoic acid on oxidative stress, lipid metabolism and circadian rhythm."

The OSU/OHSU project addressed two issues commonly ignored by previous human trials, said Tory Hagen, a professor of biochemistry and biophysics in the OSU College of Science and the study's corresponding author.

"Many existing clinical studies using lipoic acid have focused on volunteers with pre-existing conditions like diabetes, making it difficult to determine if lipoic acid supplements simply act as a disease treatment or have other beneficial health effects," said Hagen, principal investigator and Helen P. Rumbel Professor for Healthy Aging Research at the institute. "Another issue is the formulation of the supplement. Many previous studies have used the S form of lipoic acid, which is a product of industrial synthesis and not found in nature. We only used the R form of lipoic acid - the form found in the body naturally."

Contrary to what was expected by the researchers, decreased levels of triglycerides - a type of fat, or lipid, found in the blood - were not seen in all the participants taking lipoic acid.

"The effect of lipoic acid supplements on blood lipids was limited," said Gerd Bobe, another LPI scientist who collaborated on the study. "But people who lost weight on lipoic acid also reduced their blood triglyceride levels - that effect was clear."

Other effects of the lipoic acid supplements were measurable as well.

"By the end of the study, some markers of inflammation declined," Hagen said. "The findings also suggest that lipoic acid supplementation provides a mild reduction in oxidative stress. It is not a perfect panacea, but our results show that lipoic acid supplements can be beneficial."

Identifying which patients will benefit the most from lipoic acid supplementation, and how much they need, is important for both clinical and economic reasons, he added.

"Lipoic acid supplements are often quite expensive," he said. "So understanding how we can maximize benefits with smaller amounts of the supplement is something we are interested in pursuing."

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Oregon State University