Earth

PENTEC: World experts team up to improve outcomes for children after radiation therapy

Annually, more than 350,000 children in the world are affected by pediatric cancer. Radiation has improved outcomes dramatically, but the damage caused to healthy tissue can affect the long-term health of a child. While clinicians and radiation specialists design treatments using the most up-to-date information available, there hasn't been a single guiding source of data to make evidence-based decisions that are specific for children. Now, a volunteer international research collaboration is working toward providing evidence-based guidelines for radiation therapy dosing for children. Results from this effort will help in minimizing side effects while continuing to provide effective radiation therapy.

An introduction to PENTEC--or Pediatric Normal Tissue Effects in the Clinic--was recently published in the International Journal of Radiation Oncology. PENTEC is made up of more than 150 physicians, medical physicists, epidemiologists and other specialists, who volunteer their time and expertise.

"This is really a labor of love," says Arthur Olch, PhD, a Medical Physicist at Children's Hospital Los Angeles. "We are all professionals and specialists, but we're also just people who care about what happens to these kids after their cancers are treated." In the Cancer and Blood Disease Institute at Children's Hospital Los Angeles, Dr. Olch works closely with radiation oncologists to help plan radiation therapy treatments and ensure radiation equipment is operating properly. He is also on the steering committee of PENTEC.

PENTEC is organized into 18 research groups, or "task forces," each of which focuses on how radiation affects a particular organ system--like the lungs and respiratory pathway, or the central nervous system. The group then scours the medical literature for studies and articles that report doses and outcomes. This often means reviewing hundreds of articles. After surveying the literature and compiling information about dosage and outcomes, they can correlate the side effects with the radiation dose to each organ.

"We are collecting a huge amount of information, which allows us to make recommendations about safe dosing to the pediatric radiation oncology community that's backed by evidence" says Dr. Olch.

But PENTEC's efforts don't end there. The team comes across many case studies that don't include enough information to contribute to the dose response curves. If, for example, a study reports on side effects but doesn't report on the radiation dose causing those effects, the study cannot be included. PENTEC hopes to change this; they propose reporting standards for future studies so that guidelines can be shaped by as much information as possible.

The specialists who volunteer with PENTEC have been working for several years on compiling enough information to formulate guidelines. This year, organ system task forces have started publishing their findings and recommendations and most should be published by the end of the year.

Dr. Olch believes PENTEC will lead to fewer life-altering side effects and improved quality of life for childhood cancer survivors in the future. "What we are doing has very broad implications," he says. "This will change the course of pediatric radiation therapy and hopefully lead to better outcomes for children with cancer--not just at Children's Hospital Los Angeles and in the United States, but worldwide."

Credit: 
Children's Hospital Los Angeles

Transferability of surface-functionalized metallic nanoparticles

Toxicity and Challenges in Transferability of Surface-functionalized Metallic Nanoparticles

https://doi.org/10.15212/bioi-2020-0047

Announcing a new article publication for BIO Integration journal. In this review the authors Muhammad Arif Asghar, Rabia Ismail Yousuf, Muhammad Harris Shoaib, Muhammad Arif Asghar and Nazish Mumtaz from Jinnah Sindh Medical University, Karachi, Pakistan, University of Karachi, Karachi, Pakistan, Food and Marine Resources Research Centre, Pakistan and Benazir Bhutto Shaheed University, Karachi, Pakistan discuss toxicity and challenges in transferability of surface-functionalized metallic nanoparticles from animal models to humans.

The unique size and surface morphology of nanoparticles (NPs) have substantially influenced all aspects of human life, making nanotechnology a novel and promising field for various applications in biomedical sciences.

Metallic NPs have garnered immense interest over the last few decades due to their promising optical, electrical, and biological properties. However, the aggregation and the toxic nature of these NPs have restricted their utilization in more optimized applications. The optimum selection of biopolymers and biological macromolecules for surface functionalization of metallic NPs will significantly improve their biological applicability and biocompatibility.

The authors review recent strategies involved in surface functionalization of metallic NPs, their specific biomedical applications, and comparison of their in vitro, ex vivo, and in vivo toxicities with non-functionalized metallic NPs and discuss the various challenges for metallic NPs to undergo human clinical trials

Credit: 
Compuscript Ltd

Adolescence is a window of opportunity for improving health literacy

image: Children taking part in LifeLab.

Image: 
University of Southampton

A study by the University of Southampton has shown its LifeLab programme, aimed at improving adolescent health through hands-on learning, significantly increases young people's understanding of what it means to lead a healthy lifestyle.

Led by a team from both the Faculty of Medicine and Education School at the University of Southampton, the LifeLab programme aims to encourage engagement with the science behind public health messages, to support development of health literacy alongside decision-making skills and promotion of adolescents' sense of control over their lives and futures. Based at University Hospital Southampton (UHS) NHS Foundation Trust, LifeLab is a state-of-the-art teaching laboratory dedicated to improving adolescent health through science engagement.

Latest research, published in the journal PLOS ONE1 and funded by the British Heart Foundation, has found that participation in LifeLab was associated with an increase in students' health literacy 12 months later. There was also evidence that participants subsequently judged their own lifestyles more critically than students who had not taken part in the programme.

Health literacy can be described as having the knowledge, skills, understanding and confidence to use health and care information and services and to apply these to lifestyle choices. Increasing evidence suggests that adolescence is a critical developmental stage during which lifelong health literacy can be established, offering a potential window of opportunity during which improvements in health literacy could benefit long-term health, and enable preparation for parenthood - passing on good health prospects to future children.

The randomised controlled trial was conducted in 38 secondary schools in England, drawing on principles of education, psychology and public health to engage students with science for health literacy, focused on the message 'Me, my health and my children's health'. The programme comprised a professional development day for teachers, a two to three week module of work for 13-14-year-olds and a 'hands-on' practical health science day visit to a dedicated facility in a university teaching hospital. Information was collected from 2929 adolescents aged 13-14 years, at baseline and 2487 at follow-up 12-months later.

"Experiencing LifeLab led to improved health literacy in adolescents and a move towards a more critical judgement of health behaviour 12 months after the intervention," said Dr Kath Woods-Townsend, who leads the LifeLab programme. "By providing opportunities linked to the National Curriculum, and which meet schools' needs, we have shown that students can be successfully engaged with the science behind the health messages, with lasting benefits for their health literacy."

Sharing her thoughts, Professor Hazel Inskip, principal investigator on the study from the Medical Research Council Lifecourse Epidemiology Unit at the University of Southampton, said: "The importance of health literacy in young people is being increasingly recognised, but there are very few randomised controlled trials seeking to assess interventions that promote health literacy through working in partnership with schools. It is an exciting step forwards to show that such a programme can engage adolescents with science, leading to sustained changes in health literacy and more critical judgement of their own behaviour."

Professor Keith Godfrey, a co-investigator on the study from the National Institute for Health Research Southampton Biomedical Research Centre, commented: "Interventions during adolescence have the potential for a 'triple dividend' of benefits now, into future adult life and for the next generation of children. The LifeLab programme paves the way for enabling young people to access, understand and reflect on what they need to do to live healthier lives."

Credit: 
University of Southampton

Southern African dinosaur had irregular growth

image: Reconstruction of Massospondylus carinatus

Image: 
Dorling Kindersley

Anyone who's raised a child or a pet will know just how fast and how steady their growth seems to be. You leave for a few days on a work trip and when you come home the child seems to have grown 10cm! That's all well and good for the modern household, but how did dinosaurs grow up? Did they, too, surprise their parents with their non-stop growth?

A new study lead by Dr Kimberley Chapelle of the American Museum of Natural History in New York City and Honorary Research Fellow at the University of the Witwatersrand suggests NOT. At least for one iconic southern African dinosaur species. By looking at the fossil thigh bones under a microscope, researchers can count growth lines, like those of a tree. This allows them to study how much the individuals grew each year. By looking at growth rings in the bones of Massospondylus carinatus, Dr Chapelle was able to show that its growth varied season-to-season, more like a tree than a puppy or a baby human.

"These things were just all over the show" said Chapelle, "one year they might gain 100kg of body weight and the next year they'd only grow by 10kg!"

Massospondylus was a medium sized dinosaur, up to 500kg in body weight, that lived in the Early Jurassic, so 200 million years ago. It fed on plants like ferns. The study suggests that Massospondylus' growth directly responded to its environmental conditions. In a good year with lots of rain and food, the species might race ahead, almost doubling their size. In a bad year where nutrients were scarce, it might hardly grow at all.

Chapelle and her colleagues suggest that such a growth strategy might have helped Massospondylus cope with the harsh environmental conditions following the end-Triassic Mass Extinction 200 million years ago, when more than 50% of species were wiped out.

"Massospondylus was one of the first Southern African dinosaurs named back in 1854 and we are still learning so much from it. It teaches us so much about our past environments and what southern Africa was like 200 million years ago" said Chapelle.

"This study shows the power of big sample sizes," said Jonah Choiniere, Professor at Wits University and co-author of the study, "when we can study a dinosaur from embryo to adult, like Massospondylus, we can begin to understand them as living animals."

"It is exciting to see such varied growth patterns in a dinosaur, showing us there is still so much to learn about these unique creatures!" said Dr Jennifer Botha from the National Museum, Bloemfontein, a co-author on the study.

Credit: 
University of the Witwatersrand

Using phage to discover new antifreeze proteins

image: Caption: Using viruses (phage display) to identify the one molecule in a billion (peptide8) that controls the formation of ice.

Image: 
University of Warwick

Controlling, and mitigating the effects of ice growth is crucial to protect infrastructure, help preserve frozen cells and to enhance texture of frozen foods. An international collaboration of Warwick Scientists working with researchers from Switzerland have used a phage display platform to discover new, small, peptides which function like larger antifreeze proteins. This presents a route to new, easier to synthesise, cryoprotectants.Caption: Using viruses (phage display) to identify the one molecule in a billion (peptide8) that controls the formation of ice. Credit: University of Warwick

Ice binding proteins, which includes antifreeze proteins, are produced by a large range of species from fish, to insects to plants, to prevent the damage caused by ice. The proteins achieve the remarkable function of recognizing and binding to ice, even in the huge excess of water (which ice is the solid form of). New antifreeze proteins have typically been discovered by isolation from the organisms.

In this work, the team took a very different approach by screening billions of possible peptides to find those which could bind to ice. This was achieved by Phage Display - a technology whereby a virus is used to generate vast numbers of peptides, and those which 'bind' to the ice can be isolated.

Using this a cyclic peptide of just 14 amino acids (which is very short compared to a typical protein) was discovered which could bind to ice. The team used computer simulations to understand how the peptide binds to the ice, which is not possible by 'wet' experimental techniques alone. The team also showed how this short peptide can be used to help purified other proteins by ace affinity purification.

By identifying these short peptides, it means researchers can now simply make (or buy) modified peptides to understand and probe how these interact with ice and help design new cryoprotectants with simplified structures, and hence lower cost.

In the paper "A Minimalistic Cyclic Ice-Binding Peptide from Phage Display", published in Nature Communications the international team including the University of Warwick and led by EPFL, Switzerland, have demonstrated the use of phage display to discover new minimalistic antifreeze peptides, which could not be achieved by conventional tools, which would not allow the billions of potential structures to be screened.

Dr Gabriele Sosso, Assistant Professor at the University of Warwick, in the Department of Chemistry comments:

"This work highlights that even very small changes within the structure of these peptides can make a huge difference in their ability to control the formation of ice. Our computer simulations allowed us to identify and understand the importance of these structural changes - which is a key step toward the rational design of synthetic cryoprotectants.

"It is such a privilege to be able to leverage both the experimental work of the Gibson's group and the computational resources of the SCRTP. Truly, Warwick is a great place to be if you want to understand how ice forms and what can we do to have a say in this process."

Professor Matthew Gibson, Professor at the University of Warwick in the Department of Chemistry and Warwick Medical School adds:

"We have been working on developing synthetic tools to understand, and interfere with, ice growth processes with an aim of helping develop new cryoprotectants. This work was really exciting, as we made use of biotechnology tools (phage) to discover small, cyclic, peptides which are remarkably potent.

"These peptides are easy to synthesis and modify and will accelerate our research in this field. It also highlights the growing 'team ice' collaborative network at Warwick, combining experimental and computation studies together. We are also grateful for the support from the IAS at Warwick, which allowed Dr Stevens to visit us to complete this work, showing the need to support international scientific collaborations."

Credit: 
University of Warwick

Now is the time to think about reintroducing jaguars into the US

NEW YORK (May 11, 2021) - A group of scientists say now is the time to talk about reintroducing jaguars (Panthera onca) into the U.S.

In a study published today in the journal Conservation Science and Practice, the authors provide a prospective framework for this effort and describe "righting a wrong" done to "America's Great Cat" in the Southwest more than 50 years ago. The big cats lived for hundreds of years in the central mountains of Arizona and New Mexico but were driven to local extinction by the mid-20th century, in part because of killing by government hunters.

Authors of the study include a diverse set of scientists from the Wildlife Conservation Society, Center for Landscape Conservation, Defenders of Wildlife, Wildlands Network, Pace University, Universidad Autónoma de Querétaro, Life Net Nature, and the Center for Biological Diversity.

In March, a separate study suggested that an area in central Arizona and New Mexico spanning 2 million acres (82,000 square kilometers) can provide potentially suitable habitat for 90 to 150 jaguars. This area, roughly the size of South Carolina, was not considered in the 2018 US Fish and Wildlife Service Recovery Plan for the jaguar. That plan considered only habitat south of Interstate Highway 10 (an artificial boundary considering historic jaguar records north of that) and therefore concluded there was habitat for only six jaguars in the U.S.

However, habitat destruction, transportation infrastructure, natural constrictions in the landscape, and the border wall mean that natural reestablishment of female jaguars from source populations in Mexico to this recovery region is unlikely over the next 100 years.

The authors of today's study conclude that reintroduction of jaguars should be examined as a viable alternative. The authors believe that restoring jaguars can be a net benefit to people, including culture and local economies, and nature and would represent the return of an original part of the U.S. fauna.. The study focuses on on five dimensions of the reintroduction project: conservation rationale, history, ecological context, human context and practical considerations.

"The jaguar lived in these mountains long before Americans did," said Eric Sanderson, WCS Senior Conservation Ecologist and lead author of the study. "If done collaboratively, reintroduction could enhance the economy of this region and the ecology of this incredible part of jaguar range."

The study notes some key aspects of the reintroduction effort to be discussed with relevant officials and the public in central Arizona and New Mexico, noting that:

The region is a habitat unique in all of the jaguar's range, representing a special and valuable part of jaguar's ecological diversity.

The Central Arizona and New Mexico Recovery Area (CANRA) is vast, covered with suitable vegetation, and well populated with potential prey. Given its elevation and latitude, it may provide an important climate refuge for the species in the future, though further research is required.

The majority of the land is managed for the public good, mainly (68%) by the US Forest Service, Bureau of Land Management, and National Park Service, with several large designated wilderness areas. Only 381,000 people live in this area, primarily in towns and cities. The most important economic activities there are government expenditures, accommodation and food services, outdoor recreation, health care and social assistance, and retail trade.

The mountains of central Arizona and New Mexico are part of the ancestral and reservation lands for a number of Native American Nations. Currently two Tribal nations, the White Mountain Apache and the San Carlos Apache, manage nearly 12 percent of the CANRA's land area, including wildlife and ecological systems.

Reintroduction would replace a historic member of the species assemblage of the region. U.S. government agents and private citizens hunted and poisoned the jaguar for most of the 20th century. As a result of persecution here and elsewhere, jaguars were listed under the U.S. Endangered Species Act. Today we have tools to facilitate coexistence and avoid and mitigate conflict. Reintroduction efforts, such as the Iberá Project in Argentina, have demonstrated the potential. Reintroduction could contribute to the recovery and eventual removal of the jaguar from the Endangered Species List, especially if the recent recovery plan were revised to consider this area and the possibility of reintroduction.

"This represents a turning point for this iconic wild cat, identifying a path forward for restoration of the jaguar to its historic range in the United States," said Sharon Wilcox Ph.D., Texas Representative for Defenders of Wildlife. "It should serve as the starting point for a renewed conversation among stakeholders."

"The Southwest's native wildlife evolved with jaguars," said Michael Robinson of the Center for Biological Diversity. "They have a storied and vital place in our canyons and forests, so we should plan an intelligent and humane reintroduction program."

Wildlands Network Mexico and Borderlands Program Director, Juan Carlos Bravo added: "Restoring jaguars to the northernmost portions of their historic range is an issue of importance for both the U.S: and Mexico, our paper provides an initial step for both countries to draft together a roadmap of what that major rewilding effort may look like."

Credit: 
Defenders of Wildlife

Genetics: Biosynthesis pathway of a new DNA nucleobase elucidated

DNA is composed of nucleobases represented by the letters A, T, G and C. They form the basis of the genetic code and are present in all living beings. But in a bacteriophage, another base, represented by the letter Z, exists. This exception, the only one observed to date, has long remained a mystery. Scientists from the Institut Pasteur and the CNRS, in collaboration with the CEA, have now elucidated the biosynthesis pathway of this base. This work has been published in the April 30th, 2021 issue of Science.

DNA, or deoxyribonucleic acid, is a molecule that serves as the medium for storing genetic information in all living organisms. It is a double helix characterized by alternating purine nucleobases (adenine and guanine) and pyrimidine nucleobases (cytidine and deoxycytidine). The bases of each DNA strand are located at the center of the helix and are bonded together, thereby linking the two DNA strands: adenine forms two hydrogen bonds with thymine (A-T), and guanine forms three hydrogen bonds with cytosine (G-C). This applies to all living beings, with one exception.

Cyanophage S-2L, an exception to conventional genetics

Cyanophage S-2L is a bacteriophage, in other words a virus that infects bacteria. In this phage, adenine is completely replaced by another base, 2-aminoadenine (represented by the letter Z). The latter forms three hydrogen bonds with thymine (Z-T), instead of the usual two bonds between adenine and thymine. This higher number of bonds increases the stability of the DNA at high temperatures and changes its conformation, meaning that the DNA is less well recognized by proteins and small molecules.

2-aminoadenine biosynthesis pathway elucidated

Since it was discovered in 1977, cyanophage S-2L has been the only known exception, and the biosynthesis pathway of 2-aminoadenine has remained unknown. Scientists from the Institut Pasteur and the CNRS, in collaboration with the CEA, recently elucidated this biosynthesis pathway and demonstrated its enzymatic origins. They achieved this by identifying a homolog of the known enzyme succinoadenylate synthase (PurA) in the genome of cyanophage S-2L. A phylogenetic analysis of this enzyme family revealed a link between the homolog, known as PurZ, and the PurA enzyme in archaea. This indicates that the homolog is an ancient enzyme that probably conferred an evolutionary advantage. The research was carried out using the Institut Pasteur's Crystallography Platform.

The new Z-T base pair and the discovery of the biosynthesis pathway show that new bases can be enzymatically incorporated into genetic material. This increases the number of coding bases in DNA, paving the way for the development of synthetic genetic biopolymers.

Credit: 
Institut Pasteur

Extreme weather affecting UK agriculture -- But adapting to changing climate a challenge for many farmers, study shows

Extreme weather is harming UK agriculture - but many farmers have not yet made adapting to the effects of the climate emergency a priority, a new study shows.

All farmers who took part in the research said they had experienced or witnessed issues caused by extreme weather such as heavy rain or prolonged dry spells in recent years, and expected these to intensify further.

Many were concerned about the impact of heat and drought on crop and grass growth, with knock-on impacts for yield and winter animal feed, and the implications of heavy rainfall/flooding for soil run-off and erosion and for field operations such as drilling and harvesting. For a number of farmers, however, ongoing and future changes to our weather and climate were seen as too uncertain and too long-term for them to invest significant time or money in planning for them now,

The study shows many farmers are focused on short-term profitability and business survival in a challenging economic environment, as well as concerned about other political and public pressures. Although there is a growing acceptance that the climate is changing and that there are benefits to taking action, uncertainties about the exact scale, speed and nature of change locally, make it difficult for farmers to plan ahead.

The research, published in the journal Climate Risk Management, was carried out by Dr Rebecca Wheeler and Professor Matt Lobley from the University of Exeter's Centre for Rural Policy Research, in partnership with scientists from the Centre for Ecology and Hydrology, Rothamsted Research and Lancaster University.

Researchers carried out 31 in-depth interviews, 15 with farmers and 16 with stakeholders including advisors, consultants and industry representatives.

A number of agricultural stakeholders said they were concerned too few farm businesses are taking sufficient action to increase their business resilience to extreme weather and climate change.

Some farmers "hadn't got around" to certain measures they would like to undertake, whilst others were "concentrating on the short term".

Dr Wheeler said: "Farmers have an array of challenges and uncertainties to cope with, and it is understandable they are focused on the short-term profitability and survival of their business. This seems to be preventing them from adapting to the effects of the climate emergency. It is essential the industry finds ways to build resilience, and that farm businesses are supported in planning and responding to changing weather patterns."

More positively, the research also highlighted the capacity for innovation and adaptability within the farming industry. Many farmers are building resilience within their business through actions to improve soil health, which as well as raising productivity and storing carbon, also increases the ability for grass and crops to cope with weather extremes. There is also reason for farmers to be optimistic about some of the opportunities posed by climate change, such as warmer temperatures enabling new crops and increased yields in some instances, - as long as they are able to 'weather' the challenges posed by negative effects.

As well as improving soil health, positive actions taken by farmers in the research to future-proof their business included continuous evaluation of crop/grass varieties and growing techniques, installing additional livestock housing with good ventilation, increasing rainwater storage capacity, and risk-spreading through expanding the diversity of their crops and enterprises.

Professor Lobley said: "There are many innovative and exciting activities happening on farms across the country, but much is still to be done to improve the resilience of individual farms and the industry as a whole.

"Few farmers described themselves as directly adapting to climate change but most did see themselves as taking positive steps to respond to the risks of extreme weather or to generally improve their business resilience. For a number of farmers this primarily took the form of improving soil health."

Industry representatives involved in the research welcomed such positive steps but called for greater uptake of these and other measures. The findings highlighted a need for government and agricultural stakeholders to work with farmers to help them understand the risks posed to their particular business from extreme weather and climate change. Actions to help farmers respond and adapt to these risks include improved industry collaboration, creating opportunities for farmer-to-farmer learning, and providing tailored tools and support that take into account the specificities of different farming systems.

Credit: 
University of Exeter

Social isolation has a profound and increasingly negative impact on physical functioning in older adults

Ann Arbor, May 11, 2021 - Social isolation among older adults is associated with poor health and premature mortality, but the connection between social isolation and physical functioning is poorly understood. New research generates more robust evidence about the associations between social isolation and physical functioning and how this accelerates over time, reports the American Journal of Preventive Medicine, published by Elsevier. It also highlights the importance of incorporating strategies to reduce social isolation and promote successful aging.

"Physical functioning is understood to influence the health of individuals. And social isolation is prevalent among older adults," explained lead investigator Borja del Pozo Cruz, PhD, Centre for Active and Healthy Ageing, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark. "However, the true extent of the relationship between social isolation and physical functioning was not fully understood. We needed to shed some more light on this relationship, as it plays an important role in individual aging."

As individuals age, physical functioning declines, which can result in a loss of functional independence, onset of disability, and increased mortality, with significant personal, community, and economic costs. Older adults who are socially integrated may be more likely to engage in physical activity, which would in turn elicit improvements in their physical functioning.

Social isolation is a significant problem facing the health and well-being of individuals across the life course. Individuals who are socially isolated are more likely to experience mental health problems, develop dementia, and have increased risk of premature mortality. Social isolation is particularly worrisome among older adults, with data from the United States indicating that one in four older adults is isolated or severely isolated. Given the worldwide trends in population aging, social isolation among older adults is likely to become an increasing burden in years to come.

To examine the longitudinal associations between social isolation and physical functioning, investigators used nine waves of panel data from 2011 to 2019 from the National Health and Aging Trends Study (NHATS), a large US-representative sample of adults 65 or older. This means that the results can be generalized to the US population of older adults. The study analyzed observations from 12,427 NHATS participants to measure how individual changes in social isolation were associated with individual changes in objectively assessed physical functioning. Social isolation was captured through the Social Isolation Index (SII). Physical functioning was assessed using the NHATS version of the Short Physical Performance Battery (SPPB). The analytic sample encompassed 54,860 observations, meaning that respondents were observed 4.41 times on average.

These findings add to a growing evidence base demonstrating the negative consequences of social isolation, specifically the acceleration of aging decline trajectories in physical functioning. Investigators were able to identify with a high degree of granularity how the association between social isolation and physical functioning shifts over old age and exacerbates the decline in physical functioning associated with aging. The results showed that the older individuals are, the greater the extent to which social isolation impacts their health.

A small but growing number of observational studies in the UK, Japan, and China have identified negative associations between social isolation and physical functioning in samples of older adults. The current study resonates with and complements those results. However, the robust data generated by this national rather than community-based study enable findings to be generalized to a national population.

"Physical functioning is a well-established marker of general health and it has been previously correlated with morbidity and mortality," noted Dr. del Pozo Cruz. "We demonstrate in this study that social isolation has a profound impact on the physical functioning in older adults. Mandated social contact restrictions and lockdowns due to COVID-19, coupled with more severe consequences of contagion among older adults, have likely exacerbated this trend.

Study findings suggest that public health interventions should turn their attention to the social environments in which older people are embedded, in particular for those at risk of isolation.

"Social isolation is one of the biggest challenges that societies face in the 21st century. We have to start thinking about this issue now to avoid more serious consequences down the track," added Dr. del Pozo Cruz.

Credit: 
Elsevier

How do you rate your medical care? Your answer might be affected by your insurance

May 11, 2021 - For patients seen at a urology clinic, patient satisfaction scores vary by insurance status - with higher scores for patients on Medicare and commercial insurance, but lower scores for those on Medicaid, reports a study in Urology Practice®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Our study adds to previous evidence showing patient satisfaction scores are affected by the type of insurance - not just by the quality of care provided," comments senior author Werner de Riese, MD, PhD, Chair of the Department of Urology of Texas Tech University Health Sciences Center (TTUHSC), Lubbock. "That may have important implications for physician reimbursements, which are increasingly adjusted upward or downward based on patient satisfaction ratings."

Urology clinic data show 'payor-bias' in patient ratings

The researchers analyzed satisfaction ratings made by nearly 21,000 patients seen at the TTUHSC urology clinic between 2013 and 2020. Patient satisfaction scores were compared for those with different kinds of insurance coverage.

Forty-six percent of patients were covered by commercial/private insurance, 37 percent by Medicare and nine percent by Medicaid. Five percent of patients had other government coverage; self-pay or workers' compensation patients accounted for less than two percent each.

Patient satisfaction ratings differed between groups. Medicare patients reported the highest average score, 93.03 (on a 0-to-100 scale); followed by other government coverage, 91.49; commercial insurance, 91.32; workers' compensation, 90.72; Medicaid, 89.21; and self-pay/uncompensated, 89.00.

Although the numerical range was small, the data showed several statistically significant differences between groups. The "other" government group - mainly veterans or active-duty military members covered by the Veterans Administration or Tricare - reported "generally higher" patient satisfaction levels than every other group besides Medicare.

In contrast, Medicaid and self-pay patients had the lowest satisfaction scores. "Medicaid often covers the most vulnerable and disadvantaged patients, and our results are consistent with other studies reporting that hospitals treating more Medicaid patients have lower satisfaction scores," says Dr. de Riese.

Medicare and Medicaid have introduced "fee for performance" payments, in which reimbursements to physicians and hospitals are adjusted based on quality measures - including patient satisfaction scores. Commercial insurance plans are also moving toward such "value-based" reimbursement plans. However, there are concerns patient satisfaction scores may be affected by certain non-modifiable characteristics, including insurance status.

"Data from our urology clinic illustrate a potential bias in reported patient satisfaction levels, based on their health insurance coverage," says Dr. de Riese. The researchers call for further studies to explore the underlying reasons for this "payor-specific bias," particularly among Medicaid patients. "Meanwhile," Dr. de Riese adds, "we believe reimbursement policies should be modified to account for the payor-mix of patients seen by each physician."

Click here to read "Association Between Payor-Class and Patient Satisfaction Scores in an Academic Urology Outpatient Clinic."

DOI: 10.1097/UPJ.0000000000000224

Credit: 
Wolters Kluwer Health

Space-based system can provide seismic monitoring for large earthquakes and tsunamis

image: GNSS station in the U.S. Pacific Northwest.

Image: 
Pacific Northwest Geodetic Array, Central Washington University

Researchers have developed a global earthquake monitoring system that uses the Global Navigational Satellite System (GNSS) to measure crustal deformation.

The monitoring system within seconds can rapidly assess earthquake magnitude and fault slip distribution for earthquakes of magnitude 7.0 and larger, making it a potentially valuable tool in earthquake and tsunami early warning for these damaging events, Central Washington University geophysicist Timothy Melbourne and colleagues report in the Bulletin of the Seismological Society of America.

GNSS can potentially characterize a large earthquake much more rapidly than the global seismic network, offering more time for evacuations, drop-and-cover and automatic shut-down of essential infrastructure. "The imperative for doing it quickly is really about saving lives," said Melbourne.

GNSS systems consist of Earth-orbiting satellites that send signals to receiver stations on Earth. The signals are used to determine the receivers' exact locations through time. Earthquakes move and deform the Earth's crust underneath the receivers, so changes in their locations after an earthquake can be used to monitor and characterize the ruptures.

Seismic monitoring by GNSS is a "very blunt tool," compared to seismometer-based networks capable of detecting minute seismic waves, Melbourne said.

A top-of-the-line seismometer is remarkably sensitive, he noted, able to detect seismic wave velocities as small as tens of nanometers per second.

GNSS is more coarse, only detecting displacements of centimeters or larger.

During a big earthquake, however, there is a trade-off between sensitivity and speed. Local seismic networks can be swamped with data during a large, complex event such as the 2016 magnitude 7.8 Kaikoura earthquake in New Zealand, where multiple faults are involved and waves from the initial event reverberate through the crust. To accurately determine magnitude and fault slip distribution, seismologists usually have to wait for the seismic wave data to reach distant stations before it can be accurately characterized, which involves tens of minutes of delay while the waves propagate across the planet.

The global system created by Melbourne and his colleagues is the first of its kind. It takes in raw GNSS data acquired at any Internet-connected receiver on Earth, positions these data, and then re-transmits the positioned data back to any Internet-connected device, within a second.

The researchers assessed their system over one typical week, using data from 1270 receiver stations across the world. They found that the average time it took data to travel from a receiver to the processing center at Central Washington University was about half a second--from anywhere in the world. It took an average of about one-200th of a second to convert that data into estimates of GNSS position.

This means that the GNSS global monitoring system can detect changes well before the earthquake itself is done rupturing, since it can take tens of seconds--or even minutes for the largest earthquakes--"for the fault to unzip and radiate all that energy into the planet," Melbourne said.

The speed of a global GNSS seismic monitoring system might be even more important for tsunami warnings, he noted. At the moment, an international monitoring program uses data from a global seismic network to determine an earthquake magnitude, combined with data from global tide gauges and buoys that detect a tsunami wave in the open ocean, to determine whether a tsunami advisory should be sent to the public.

The seismic network could take 15 minutes or more to determine the magnitude of an earthquake that causes a tsunami, said Melbourne, and the tidal gauges and buoys could take up to an hour to deliver data, depending on their proximity to the earthquake. GNSS receivers, on the other hand, could characterize an earthquake in tens of seconds with sufficient nearby stations.

"The real power of the GNSS for the tsunami is buying more time and greater accuracy from the get-go for the warnings that come out," Melbourne said.

GNSS receiver stations are proliferating around the world as more people use them, especially for surveying or monitoring in mining and construction. But the global GNSS monitoring system depends on open-source data, which has not expanded at the same rate. In some countries, data are sold to recover the costs of constructing and maintaining the receivers, Melbourne said, making their operators reluctant to make the data freely available.

"Part of what I do is trying to get countries in seismically active areas to open up their data sets for hazard mitigation purposes," said Melbourne.

For instance, GNSS operators in New Zealand, Ecuador, Chile and elsewhere partner with Melbourne's group, benefiting from the decade of work that the team has put into their GNSS positioning system. They send raw data from receivers in their countries to Central Washington, where Melbourne and colleagues position the data within a global reference frame and send it back within subseconds for further research and monitoring.

Credit: 
Seismological Society of America

Shared medical appointments help patients with prediabetes

Researchers from the Cleveland Clinic and Takeda Pharmaceutical Company conducted a study to evaluate the effectiveness of shared medical appointments for people with pre-diabetes compared with a group of patients receiving usual care. Shared medical appointments are typically delivered in a medical clinic by physicians and other health care providers. Within the context of this study, shared medical appointments consisted of patients consulting with their doctors one-on-one and then joining a group of similar patients to set goals and review lab results with the same family physician and a diabetes educator. Researchers also assessed the impact of attending a shared medical appointment versus care-as-usual on chronic conditions such as high blood sugar, cholesterol and blood pressure.

Over 24 months, patients who took part in shared medical appointments lost more weight than those who received usual care. By the conclusion of the study period, patients who attended shared medical appointments showed better outcomes in managing the aforementioned chronic conditions than those patients who received usual care.

Researchers concluded that shared medical appointments may provide an effective model of treatment for patients with pre-diabetes. As the diabetic epidemic continues, the authors call for more research using shared medical appointments to manage prediabetes in health care systems.

Credit: 
American Academy of Family Physicians

Rules of the road: the navigational 'strategies' of bacteria in motion

image: By observing 5 different species of bacteria moving through a variety of microfluidic channels, the researchers discovered that bacteria navigated through the spaces not based on their own sizes or proportions, as the researchers had imagined, but instead depending on the kinds of spaces they were navigating through.

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McGill University

Bacteria that move around live on the edge. All the time. Their success, be it in finding nutrients, fending off predators or multiplying depends on how efficiently they navigate through their confining microscopic habitats. Whether these habitats are in animal or plant tissues, in waste, or in other materials. In a recent paper published in PNAS, a team of researchers led by McGill University, has described a number of factors affecting how five, very different, species of bacteria search and navigate through varied microfluidic environments which pose various decisional challenges. This increased understanding of the bacterial space searching and navigational 'strategies' has implications for everything from diagnosing infectious diseases and maintaining human health, to the development of devices for everything from genomics to bio computation, as well as for a wide range of agricultural, industrial, and environmental activities.

The researchers filmed the movements of five species of bacteria navigating through a range of microfluidic settings - from fairly open spaces (plazas) to complicated meandering channels. This allowed them to better understand the factors involved in the navigational 'strategies' of bacteria as they search for available space.

See sample video

Q & A with senior author Professor Dan Nicolau
from McGill University's Department of Bioengineering

Q- What 'strategies' do bacteria use to navigate through space?

A - We found, by observing bacterial movement through microfluidic channels of different shapes and sizes, that bacteria use vastly different 'algorithms' for searching through space than we had expected. These algorithms are not, as we thought, governed by the complexity of bacterial architecture - but rather by the spaces the bacteria are investigating. We found that a lot depends on the shape and the size of the channel that the bacteria are navigating. In general, bacteria don't waste time on U-turns, unless they have no choice due to the tightness of the channels.

Although the natural "movement technology" used by bacteria are very different from species to species, their space searching strategies are determined by their geometrical ratios, for instance cell width vs. length of flagella (the whip-like structures protruding from cell body that some bacteria use for locomotion).

Despite their differences, all the species we looked at were able to successfully negotiate through tight (relative to their sizes) paths, and certainly through larger ones. But in medium-sized meandering channels, bacteria cannot rely on the constricting walls to guide them, nor can they move totally freely. As a consequence, they become 'confused' about what search method they should use and they are trapped, regardless of what algorithms they are programmed to use.

Q - How can this information be used?

A - In terms of diseases, whether in humans, animals, or plants, this information will help us better understand better how bacteria colonise confining spaces. This is useful for various reasons, such as focusing attention on how certain animal species may be more exposed to infections by certain bacterial species, due to their particular spacial navigation and exploration strategies.

For bacterial genomics, which are important in the understanding, treatment and prevention of the spread of infectious diseases, understanding the 'algorithms' used by different species of bacteria will make it easier to design geometries that trap only a single species from samples collected in water, human fluids, etc. that may contain a whole range of bacterial populations.

For bio computation - that is, building computers powered by bacteria - it is crucial to know what algorithms the bacteria use for motion in order to build computers that do not make errors.

Credit: 
McGill University

Understanding SARS-COV-2 proteins is key to improve therapeutic options for COVID-19

COVID-19 has had a significant impact since the pandemic was declared by WHO in 2020, with over 3 million deaths and counting, Researchers and medical teams have been hard at work at developing strategies to control the spread of the infection, caused by SARS-COV-2 virus and treat affected patients. Of special interest to the global population is the developments of vaccines to boost human immunity against SARS-COV-2, which are based on our understanding of how the viral proteins work during the infection in host cells. Two vaccines, namely the Pfizer/BioINtech and Oxford/AZ vaccine rely on the use of delivering the gene that encodes the viral spike protein either as an mRNA or through an adenovirus vector to promote the production of relevant antibodies. The use of monoclonal antibodies has also been approved by the US Food and Drug Administration.

It is very clear that viral proteins provide interesting and potentially effective targets for neutralizing viruses, and SARS-COV-2 is no exception. A recent review published in Current Molecular Medicine presents a summary of SARS-COV-2 proteins. The review, authored by M. E. A. Mohammed (King Khalid University, Saudi Arabia) presents tabular information about 3 major types of SARS-COV-2 proteins: functional proteins (which represent enzymes responsible for viral replication, receptor binding, viral invasion and virion assembly and release), structural proteins (which are associated with the viral protein coat), and accessory proteins (which help in viral replication and virus-host interactions). In addition to informative tables, the review also provides current information about individual proteins in detail in terms of structure and molecular function.

The author points out that SARS-COV-2 proteome consists of proteins that have an increased number of amino acids (nsp3 and spike protein), deleted proteins (orf3b and orf9b) and inserted proteins (orf10). The list of proteins has been compared with variants in SARS-COV and another bat coronavirus species (RATG13). A number of structural and nonstructural proteins of SARS-COV-2 are conserved among the coronavirus species. The list of proteins provides a good starting point for researchers to search for possible pharmaceutical targets for combatting SARS-COV-2 infections.

Credit: 
Bentham Science Publishers

Gene editing expands to new types of immune cells

image: Alex Marson (left), Nevan Krogan (right), and their team fine-tuned CRISPR-Cas9 genome editing to work on human immune cells called monocytes.

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Photo: Michael Short/Gladstone Institutes

In the decade since the advent of CRISPR-Cas9 gene editing, researchers have used the technology to delete or change genes in a growing number of cell types. Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have added human monocytes--white blood cells that play key roles in the immune system--to that list.

The team has adapted CRISPR-Cas9 for use in monocytes and shown the potential utility of the technology for understanding how the human immune system fights viruses and microbes. Their results were published online today in the journal Cell Reports.

"These experiments set the stage for many more studies on the interactions between major infectious diseases and human immune cells," says senior author Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and associate professor of medicine at UCSF.

"This technology opens doors for identifying the human genes most important to the function of monocytes and for coming up with new therapeutic strategies against a range of pathogens," adds co-senior author Nevan Krogan, PhD, senior investigator at Gladstone and director of the Quantitative Biosciences Institute at UCSF.

From One Immune Cell to Another

Monocytes are immune cells with a broad range of roles in defending the human body from pathogens. As part of their normal function, monocytes can give rise to two other immune cell types: macrophages, which engulf and destroy foreign material in the body, and dendritic cells, which help recognize pathogens and trigger more specific immune responses.

Marson's team has previously studied T cells, a different class of immune cell, using CRISPR-Cas9 technology to selectively remove genes from the cells and observe the consequences. Their results have helped point toward targets for new immune therapies that make T cells more effective at fighting disease.

Monocytes, however, are notoriously hard to study in the lab. Few of the cells circulate in the blood and they behave differently in a petri dish than they would inside the body. So, applying CRISPR-Cas9 to monocytes required tweaking the standard protocols. The team had to develop an approach that would not only alter the genes inside monocytes, but ensure that those edited cells were still functional.

"Editing monocytes was challenging, but we felt it was very important to replicate the success we had obtained with T cells in other immune cells," says Joseph Hiatt, the study's first author and a graduate student in the Marson and Krogan labs.

A Way to Study Infections

The group showed that the monocytes edited with their CRISPR-based approach could still give rise to both macrophages and dendritic cells. To confirm whether these new edited cells behaved normally, the researchers infected cells grown in the lab with the microbe that causes tuberculosis. Macrophages originating from edited monocytes, they found, were still capable of engulfing the pathogen.

The researchers next showed that using CRISPR-Cas9 to remove the gene SAMHD1 from monocytes--and therefore the resulting macrophages--boosted more than fifty-fold the infection of cells by HIV. While SAMHD1 was already known to protect human cells from HIV, the experiment confirmed the success of their gene-editing approach in monocytes and its promise for studying diseases.

Krogan's lab has spent recent years cataloging human proteins that viruses use to infect cells and propagate. His research has included HIV, tuberculosis, Ebola virus, and Dengue virus--viruses known to target macrophages and dendritic cells. The new ability to edit genes in these cells will help his team validate their findings and identify vulnerabilities that may help combat these diseases in the future. It could also point toward targets for drugs that help boost the ability of monocytes to fight infections, or block viruses from hijacking monocytes in the first place.

"Now that we're confident we can edit monocytes successfully, our approach will allow us to study these cells in depth, and understand their roles in infectious diseases," says Devin Cavero, co-first author of the study and former UCSF research associate.

Credit: 
Gladstone Institutes