Culture

Harmful protein waste in the muscle

image: Heart of a healthy (left) and a diseased mouse (cross sections). Connective tissue inclusions (right, red) make the diseased heart less efficient.

Image: 
© Kenichi Kimura/UKB

An international team of researchers led by the University of Bonn (Germany) has identified the cause of a rare, severe muscle disease. According to these findings, a single spontaneously occurring mutation results in the muscle cells no longer being able to correctly break down defective proteins. As a result, the cells perish. The condition causes severe heart failure in children, accompanied by skeletal and respiratory muscle damage. Those affected rarely live beyond the age of 20. The study also highlights experimental approaches for potential treatment. Whether this hope will be fulfilled, however, will only become clear in a few years. The results are published in the journal Nature Communications.

Anyone who has ever snapped a spoke on their bike or broken down with their car knows that mechanical stresses sooner or later result in damage that needs to be repaired. This also applies to the human musculature. "With each movement, structural proteins are damaged and have to be replaced," explains adjunct professor Dr. Michael Hesse from the Institute of Physiology at the University of Bonn, who led the study together with his colleague Prof. Dr. Bernd Fleischmann.

The defective molecules are normally broken down in the cell and their components are then recycled. An important role in this complex process is played by a protein called BAG3. The results of the new study show how important this is: The researchers were able to demonstrate that a single change in the genetic blueprint of BAG3 results in a fatal disease.

"The mutation causes BAG3 to form insoluble complexes with partner proteins that grow larger and larger," Hesse says. This brings the repair processes to a standstill - the muscles become less and less efficient. Moreover, toxic levels of proteins accumulate over time, eventually resulting in the death of the muscle cell. "The consequences are usually first seen in the heart," Hesse says. "There, muscle is successively replaced by scar tissue. This causes the heart's elasticity to decrease until it can barely pump blood."

Affected individuals therefore usually require a heart transplant in childhood. Even this measure only provides temporary relief, as the disease also affects the skeletal and respiratory muscles. As a result, sufferers often die at a young age.

Very rare condition, therefore little research

The lethal mutation can arise spontaneously during embryo development. Fortunately, this is a very rare occurrence: There are probably only a few hundred affected children worldwide. However, due to its rarity, the disease has received little research attention to date. "Our study now takes us a great deal further," stresses Bernd Fleischmann.

This is because the researchers have succeeded for the first time in replicating the disease in mice and using the new animal model to identify its causes. This allows it to be researched better than before - also with regard to possible therapies. Maybe the effect of the mutation can at least be reduced. Humans have two versions of each gene, one from the mother and the other from the father. This means that even if one version of BAG3 mutates during embryo development, there is still a second gene that is intact.

Unfortunately, however, the defective BAG3 also clumps with its intact siblings. The mutation in one of the genes is therefore sufficient to stop the breakdown of the defective muscle proteins. However, if the mutated version could be eliminated, the repair should work again. It would also prevent the massive accumulation of proteins in the cell that eventually results in its death.

There are indeed methods to specifically inhibit the activity of individual genes. "We used one of them to treat the sick mice," explains Kathrin Graf-Riesen of the Institute of Physiology, who was responsible for most of the experiments along with Dr. Kenichi Kimura and her colleague Dr. Astrid Ooms. The animals treated in this way then showed significantly fewer symptoms. Whether this approach can be transferred to humans, however, remains the subject of further research.

Credit: 
University of Bonn

Communication technology, study of collective behavior must be 'crisis discipline'

Our ability to confront global crises, from pandemics to climate change, depends on how we interact and share information.

Social media and other forms of communication technology restructure these interactions in ways that have consequences. Unfortunately, we have little insight into whether these changes will bring about a healthy, sustainable and equitable world. As a result, researchers now say that the study of collective behavior must rise to a "crisis discipline," just like medicine, conservation and climate science have done, according to a new paper published June 14 in the Proceedings of the National Academy of Sciences.

"We have built and adopted technology that alters behavior at global scales without a theory of what will happen or a coherent strategy for reducing harm," said Joseph B. Bak-Coleman, the lead author and a post-doctoral researcher at the University of Washington's Center for an Informed Public.

Social media and other technological developments have radically reshaped the way that information flows on a global scale. These platforms are driven to maximize engagement and profitability, not to ensure sustainability or accurate information -- and the vulnerability of these systems to misinformation and disinformation poses a dire threat to health, peace, global climate and more.

No one, not even the platform creators themselves, have much understanding of how their design decisions impact human collective behavior, the authors argue.

"We urgently need to understand this and move forward with focus on developing social systems that promote well-being instead of creating shareholder value by commandeering our collective attention," said co-author Carl T. Bergstrom, a UW professor of biology and faculty at the Center for an Informed Public.

Collective behavior and other complex systems are fragile. "When perturbed, complex systems tend to exhibit finite resilience followed by catastrophic, sudden, and often irreversible changes," the authors write.

While there are studies and disciplines that focus on complex systems in the natural world, "we have a far poorer understanding of the functional consequences of recent large-scale changes to human collective behavior and decision making," the authors write.

Averting catastrophe in the medium term (e.g., coronavirus) and long term (e.g., climate change, food security) will require rapid and effective collective behavioral responses -- yet it remains unknown whether human social dynamics will yield such responses.

"We have seen individual studies about how climate-change disinformation gets over-represented even in the mainstream media, and studies that show that in digital media that problem only gets worse," said co-author Jennifer Jacquet, an associate professor of environmental studies at New York University.

Lacking a developed framework, tech companies have also fumbled their way through the ongoing coronavirus pandemic, unable to stem the "infodemic" of misinformation that impedes public acceptance of pandemic control measures such as wearing masks and widespread testing for the virus.

The situation parallels challenges faced in conservation biology and climate science, where insufficiently regulated industries optimize profits while undermining the stability of ecological and Earth systems.

"If we have a decade or so to act on climate change, we have far less time to sort out our social systems," Bak-Coleman said.

Historically collective behavior has best been understood as when animals or people exhibit coordinated action without an obvious leader. This includes how fish school to evade predators or when a crowd spontaneously breaks into applause or becomes silent.

That thinking has evolved over the past decade, the authors write, from a phenomena to a contemporary view of collective action as framework that reveals how interaction between individuals gives rise to collective action.

Credit: 
University of Washington

A frozen leap forward

(Santa Barbara, Calif.) -- Scientists at UC Santa Barbara, University of Southern California (USC), and the biotechnology company Regenerative Patch Technologies LLC (RPT) have reported new methodology for preservation of RPT's stem cell-based therapy for age-related macular degeneration (AMD).

The new research, recently published in Scientific Reports, optimizes the conditions to cryopreserve, or freeze, an implant consisting of a single layer of ocular cells generated from human embryonic stem cells supported by a flexible scaffold about 3x6 mm in size. This implant is currently in clinical trial for the treatment of AMD, the leading cause of blindness in aging populations. The results demonstrate that the implant can be frozen, stored for long periods and distributed in frozen form to clinical sites where it is designed to be thawed and immediately implanted into the eyes of patients with macular degeneration. The capacity to cryopreserve this and other cell-based therapeutics will extend shelf life and enable on-demand distribution to distant clinical sites, increasing the number of patients able to benefit from such treatments.

The report published by lead author Britney Pennington and colleagues achieves a milestone that brings ocular implants one step closer to the clinic. "This is the first published report that demonstrates high viability and function of adherent ocular cells following cryopreservation, even after long-term frozen storage," said Pennington, head of process development at RPT and assistant project scientist at UC Santa Barbara.

The study demonstrates that cryopreserved implants are comparable to their non-cryopreserved counterparts in appearance, gene expression and cellular function. "It's a major advance in the development of cell therapies using a sheet of cells, or a monolayer of cells, because you can freeze them as the final product and ship them all over the world," said UCSB professor and senior author Dennis O. Clegg,

The implant used in the study consists of clinical-grade retinal pigmented epithelial (RPE) cells derived from human embryonic stem cells by collaborators at cancer hospital City of Hope, and a synthetic scaffold made of ultrathin parylene designed by engineers at California Institute of Technology and manufactured by LEAP Biomed Innovators. The resulting implant consists of cells attached to the scaffold, which permits the targeted delivery of therapeutic cells to the diseased region within the eye. A non-cryopreserved formulation of this cellular therapy is being employed in an ongoing Phase I/IIa clinical trial sponsored by RPT. The cryopreserved formulation enabled by the work of Pennington and colleagues will facilitate anticipated Phase IIb and Phase III clinical trials as well as ultimate commercialization and clinical application of the product.

Credit: 
University of California - Santa Barbara

Introducing play to higher education reduces stress and forms deeper connection material

A new study found higher education students are more engaged and motivated when they are taught using playful pedagogy rather than the traditional lecture-based method. The study was conducted by University of Colorado Denver counseling researcher Lisa Forbes and was published in the Journal of Teaching and Learning.

While many educators in higher education believe play is a method that is solely used for elementary education, Forbes argues that play is important in post-secondary education to enhance student learning outcomes.

Throughout the spring 2020 semester, Forbes observed students who were enrolled in three of her courses between the ages of 23-43. To introduce playful pedagogy, Forbes included games and play, not always tied to the content of that day's lesson, at the start of each class. She then provided many opportunities for role-play to practice counseling skills, and designed competitions within class activities.

During the study, students mentioned they saw more opportunities for growth while learning in a highly interactive environment. Students also described that the hands-on nature of learning through play established a means for skill acquisition, and they were able to retain the content more effectively.

"As we grow older, we're conditioned to believe that play is trivial, childish, and a waste of time," said Forbes. "This social script about play leads to it being excluded from higher education. A more interactive learning approach leads to a deeper and more rigorous connection to the material."

To maintain what Forbes described as "rigor" within higher education, the most common approach tends to be lecture-based learning. However, according to Forbes, this mode of education is counter to the very outcomes educators set out to achieve.

The results of the study suggest there is a unique and powerful classroom experience when play is valued and used in the learning process. According to Forbes, students who participated in this study also indicated that play increased positive emotions and connections with other students and the professor in the course.

"I also saw that when I introduced play, it helped students let their guard down and allowed them to reduce their stress, fear, or anxiety," said Forbes. "Play even motivated students to be vulnerably engaged, take risks, and feel more connected to the content."

Play is underutilized and devalued in higher education, according to Forbes. She suggests educators reevaluate their understanding of using play in graduate courses. Playful pedagogy creates an interactive and warm learning environment, resulting in greater understanding of the material. This method is also more aligned with the humanistic missions and values of universities and programs.

Credit: 
University of Colorado Denver

Telemedicine program improves access to sleep care for rural veterans

DARIEN, IL - More veterans are receiving important sleep care, especially those living in rural areas where access to sleep medicine specialists can be difficult. The Veterans Health Administration's TeleSleep Program launched telehealth services in 2017 to support the testing, diagnosis, and treatment of obstructive sleep apnea and other sleep disorders. More than one million veterans who received care from VHA in 2020 have sleep apnea.

"The implementation of these services has been very successful," said Dr. Kathleen Sarmiento, program lead for the Office of Rural Health TeleSleep Program and national lead for VHA TeleSleep. Sarmiento is also the director of a new regional VA TeleSleep program covering northern California, Nevada, and Hawai'i Pacific Islands, based out of the San Francisco VA Health Care System, modeled off best practices from the ORH program but focused on reaching both urban and rural veterans. She is an associate professor of medicine at the University of California, San Francisco. "The reach of this network is impressive, with 8% of VA's health care systems (hubs within this network) providing care to 18% of all rural Veterans seen for sleep care nationally."

A new study from VHA's Office of Rural Health (ORH) TeleSleep Program evaluated the expansion of telemedicine, home sleep apnea testing and remote sleep apnea management for veterans at 12 hubs and 63 spokes across the country. From 2017 to 2020, the number of rural veterans seen for sleep-related disorders at TeleSleep sites tripled and the number of encounters for sleep-related disorders more than doubled. In 2020, 72% of rural veterans at the TeleSleep hubs or spokes had at least one virtual sleep visit. This was significantly higher than non-TeleSleep VA sites where only 64% of rural Veterans had virtual visits.

"These results are very impactful as they demonstrate how funding a network of programs who share the same mission and purpose can result in significant return on investment for an organization like VA. This program was one of the first enterprise-wide initiatives funded through VA's Office of Rural Health and has also been one of the most successful in terms of reach," said Sarmiento.

Credit: 
American Academy of Sleep Medicine

New health benefits of red seaweeds unveiled

image: Red seaweeds contain sugars, such as agarotriose (AgaDP3) and 3,6-anhydro-L-galactose (AHP), that stimulate the growth of prebiotic bacteria and cause apoptosis in human colon cancer cells.

Image: 
Eun Ju Yun

Red seaweeds have been prevalent in the diets of Asian communities for thousands of years. In a new study, published in Marine Drugs, researchers have shown how these algae confer health benefits.

"In the past, people have wondered why the number of colon cancer patients in Japan is the lowest in the world," said Yong-Su Jin (CABBI/BSD/MME), a professor of food microbiology. "Many assumed that it was due to some aspect of the Japanese diet or lifestyle. We wanted to ask whether their seaweed diet was connected to the lower frequency of colon cancer."

Although several studies have shown that Asians who eat seaweed regularly have lower risk of colon, colorectal, and breast cancer, it was unclear which component was responsible for the anti-cancer effects.

In the study, the researchers broke down the structure of different types of red seaweed using enzymes and tested the sugars that were produced to see which one of them caused health benefits. Among the six different sugars produced, agarotriose and 3,6-anhydro-L-galactose, or AHG, showed the most promise.

"After we produced these sugars, we tested their prebiotic activity using the bacteria Bifidobacterium longum ssp. infantis," said Eun Ju Yun, a former postdoctoral researcher at the Carl R. Woese Institute for Genomic Biology. B. infantis is a probiotic bacterium; it colonizes the gut of infants and provides health benefits. Among the seaweed-derived sugars, the bacteria could only consume agarotriose, indicating that it works as a prebiotic i.e., it improves the growth of probiotic bacteria.

"We also tested another strain, B. kashiwanohense, and found that it also consumed agarotriose," Jin said. "These results show us that when we eat red seaweed, it gets broken down in the gut and releases these sugars which serve as food for the probiotic bacteria. It could help explain why Japanese populations are healthier compared to others."

The researchers also tested the sugars to see if they had any anti-cancer activity. "We found that AHG specifically inhibits the growth of human colon cancer cells and does not affect the growth of normal cells," Yun said. The anti-cancer activity of AHG is due to its ability to trigger apoptosis or cell death.

"There is a lot of information on how red seaweeds are degraded by microorganisms in the ocean and in the human body," said Kyoung Heon Kim, a professor of biotechnology and the co-advisor on the paper. "Our work explains why red seaweeds are beneficial by providing the molecular mechanism. We will continue studying their function in animal models and hopefully we will be able to use them as a therapeutic agent in the future."

Credit: 
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Reference genome comparison finds exome variant discrepancies in 206 genes

HOUSTON - (June 14, 2021) - In the two decades since the Human Genome Project mapped the entire human genome, improvements in technology have helped in developing updated reference genomes used for sequencing. But while the GRCh38 (hg38) human reference genome was released more than seven years ago, the older GRCh37 (hg19) reference remains widely used by most research and clinical laboratories. In a new study published in the American Journal of Human Genetics, researchers at the Human Genome Sequencing Center at Baylor College of Medicine identify genetic variant discrepancies between the two references, creating guidance for laboratories to take advantage of an improved human reference genome.

"There's a big push to update genomic sequencing resources to use the hg38 reference because the belief is that hg38 is a significant improvement over hg19," said Moez Dawood, co-first author of the study and student in the Medical Scientist Training Program at Baylor. "We wanted to identify the differences in sequencing readouts between the two references for labs that are still using hg19."

The Baylor researchers analyzed exome sequencing samples from more than 1,500 participants in the Baylor-Hopkins Center for Mendelian Genomics program. They found 206 genes with discordant variants between hg19 and hg38, including eight genes implicated in Mendelian diseases and 53 associated with common disease phenotypes. They found 73% of the discordant variants were clustered within sections of the genome with known assembly problems that the researchers called DISCordant Reference Patches (DISCREPs).

"This study isn't a theoretical comparison of the two references; we looked at exome data from study participants and examined the impact of using the updated reference on Mendelian genes and pathogenic variants," said Dr. Aniko Sabo, a senior author of the study and assistant professor at the Human Genome Sequencing Center. "We wanted to provide the list of 206 genes enriched with discordant variants and bring this issue to the attention of the labs working on these genes."

"For variant interpretation in the 206 genes enriched for discordant variants, reference assembly differences should be accounted for in the analysis, especially when lifting over variant coordinates from one reference to the other," said Dr. He Li, co-first author of the study and a postdoctoral associate at Baylor at the time of research.

Transitioning from using the hg19 reference to the hg38 reference takes significant time and resources. Through this large-scale study of sequencing data, the researchers aim to ease the burden on labs considering the transition. The study quantifies the benefits and drawbacks of the new reference and validates its utility in a lab setting.

"It's one thing to make a better reference. It's quite another to integrate it into useful practice," said Dr. Richard Gibbs, senior author of the study, director of the Human Genome Sequencing Center and Wofford Cain Chair and Professor of Molecular and Human Genetics at Baylor. "Some labs have been hesitant to use the new reference, but this study provides reassurance and guidance for those who are considering moving over."

Credit: 
Baylor College of Medicine

Understanding the cause of joint and tendon dysfunction in osteogenesis imperfecta

HOUSTON - (June 14, 2021) - Osteogenesis imperfecta (OI) is the most common genetic form of brittle bone disease and results in defects of both bone and connective tissue. OI patients can have significant problems with mobility due to joint dysfunction due in part to tendinopathy. In a new study published in the journal Proceedings of the National Academy of Sciences, researchers at Baylor College of Medicine identify a protein signaling mechanism driving this dysfunction and find that inhibiting this signaling pathway can prevent onset of tendinopathy problems in mouse models.

The researchers studied mouse models of OI in which the Fkpb10 gene was deleted in tendons and ligaments. The mice developed contracture, a condition in which the tendons harden, leading to joint rigidity and limited motion. As a result of the Fkpb10 gene deletion, researchers also observed inflammation in the joints and localized formation of cartilage pieces in the tendon, both symptoms of chronic tendinopathy. These symptoms coincided with the increased expression of a gene that impacts cell differentiation.

"We discovered an important signaling protein called Hedgehog, which is key in controlling the formation on cartilage, had been activated in the joints," said Dr. Brendan Lee, corresponding author of the study and Robert and Janice McNair Endowed Chair in Molecular and Human Genetics and professor and chair of the Department of Molecular and Human Genetics at Baylor.

The team, led by Lee and first author and postdoctoral associate in the Lee Lab, Dr. Joohyun Lim, wanted to see if genetic and drug inhibition of the Hedgehog signaling pathway could prevent the onset of symptoms of tendinopathy.

"By giving an FDA-approved Hedgehog signaling inhibitor, we delayed contracture and tendon degeneration and normalized joint function," said Lee, director of the Center for Skeletal Medicine and Biology at Baylor and co-director of the Rolanette and Berdon Lawrence Bone Disease Program of Texas. "We believe this could be a model for treating tendinopathy, not only in OI patients, but perhaps also in the general population."

In the future, the researchers will also work to determine if targeting inflammatory pathways as well as Hedgehog signaling can further prevent tendinopathy.

Credit: 
Baylor College of Medicine

Understanding the impact of patient empowerment and remote management in rheumatoid arthritis

The World Health Organization describes empowerment as a process in which people can take control and make informed decisions about their life and health. Empowerment is important for people with RA since most care is provided by patients themselves.

Andersson and colleagues studied levels of empowerment and associated variables in people with RA, and investigated longitudinal clinical data in those with low and high levels of empowerment. The study involved 2837 people with RA from the BARFOT (Better Anti-Rheumatic PharmacO Therapy) cohort. Everyone was assessed according to a structured protocol at inclusion and after 3, 6, 12, 24, 60, 96, and 180 months. At each follow-up disease activity, function, and pain were assessed. In 2017, a postal survey was sent with questions about disease characteristics, lifestyle habits and the Swedish Rheumatic Disease Empowerment Scale (SWE-RES-23). The 844 patients who answered the SWE-RES-23 made up the study cohort. Differences in empowerment between groups were analysed.

Regarding lifestyle habits, there were no differences between the groups in smoking habits, diet, or drinking. Moderate physical activity for at least 150 minutes per week was reported by 27% in the lowest empowerment group versus 41% in the highest empowerment group - and vigorous physical activity of at least 60 minutes per week was reported by 22% versus 37%, respectively.

In the regression analysis, several factors were associated with low empowerment:1)being a woman; 2)pain-related factors such as higher tender joint count; 3)worse patient global assessment fatigue; 4)function, and5)quality of life. Over time, the group with low empowerment reported worse pain and function at all timepoints, worse disease activity atYear2 and 8, and a worse inflammation at 15 years follow-up compared with the high empowerment group.

An important component in effective self-management may be the use of remote management technologies. Remote management of RA using patient self-assessment of disease and patient-reported outcomes has the potential to inform timely clinical decisions on disease management, reduce burden on busy rheumatology services and promote effective self-management. In a second presentation from the 2021 EULAR congress, Ndosi and colleagues report on a study to determine the agreement between remote treatment decisions based on self-assessment questionnaires assessed blindly by a health professional, and treatment decisions based on routine outpatient monitoring appointments.

Enrolled patients continued with their usual care and clinic monitoring. In addition, they completed at home, self-assessment questionnaires at monthly intervals, including: two self-reported components which are collected as part of routine clinical practice (joint stiffness and flare), visual analogue scales for pain, global health and fatigue; and function and self-efficacy scales. Remote treatment decisions were made by an independent healthcare professional, based on the self-assessment questionnaires from the patient and information collected in the study. In this analysis, the independent blinded clinician did not have the same information as the routine hospital visit clinician (blood results and joints assessment).

The remote decisions were matched with the hospital visit decisions (within 2 weeks) and the measure of agreement between the two raters was evaluated.

A total of 72 RA patients were recruited, and there were 57 matched decisions between the independent healthcare professional and the outpatient clinician. The outpatient clinician made 7 changes to biologic and 18 non-biologic therapy changes, while the remote healthcare professional made 1 change to biologic and 17 changes to a non-biologic DMARD, including bringing in for review. The self-assessment questionnaires reported 34 RA flares of which 21 had resolved. In the matched decisions, there was only one adverse event that required treatment discontinuation, identified by both the remote and the outpatient treatment.

The authors conclude that remote RA monitoring using patient self-assessment and outcome measures is feasible with fair agreement on treatment decisions. Further work is required to understand the importance of adding blood test monitoring to remote decision making.

Credit: 
European Alliance of Associations for Rheumatology (EULAR)

Study links COVID-19 public health efforts to dramatic drop in COPD hospitalizations

video: Robert Reed, M.D., describes the drop in COPD hospitalizations during COVID-19 and how public health measures such as masking may have played a role, summarizing research from the University of Maryland School of Medicine.

Image: 
University of Maryland School of Medicine

BALTIMORE (June 14, 2021) - Researchers at the University of Maryland School of Medicine (UMSOM) analyzed data at the 13-hospital University of Maryland Medical System (UMMS) and found public health measures designed to reduce the spread of the COVID-19 virus may have fostered a substantial side benefit: Hospital admissions for chronic obstructive pulmonary disease (COPD) were reduced by 53 percent, according to a new study published in The American Journal of Medicine. This is likely due to a drop in circulating seasonal respiratory viruses such as influenza.

Hospitalizations for COPD, a group of lung diseases that make it hard to breathe and get worse over time, are commonly driven by flare-ups where symptoms are triggered by such factors as tobacco smoke, air pollution and respiratory infections. Seasonal respiratory viruses, including those that cause the common cold or influenza, trigger nearly half of those flare-ups.

In the wake of a marked drop in COPD admissions during the pandemic, the researchers theorized that COVID-19 behavior changes - a mix of stay-at-home orders, social distancing, masking mandates and strict limitations on large gatherings - not only protected against COVID-19, but they may have also reduced exposure to other respiratory infections.

Conversely, they worry that the return to normal behavior may lead to more COPD flare-ups.

"Our study shows there's a silver lining to the behavior changes beyond protecting against COVID-19," said senior author Robert M. Reed, MD, UMSOM Professor of Medicine and pulmonologist at the University of Maryland Medical Center (UMMC). "If we completely eliminate masks and distancing during cold and flu season, we'll allow all those viruses that have been effectively suppressed to come raging back. There could be a lot of illness."

Prior to the COVID-19 pandemic, COPD was the fourth-leading cause of death worldwide and a leading cause of hospital admissions in the United States. The pandemic has led to significant changes in health care delivery, including reduced admissions for COPD and other non-COVID illnesses, some of which may have stemmed from patients' fear of contracting COVID in various hospital settings, as well as a shift toward telemedicine and outpatient COPD management during the pandemic.

To understand what may have occurred to reduce COPD admissions, the researchers compared weekly hospital admissions for COPD in the pre-COVID-19 years of 2018 and 2019, with admissions after the COVID-19 public health measures were instituted. At UMMS, those measures were implemented before April 1, 2020, so the investigators chose the same five-month period in each year for their comparison, April 1 to Sept. 30.

Co-lead author Jennifer Y. So, MD, UMSOM Assistant Professor of Medicine and COPD specialist at UMMC, said electronic medical records from multiple hospitals across a range of communities in the UMMS database facilitated a granular evaluation of changes over time. "We assessed a variety of possible causes that could affect COPD admissions including the presence of multiple diseases or medical conditions and the frequency of COPD exacerbations."

The database findings were correlated with data on respiratory viral trends from the U.S. Centers for Disease Control and Prevention for the period of Jan. 1, 2018, through Oct. 1, 2020.

"We found a 53 percent drop in COPD admissions throughout UMMS during COVID-19. That is substantial, but equally significant, the drop in weekly COPD admissions was 36 percent lower than the declines seen in other serious medical conditions, including congestive heart failure, diabetes and heart attack," said Dr. So.

As more and more people are vaccinated against COVID-19 and many of the public health measures of the past year are relaxed, the researchers warn that a full return to normal may again expose COPD patients to the familiar seasonal triggers.

"Our study did not assess which public health components worked to tame seasonal respiratory viruses, but a simple thing like wearing a mask while riding on public transit or working from home when you're sick with a cold could go a long way to reduce virus exposure," said Dr. Reed.

Dr. So, who is from South Korea, said it is a cultural norm to wear masks during the winter in her native country. "The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease," she said.

"This is a compelling study that raises some important public health questions about protecting our most vulnerable patient populations after we are finished with the COVID-19 pandemic. I certainly think it warrants a fuller discussion," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, University Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor.

Credit: 
University of Maryland Medical Center

As climates change, prepare for more mosquitoes in winter, new study shows

In many parts of the world, mosquitoes are a common summertime nuisance.

But in places on the front lines of climate change, these disease-spreading insects may one day be a year-round problem, according to new research from the University of Florida.

"In tropical regions, mosquitoes are active all year, but that isn't the case for the rest of the world. Outside of the tropics, winter temperatures cause mosquitoes to go into a kind of hibernation called diapause. We call these mosquitoes 'cold bounded' because their activity is limited by these lower temperatures," said Brett Scheffers, senior author of the study and an assistant professor in the UF/IFAS wildlife ecology and conservation department.

"However, with climate change, we expect summers to get longer and winters to become shorter and warmer. What will that mean for those cold bounded mosquitoes? How will they respond?" Scheffers said.

To help answer those questions, the study's authors conducted experiments with mosquitoes collected in and around Gainesville, a North Central Florida city on the dividing line between subtropical and temperate climates. Their study is published in the journal "Ecology."

The researchers compared how mosquitoes collected during different parts of the year responded to changes in temperature.

"We found that the mosquitoes in our study are what we call 'plastic,' meaning that, like a rubber band, the range of temperatures they can tolerate stretches and contracts at different times of year," Scheffers said.

The researchers found that in the spring, when nighttime temperatures are still cold and daytime temperatures begin to warm up, mosquitoes can tolerate a larger range of temperatures. Come summer, when daily temperatures are warm, that range contracts. In autumn, when temperatures begin to cool off, the range stretches again, Scheffers explained.

"That tells us that as climate change makes our autumns and winters warmer, mosquitoes in more temperate regions are well prepared to be active during those times," Scheffers said.

"Our results suggest that to better understand how well populations and species may be able to tolerate ongoing climate change, we need to measure species thermal responses across different times of the year," said Brunno Oliveira, the study's first author, who conducted the study while a postdoctoral researcher in Scheffers's lab.

"This information would help us to deliver a more accurate representation of the temperature range a species can tolerate," said Oliveira, now a postdoctoral research at University of California Davis.

For their experiment, the researchers collected the mosquitoes at more than 70 sites around Gainesville and the nearby UF/IFAS Ordway-Swisher Biological Station, a 9,500 acre research and conservation area located about 20 miles east of the city.

The scientists lured mosquitoes with special traps that emit carbon dioxide gas, the same gas that humans and animals exhale when we breath. To a mosquito, a strong whiff of carbon dioxide means a meal is nearby.

With these traps, the researchers caught more than 28,000 mosquitoes representing 18 species. From this collection, the scientists randomly sampled about 1,000 mosquitoes to test in the lab.

Each mosquito was placed in a vial that was then put in a water bath. Over time, the researchers changed the water temperature, increasing or decreasing the temperature inside the vials. The scientists monitored each mosquito's activity, noting when mosquitoes became inactive, a signal that either the upper or lower temperature thresholds were met.

"It was surprising to see how well these little creatures could tolerate high temperatures during the experiments, often well above the mean ambient temperatures measured by the weather stations," said Gécica Yogo, one of the study's co-authors.

Yogo helped conduct the study while she was research scholar trainee at UF as part of her master's program at AgroParisTech in France. She is now a soil carbon engineer at INRAE, the French National Institute for Agriculture, Food and Environment.

The researchers say they don't yet know what allows mosquitoes to adjust to rapid changes in temperature.

"Many people do not realize how quickly natural selection can act on short-lived animals," said Daniel Hahn, professor in the UF/IFAS entomology and nematology department and a co-author of the study. "Whether the changes we are seeing in mosquito thermal properties are due to rapid natural selection across seasons, seasonal plasticity - much like a dog changing its coat -- or a combination of both, is what we are working on now."

The researchers say that insights from this study can help communities better prepare for the impacts of climate change as they relate to mosquitoes, which spread diseases that affect humans and animals.

"The more mosquito activity there is, the greater the risk of these diseases spreading. Knowledge is power, and knowing that mosquitoes will be more active for more of the year can inform how we get ready for climate change," Scheffers said.

Peter Jiang, one of the study's co-authors and an entomologist with City of Gainesville's Mosquito Control division, said that residents play an important role in controlling mosquitoes now and in the future.

Simple actions can keep mosquito populations down, Jiang said.

"Neighbors are encouraged to empty, remove or cover any receptacle that would hold water -- particularly old bottles, tin cans, junk and tires -- repairing leaky pipes, outside faucets and screens, covering or turning small boats upside down, and, twice a week, changing water in wading pools, bird baths, pet dishes and vases holding flowers or cuttings," Jiang said.

Residents looking to learn more about how to control mosquitoes can contact their local UF/IFAS Extension office or their municipal or county mosquito control program.

In addition to informing decision-making, studies like this one bring into focus an aspect of climate change now getting more attention.

"When we talk about how climate change might affect plants and animals, we are often talking about species moving to new areas because the conditions are changing -- in other words, the arrival of something new. However, climate change will also affect species we live with right now, like highly flexible mosquitoes, and that's another aspect to consider," Scheffers said.

Credit: 
University of Florida

URI researchers: New survey method proves Rhode Island's rarest frog may not be so rare

image: The Eastern spadefoot toad, actually a primitive frog, may not be so rare after all according to a study by University of Rhode Island researchers who used a seldom-used methodology that turned up many more of the endangered animals than expected.

Image: 
Anne Devan-Song

KINGSTON, R.I. – June 14, 2021 – The rarest frog in Rhode Island may not be as rare as scientists once thought after a study by University of Rhode Island researchers using a seldom-used methodology turned up many more of the endangered animals than they expected.

Eastern spadefoots – often called spadefoot toads, though they are actually frogs – have long been considered highly secretive and difficult to find outside of their one- or two-day annual breeding periods on rainy nights. In some years, they don’t breed at all. But after scientists reported just 50 sightings of the frogs over the previous 70 years, the Rhode Island researchers observed 42 spadefoots in 10 nights of searching last summer using the new methodology.

“We collected all the myths and misconceptions about spadefoots that have been published or told to us by herpetologists, and we decided to conduct surveys to show that the frogs aren’t secretive, that they don’t only come out when weather is suitable, and they can be detected easily using a noninvasive censusing method,” said Anne Devan-Song, a former URI graduate student who is now a doctoral student at Oregon State University.

While working as a URI research associate in collaboration with Associate Professor Nancy Karraker, Devan-Song led a team that conducted amphibian surveys in Colonial National Historical Park in Virginia from 2015 to 2017 by using a spotlight at night to detect the animals’ eyeshine in forests. A previous researcher conducted amphibian surveys at the park 15 years ago and only detected two Eastern spadefoots, but Devan-Song and her team found up to hundreds of them, even on dry nights, and a total of more than 3,000 individuals.“It completely contradicted everything we’d read about them in the scientific literature, with the exception of recent studies in Massachusetts and Connecticut,” said Devan-Song, whose research was published this month in the Journal of Herpetology. “The perception is that they’re difficult to detect in large numbers outside of rainy weather conditions, but I was stumbling all over them everywhere I went at this particular site, even in drought years when I was nowhere near a known breeding pond.”

To be sure that she could distinguish between the eyeshine of spadefoots and the eyeshine of other creatures active at night – a concern expressed by previous scientists who rejected the spotlighting method – Devan-Song confirmed her ability to accurately identify spadefoot eyeshine by capturing every frog whose eyeshine she detected.

Since the Virginia site may have been home to an uncharacteristically high number of the frogs, Devan-Song collaborated with Rhode Island Department of Environmental Management herpetologist Scott Buchanan to use her spotlighting technique at scattered sites around Rhode Island, where the frogs were believed to be located at only one site and were seldom seen there.

“Spadefoots are at the northern end of their range in Rhode Island and are incredibly rare there,” Devan-Song said. “You can’t just drive around at night and hear them, and there’s little chance of finding them by chance. And yet with just a little bit of spotlighting effort, you can find them.”For sites that were occupied, the frogs were detected on nine out of ten survey nights in Rhode Island, the same rate as they were found in Virginia, and a new breeding population was discovered at a site in Westerly. In both states, the majority of spadefoots observed were sub-adults, an age class seldom detected using traditional survey methods.

“The lack of appropriate methods has hindered the study of this species, which is considered endangered in many states, including Rhode Island,” said Devan-Song. “Without appropriate field methods, you can’t gather information about certain demographic classes and you can’t make accurate population assessments.

“By looking for them only on rainy nights or only near ponds, it has hindered the study of this species for decades,” she added. “There is a huge amount of information that can be collected, especially on these overlooked demographic categories.”

The research team has at least two additional scientific papers in the works that will shed more light on the life history of Eastern spadefoots, both based on the data collected from Rhode Island and Virginia. One describes the social structure of the species, which had been unknown outside the breeding season.

“The general idea had been that these frogs are solitary and don’t interact much except when they go to their ponds to breed,” she said. “But the reality is that they’re doing lots of interesting things in the uplands. Their social structure is much more complex than we imagined.”

Credit: 
University of Rhode Island

Young adults who lost and then restored heart health had lower risk of heart attack, stroke

DALLAS, June 14, 2021 -- Preserving good cardiovascular health during young adulthood is one of the best ways to reduce risks of premature heart attack or stroke, according to new research published today in the American Heart Association's flagship journal Circulation.

The number of premature deaths from cardiovascular disease is increasing in many countries including the U.S. While there is a wealth of information available on maintaining good heart health during and after midlife to reduce the risks of heart attack and stroke, data about cardiovascular health during young adulthood is scarce.

"Most people lose ideal cardiovascular health before they reach midlife, yet few young people have immediate health concerns and many do not usually seek medical care until approaching midlife," says the study's senior author Hyeon Chang Kim, M.D., Ph.D., a professor in the department of preventive medicine at Yonsei University College of Medicine in Seoul, South Korea. "We need strategies to help preserve or restore heart health in this population because we know poor heart health in young adults is linked to premature cardiovascular disease."

Using the Korean National Health Insurance Services, a nationwide health insurer database, Kim and colleagues analyzed information collected from more than 3.5 million adults who completed routine health exams in 2003 and 2004. A subgroup of approximately 2.9 million participants underwent a follow-up health examination between 2005 and 2008. Patients' ages ranged from 20 to 39 at the time of the first exam, and 65.5% of the study participants were male.

Participants were categorized according to ideal cardiovascular health (CVH) scores based on the American Heart Association's Life's Simple 7® metrics. Patients received "one point" towards a cardiovascular health (CVH) score for each of the following measures from Life's Simple 7: well-maintained blood pressure, low total cholesterol, acceptable blood sugar levels, an active lifestyle, healthy weight and not smoking. Of note: healthy nutrition and diet, the final measure of Life's Simple 7, was not included in this analysis because dietary information was not collected from participants in this database.

Researchers evaluated the total number of first hospitalizations or death from a heart attack, stroke or heart failure by December 31, 2019 to define outcomes. The researchers found:

Rates of premature (younger than 55) cardiovascular events were highest among patients with a CVH score of zero.

A higher CVH score by one point led to reduced risks for heart attack by 42%, heart failure by 30%, cardiovascular death by 25% and stroke by 24%.

While people who improved their CVH score over time reduced their risk of hospitalizations or death from a heart attack, stroke or heart failure, people who began with and maintained a higher CVH score ultimately had the least chance of hospitalization or death from a heart attack or stroke during the study period.

Timely and consistent monitoring of heart health among young adults is important to prevent premature onset of heart disease and reduce the risk of cardiovascular events.

The study's findings may be limited because data was routine health screening data, therefore, it may not be as robust as data collected primarily for a specific study. The study also lacks data on the participants' eating patterns, so researchers modified CVH score metrics to exclude diet. In addition, participants in this study were of Korean ancestry, so the results may not be generalizable to people from other diverse racial or ethnic groups.

Credit: 
American Heart Association

Barks in the night lead to the discovery of new species

The raucous calls of tree hyraxes -- small, herbivorous mammals -- reverberate through the night in the forests of West and Central Africa, but their sound differs depending on the location.

Tree hyraxes living between the Volta and Niger rivers make a barking call that is distinct from the shrieking vocalizations of hyraxes inhabiting other regions of the African forest zone.

A new study in the Zoological Journal of the Linnean Society co-authored by Yale anthropologist Eric Sargis finds that the barking hyraxes are a separate species from their shrieking neighbors. The newly described species, Dendrohyrax interfluvialis, populates the wet and dry forests that lie between the two rivers in coastal regions of southeastern Ghana, southern Togo and Benin, and southwestern Nigeria.

The researchers based their conclusion on the distinctive calls combined with anatomical and genetic differences they identified among tree hyrax populations.

"Sometimes a keen ear is as important as a sharp eye," said Sargis, curator of mammalogy and vertebrate paleontology at the Yale Peabody Museum of Natural History. "My co-authors John Oates and Simon Bearder were in Nigeria in 2009 researching galagos, a group of primates, when they noticed that the hyrax calls were different on one side of the Niger from the other. All the evidence we subsequently studied, including the distinctive vocalizations, points to a unique species in the forests between the Niger and the Volta."

Adult tree hyraxes typically weigh between 5 and 7 pounds -- about the size of a groundhog -- but they are closely related to elephants and manatees. They are usually regarded as nocturnal and tree dwelling, but their behavior has proved difficult to study, in part because, unlike most nocturnal mammals in Africa, their eyes don't shine at night, making them more difficult to spot, the researchers explained.

The researchers studied 418 recordings of tree hyrax calls made between 1968 and 2020 at 42 sites in 12 countries. Bearder, emeritus professor at Oxford Brookes University, produced sonograms from a sample of the 96 clearest and most complete recordings, including 34 from the population between the Niger and Volta and 62 from tree hyrax populations across West, Central, and East Africa, measuring their duration, frequency range, and repetition rates, among other characteristics. This analysis revealed that nearly all the calls recorded between the rivers were "rattle-barks" that differed from the shrieking calls recorded on the western side of the Volta and the eastern side of the Niger.

Sargis and co-author Neal Woodman of the U.S. Geological Survey and the Smithsonian National Museum of Natural History also studied the skulls of 69 adult tree hyrax specimens from six museum collections in Europe and North America. They found subtle but clear differences in the shape and size of skulls from specimens collected between the rivers and those gathered elsewhere. The skulls of D. interfluvialis were shorter and broader than those of their counterparts from outside the interfluvial zone, the study found.

An examination of museum skins, carcasses of hyraxes killed by hunters, and camera-trap imagery obtained in Ghana by co-author Edward Wiafe of the University of Environment and Sustainable Development revealed differences in fur color between D. interfluvialis and other populations, with the flanks and limbs of the former being brindled dark brown and lighter yellow-brown while the latter are dark brown to nearly black. Finally, genetic analyses of 21 samples of hyrax tissue from across the African rainforest found that the interfluvial populations were genetically distinct from other hyrax lineages, according to the study.

Oates, emeritus professor of anthropology at Hunter College in New York City, coordinated the study's various analyses. He has been studying the biogeography of the region inhabited by the newly described species since 1964, when he first heard the nocturnal calls of tree hyraxes on Bioko Island.

"There is increasing evidence that the Niger and Volta Rivers are significant biogeographic barriers to a range of mammals," Oates said. "Hyraxes, for instance, don't cross water easily, so it makes sense that, through millions of years of changing climate, as African forests have expanded and contracted, new species would have differentiated in isolated forest fragments known as refugia, and then have been limited in their subsequent dispersal by large rivers."

As a result, the region between the Volta and Niger now contains many unique animal species, the authors explain. The researchers warn, however, that the wildlife of the region between the Volta and Niger is under severe threat due to large and still growing human populations. Its forests have been reduced to fragments through a combination of commercial logging, tree cutting for firewood and charcoal production, plantation agriculture, and subsistence farming, they note, while most of the larger mammals are hunted for their meat. They call for increased efforts to create effective new nature reserves.

Credit: 
Yale University

Radiotracer effective for detection and assessment of lung fibrosis

image: A) Axial CT images through the mouse lungs at 7 and 14 days after intratracheal administration of bleomycin or saline (as a control), demonstrating increased lung fibrosis in the bleomycin group (white arrows). (B) CT attenuation histograms in Hounsfield units (HU) after lung segmentation demonstrate increased attenuation in the lungs in the bleomycin group than the control group (p

Image: 
Image created by CA Ferreira et al., University of Wisconsin-Madison, Madison, WI.

Reston, VA (Embargoed until 4:30 p.m. EDT, Saturday, June 12, 2021)--Positron emission tomography (PET) using a 68Ga-labeled fibroblast activation protein inhibitor (FAPI) can noninvasively identify and monitor pulmonary fibrosis, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting. By binding to activated fibroblasts present in affected lungs, FAPI-PET allows for direct imaging of the disease process.

Idiopathic pulmonary fibrosis (IPF) causes substantial scarring to the lungs, making it difficult for those impacted to breathe. It is a significant cause of morbidity and mortality in the United States, with more than 40,000 deaths annually. A major challenge in diagnosis and treatment of IPF is the lack of a specific diagnostic tool that can noninvasively diagnose and assess disease activity, which is crucial for the management of pulmonary fibrosis patients.

"CT scans can provide physicians with information on anatomic features and other effects of IPF but not its current state of activity. We sought to identify and image a direct noninvasive biomarker for early detection, disease monitoring and accurate assessment of treatment response," said Carolina de Aguiar Ferreira, PhD, a research associate at the University of Wisconsin-Madison in Madison, Wisconsin.

In the study, researchers targeted the fibroblast activation protein (FAP) that is overexpressed in IPF as a potential biomarker. Two groups of mice--one group with induced pulmonary fibrosis and one control group--were scanned with the FAPI-based PET/CT radiotracer 68Ga-FAPI-46 at multiple time points. Compared to the control group, the mice with induced pulmonary fibrosis had a much higher uptake of the radiotracer, allowing researchers to successfully identify and evaluate areas of IPF.

"Further validation of 68Ga-FAPI-46 for the detection and monitoring of pulmonary fibrosis would make this molecular imaging tool the first technique for early, direct, and noninvasive detection of disease. It would also provide an opportunity for molecular imaging to reduce the frequency of lung biopsies, which carry their own inherent risks," noted Ferreira. "This development will demonstrate that functional imaging can play an invaluable role in evaluation of the disease process."

Abstract 10. "Targeting Activated Fibroblasts for Non-invasive Detection of Lung Fibrosis," Carolina Ferreira, Zachary Rosenkrans, Ksenija Bernau, Jeanine Batterton, Christopher Massey, Alan McMillan, Nathan Sandbo, Ali Pirasteh and Reinier Hernandez, University of Wisconsin - Madison, Madison, Wisconsin; and Melissa Moore, Frank Valla and Christopher Drake, Sofie Biosciences, Dulles, Virginia.

Credit: 
Society of Nuclear Medicine and Molecular Imaging