Culture

Evidence-based vocational rehab practices raise employment rates after spinal cord injury

image: Dr. O'Neill is director of the Center for Employment and Disability Research at Kessler Foundation.

Image: 
Kessler Foundation

East Hanover, NJ. September 18, 2020. Researchers at Kessler Foundation authored a new article, "Employment after spinal cord injury," (DOI: 10.1007/s40141-020-00266-4), published by Current Physical Medicine and Rehabilitation Reports on May 24, 2020. Authored by John O'Neill, PhD, and Trevor Dyson-Hudson, MD, the article highlights evidence-based practices in vocational rehabilitation. It is featured in SpringerLink's Collection on Topics in Spinal Cord Injury Rehabilitation.

Link to abstract: https://link.springer.com/article/10.1007/s40141-020-00266-4

Despite the challenges, people strive to work after spinal cord injury. Research shows that employment has meaning, value, and benefits for people with spinal cord injury. In addition to the evident economic benefits, people value their identity as members of the workforce, and the social status that accompanies inclusion in society.

Work is an important part of all of our lives and that should be no different for people with spinal cord injury. In fact, studies show that people who work after spinal cord injury have better quality of life and less depression, as well as better health and longevity, according to Dr. Dyson-Hudson, director of the Center for Spinal Cord Injury Research at Kessler Foundation.

"Achieving success in the workplace after spinal cord injury is more likely when individuals have access to transportation and assistive technology," he said, "and when secondary medical complications are minimized. Education clearly correlates with success," he continued, "and studies show that post injury educational attainment can be particularly beneficial for individuals with spinal cord injury."

The authors detail advances in vocational rehabilitation research that are increasing the numbers of individuals with spinal cord injury transitioning to competitive employment. Integrating employment services into spinal cord injury rehabilitation supports the feasibility of returning to work, and focuses the efforts of the team on the individual's goal of returning to work.

Evidence-based practices that are raising post-injury employment rates include the individualized placement support (IPS) model of supported employment (SE), and vocational resource facilitation (VRF), an early intervention model, according to Dr. O'Neill, director of the Center for Employment and Disability Research at Kessler Foundation. Dr. O'Neill described the results achieved with IPS-SE in veterans with spinal cord injury: "Studies conducted in the Veterans Administration Hospital system showed employment rates of 26% with IPS-SE versus 11% with traditional vocational rehabilitation services."

Dr. O'Neill also pointed to the gains seen with the implementation of VRF for newly injured individuals in a project funded by Craig H. Neilsen Foundation. "Of the patients recruited during inpatient rehabilitation at Kessler Institute for Rehabilitation, 43% have returned to work, significantly exceeding national one-year post injury benchmarks ranging from 12% to 21%."

The authors concluded that employment outcomes after spinal cord injury can be improved by providing necessary supports, minimizing secondary medical complications, and implementing effective employment interventions.

Credit: 
Kessler Foundation

Bolsonaro's Indigenous land mining policy a billion-dollar backfire

image: "Brazil's Indigenous Lands are unbelievably valuable - socially, ecologically and economically," Ms Siqueira-Gay said.

Image: 
Juliana Siqueira-Gay

Research has found a proposal to regulate mining of Indigenous lands in Brazil's Amazon rainforest could affect more than 863,000 square kilometres of forest and harm the nation's economy.

Led by University of Queensland visiting PhD student Juliana Siqueira-Gay, an international collaboration has warned that President Jair Bolsonaro's 2020 bill to mine inside recognised Indigenous Lands would come at a cost.

"Brazil's Indigenous Lands are unbelievably valuable - socially, ecologically and economically," Ms Siqueira-Gay said.

"They're a unique category of protected area, covering 1.2 million square kilometres - or 23 per cent - of what is legally recognised as the Amazon.

"The Brazilian government wants to capitalise on this value, by bolstering the economy through extending mining.

"But we've calculated that this proposed policy - introduced in February this year - could lead to millions, if not billions, of dollars in losses each year.

"The loss would be primarily due to effects on rubber, timber and Brazil nut production, increased damage to greenhouse gas mitigation ecosystem services and other vital ecosystem services.

"It's a portfolio of ecological assets currently providing Brazil an estimated $7 billion AUD - it simply makes no financial sense to destroy something so valuable."

The researchers, based in both Brazil and Australia, crunched existing data and reviewed potential mining locations, quantifying threats from mining to forests and their ecosystems.

"The figures were astonishing - it's clear that much of the Amazon is at threat from this proposed policy, including extremely rare ecosystems conservation and incredibly diverse Indigenous groups and their culture" Ms Siqueira-Gay said.

"If the 4,600 known mineral deposits existing outside currently protected areas were to be developed, you're looking at 698-thousand square kilometres of forests to be potentially affected.

"But, with the approval of this proposed policy, that affected area could increase by 20 per cent, up to 863-thousand square kilometres.

"This increase alone is roughly the same size as Belgium, the Netherlands, Switzerland, Denmark and Israel combined."

Study collaborator, Dr Laura Sonter, said she had real concerns for these forests and their supported communities, and hoped the research was heeded by the international community.

"If President Bolsonaro's bill is approved by Brazil's congress, there'll be a cascade of negative effects, both domestically in Brazil and internationally," Dr Sonter said.

"These lands are home to 222 Indigenous groups, with more than 644 thousand families living in traditional communities and speaking 160 languages.

"So, beyond economic costs to the nation, the lives of Indigenous communities will be permanently altered, and there will be significant environmental impacts.

"We hope this data can help the Brazilian government, and people, make smart decisions and protect these precious lands."

Credit: 
University of Queensland

Mapping the 1.6 billion people who live near forests

image: This photograph, taken in the Médio Juruá region of Amazonas State, Brazil. shows the houses of forest-proximate people living in sustainable development reserves in Amazonia.

Image: 
Peter Newton, University of Colorado Boulder

Global maps of places where people and forests coexist show that an estimated 1.6 billion people live within 5 kilometers of a forest. The assessment, based on data from 2000 and 2012 and published September 18 in the journal One Earth, showed that of these 1.6 billion "forest-proximate people," 64.5 percent were located in tropical countries, and 71.3 percent lived in countries classified as low or middle income by the World Bank.

"There were no data at all on how many people live in and around forests globally," says first author Peter Newton, an Assistant Professor in Environmental Studies at the University of Colorado Boulder. "The exercise was an initial step of trying to quantify the potential target population for projects that look at people's livelihoods in a forest environment."

People who rely on forest resources for subsistence or income are commonly known as forest-dependent people. Although the number of forest-proximate people coincidently matches the 1.6 billion forest-dependent people from a widely cited estimation from the World Bank, living near the forest doesn't necessarily mean one relies on the forest for livelihood. Newton says that while "forest-dependent people" widely refers to people who derive some benefits from forests, the term "forest-proximate people" merely captures the spatial relationship between people and forests.

"Large numbers of people do live in and around forests, so that makes forests an important habitat and biome for thinking about sustainable development as well as about conservation," says Newton. "The programs, projects, and policies that affect forests also affect large numbers of people."

To map out the spatial relationship between people and forests globally, Newton and his colleagues combined forest cover and human population density data for the year 2000 and 2012. They counted the number of people who lived within 5 km (3.1 miles) from the border of forests, which they defined as any area with more than 50 percent tree cover over 2 hectares (5 acres). But they excluded urban areas with a population above 1,500 people per square kilometer (0.4 square miles).

The work provides a sketch to which other researchers and decision-makers could add on different layers of data, such as social, economic, or cultural details to paint a more complete picture. However, many of these datasets aren't available at a global level.

"What other researchers or we could do in the future is home in on a particular region where we did have data," says Newton. From local data, scientists could infer how many of those forest-proximate people were also forest dependent or living in poverty to help decision-makers implement spatial targeting and impact assessment.

Credit: 
Cell Press

Yale succeeds with a more inclusive approach to heart transplants

New Haven, Conn. -- Doctors at Yale New Haven Hospital used a more aggressive selection process to more than quadruple the number of heart transplants performed there while maintaining positive patient outcomes, according to a new study.

The findings suggest that a more inclusive approach to selecting donor hearts and transplant recipients can enable hospitals to successfully treat more patients in need of transplants. The study appears online Sept. 18 in the journal JAMA Network Open.

The study looked at short-term patient outcomes for two groups: 49 patients who received heart transplants from 2014 to 2018, and 58 patients who had their heart transplants in the year after the hospital adopted a more aggressive selection process for donor recipients (2018-2019).

The more aggressive selection process significantly shortened the waiting period for heart patients, from 242 days to 41 days, the researchers said. Importantly, patients' survival rate at 180 days after the transplant remained nearly unchanged.

The expansion of heart transplant procedures at the hospital, in September 2018, coincided with the implementation of the new United Network for Organ Sharing (UNOS) donor heart allocation system in the United States.

"I think this is the takeaway for other centers -- that such a change in the approach could create opportunities for patients in need while maintaining outcomes in the short term," said Makoto Mori, M.D., a surgical resident at Yale and first author of the study.

The senior author of the study was Harlan Krumholz, M.D., the Harold H. Hines Jr. Professor of Medicine (cardiology) and director of Yale's Center for Outcomes Research and Evaluation.

In practical terms, the expansion of heart transplant procedures at Yale New Haven Hospital meant accepting hearts from older donors with additional medical conditions, as well as accepting transplant recipients with more severe illnesses.

Yale New Haven Hospital also changed the surgical leadership of its advanced heart failure program, hired a dedicated procurement surgeon and an additional transplant coordinator, and increased the involvement of surgical attending physicians.

The researchers noted that Yale's increase in heart transplant cases was significantly larger than the volume change seen at other heart transplant centers in the same region during the same period, including Hartford Hospital, Tufts Medical Center, Brigham and Women's Hospital, and Massachusetts General Hospital.

"We used a multidisciplinary approach and made strategic changes in donor and recipient selection, which allowed us to increase the number of heart transplants performed and therefore help more patients with advanced heart failure in a safe and an effective manner," said co-author Arnar Geirsson, M.D., chief of cardiac surgery at Yale New Haven Hospital.

Co-authors of the study were Lynn Wilson, Tariq Ahmad, Muhammad Anwer, and Daniel Jacoby, all of Yale; and Ayyaz Ali of Hartford Hospital.

Credit: 
Yale University

Knowledge gained, questions remain on severe COVID-19 infections

What The Editorial Says: Authors of this editorial review the evidence for the management of patients with the acute respiratory distress syndrome (ARDS) that may apply to patients with severe COVID-19, what has been learned about treatment of these patients, and the gaps in knowledge that remain.

Authors: Carolyn S. Calfee, M.D., M.A.S., of the University of California, San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.6047)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full editorial is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.6047?guestAccessKey=197f4dec-8362-4aab-9525-c1fe6e78bf66&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=091820

Credit: 
JAMA Network

VLBA makes first direct distance measurement to magnetar

Astronomers using the National Science Foundation's Very Long Baseline Array (VLBA) have made the first direct geometric measurement of the distance to a magnetar within our Milky Way Galaxy -- a measurement that could help determine if magnetars are the sources of the long-mysterious Fast Radio Bursts (FRBs).

Magnetars are a variety of neutron stars -- the superdense remains of massive stars that exploded as supernovae -- with extremely strong magnetic fields. A typical magnetar magnetic field is a trillion times stronger than the Earth's magnetic field, making magnetars the most magnetic objects in the Universe. They can emit strong bursts of X-rays and gamma rays, and recently have become a leading candidate for the sources of FRBs.

A magnetar called XTE J1810-197, discovered in 2003, was the first of only six such objects found to emit radio pulses. It did so from 2003 to 2008, then ceased for a decade. In December of 2018, it resumed emitting bright radio pulses.

A team of astronomers used the VLBA to regularly observe XTE J1810-197 from January to November of 2019, then again during March and April of 2020. By viewing the magnetar from opposite sides of the Earth's orbit around the Sun, they were able to detect a slight shift in its apparent position with respect to background objects much more distant. This effect, called parallax, allows astronomers to use geometry to directly calculate the object's distance.

"This is the first parallax measurement for a magnetar, and shows that it is among the closest magnetars known -- at about 8100 light-years -- making it a prime target for future study," said Hao Ding, a graduate student at the Swinburne University of Technology in Australia.

On April 28, a different magnetar, called SGR 1935+2154, emitted a brief radio burst that was the strongest ever recorded from within the Milky Way. While not as strong as FRBs coming from other galaxies, this burst suggested to astronomers that magnetars could generate FRBs.

Fast radio bursts were first discovered in 2007. They are very energetic, and last at most a few milliseconds. Most have come from outside the Milky Way. Their origin remains unknown, but their characteristics have indicated that the extreme environment of a magnetar could generate them.

"Having a precise distance to this magnetar means that we can accurately calculate the strength of the radio pulses coming from it. If it emits something similar to an FRB, we will know how strong that pulse is," said Adam Deller, also of Swinburne University. "FRBs vary in their strength, so we would like to know if a magnetar pulse comes close or overlaps with the strength of known FRBs," he added.

"A key to answering this question will be to get more distances to magnetars, so we can expand our sample and obtain more data. The VLBA is the ideal tool for doing this," said Walter Brisken, of the National Radio Astronomy Observatory.

In addition, "We know that pulsars, such as the one in the famous Crab Nebula, emit 'giant pulses,' much stronger than their usual ones. Determining the distances to magnetars will help us understand this phenomenon, and learn if maybe FRBs are the most extreme example of giant pulses," Ding said.

The ultimate goal is to determine the exact mechanism that produces FRBs, the scientists said.

Credit: 
National Radio Astronomy Observatory

Most homemade masks are doing a great job, even when we sneeze, study finds

image: Researchers tested 11 household fabrics that are commonly used for homemade masks and found that all are effective at curbing the small and large respiratory droplets that are released when we speak, cough or sneeze.

Image: 
Graphic by Michael Vincent

CHAMPAIGN, Ill. — Studies indicate that homemade masks help combat the spread of viruses like COVID-19 when combined with frequent hand-washing and physical distancing. Many of these studies focus on the transfer of tiny aerosol particles; however, researchers say that speaking, coughing and sneezing generates larger droplets that carry virus particles. Because of this, mechanical engineer Taher Saif said the established knowledge may not be enough to determine the effectiveness of some fabrics used in homemade masks.

Saif, a mechanical science and engineering professor at the University of Illinois, Urbana-Champaign, led a study that examined the effectiveness of common household fabrics in blocking droplets. The findings are published in the journal Extreme Mechanics Letters.

Aerosol particles are typically classified as less than 5 micrometers, and lie in the range of hundreds of nanometers. However, larger droplets – up to about 1 millimeter in diameter – can  also be expelled when an individual speaks, coughs or sneezes. These larger droplets pose a problem because, with sufficient momentum, they can squeeze through the pores of some fabrics, break into smaller droplets and become airborne.

However, for an individual to feel compelled to wear a mask, it must be comfortable and breathable, the researchers said.

“A mask made out of a low-breathability fabric is not only uncomfortable, but can also result in leakage as the exhaled air is forced out around contours of a face, defeating the purpose of the mask and providing a false sense of protection,” Saif said. “Our goal is to show that many common fabrics exploit the trade-off between breathability and efficiency of blocking droplets – large and small.”

The team tested the breathability and droplet-blocking ability of 11 common household fabrics, using a medical mask as a benchmark. The fabrics selected ranged from new and used garments, quilted cloths, bedsheets and dishcloth material. The researchers then characterized the fabrics in terms of their construction, fiber content, weight, thread count, porosity and water-absorption rate.

“Testing the breathability of these fabrics was the easy part,” Saif said. “We simply measured the rate of airflow through the fabric. Testing the droplet-blocking ability is a bit more complicated.”

In the lab, the researchers fill the nozzle of an inhaler with distilled water seeded with easy-to-find 100-nanometer diameter fluorescent particles – which happens to be the size of a novel coronavirus particle. When puffed, the inhaler forces the water through the nozzle and generates high-momentum droplets that collect on a plastic dish placed in front of the inhaler. To test the fabrics, the researchers repeat this process with the various materials placed over the collection dishes.

“We count the number of nanoparticles landing on the dish using a high-resolution confocal microscope. We can then use the ratio of the number collected with and without the fabric to give us a measure of droplet-blocking efficiency,” Saif said.

The team also measured the velocity and size of the particles expelled from the inhaler using high-speed video.

Their analyses revealed that droplets leave the inhaler at about 17 meters per second. Droplets released by speaking, coughing and sneezing have velocities within the range of 10 to 40 meters per second, the researchers said.

In terms of size, the high-speed video detected droplets with diameters in the 0.1 to 1 millimeter range, matching that of the larger-sized droplets released by speaking, coughing and sneezing.

 “We found that all of the fabrics tested are considerably effective at blocking the 100 nanometer particles carried by high-velocity droplets similar to those that may be released by speaking, coughing and sneezing, even as a single layer,” Saif said. “With two or three layers, even the more permeable fabrics, such as T-shirt cloth, achieve droplet-blocking efficiency that is similar to that of a medical mask, while still maintaining comparable or better breathability.

“Our experimental platform offers a way to test fabrics for their blocking efficiency against the small – and now – larger droplets that are released by human respiratory events.”

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

After developing CRISPR test, UConn researchers validate clinical feasibility for COVID-19 testing

In March, researchers in the Department of Biomedical Engineering-- a shared department in the schools of Dental Medicine, Medicine, and Engineering--began to develop a new, low-cost, CRISPR-based diagnostic platform to detect infectious diseases, including HIV virus, the novel coronavirus (SARS-CoV-2). Today, the method is one step closer to being a cutting-edge diagnostics technology for rapid detection of infectious diseases.

Lead by associate professor Changchun Liu, the "All-In-One-Dual CRISPR-Cas12a" (AIOD-CRISPR) method enables simple, rapid, ultrasensitive, visual detection of SARS-CoV-2, intended for use at home or in small clinics.

In a paper published in Nature Communications, the researchers validated the clinical feasibility of the platform using COVID-19 clinical swab samples. Additionally, the researchers used a low-cost hand warmer as an incubator to detect clinical sample results within 20 minutes.

"The usage of disposable hand warmers to heat the AIOD-CRISPR assay eliminates need for expensive electric equipment, enabling instrument-free point of care molecular diagnostics of COVID-19," says Liu.

The publication was co-authored by postdoctoral researchers Xiong Ding and Kun Yin; PhD student Ziyue Li; professor and Associate Dean for Research Dr. Rajesh Lalla; Dr. Enrique Ballesteros, associate professor and chair, pathology and laboratory medicine; and Dr. Maroun Sfeir, assistant professor in pathology and laboratory medicine.

Nucleic acid amplification testing (PCR/RT-PCR) is currently the most sensitive and specific method for early detection of pathogens, but is not suitable for rapid point-of-care diagnostics because of the need for specialized laboratory equipment and trained technicians. Highly contagious pathogens, however, need real-time monitoring to prevent spreading from person to person.

In the study, Liu and his team evaluated their AIOD-CRISPR method using the RNA extract of 28 clinical COVID-19 swab samples, which included eight COVID-19 positive samples. To ensure the reliability of detection, each sample was tested twice in two independent trials. All eight of the COVID-19 positive samples were identified as positive in 40 minutes, which was also confirmed by visual detection. The results were also consistent with those of the CDC-approved RT-PCR method.

The researchers also used a low-cost hand warmer as an incubator to detect the patient samples to eliminate the need for an electric incubator. The AIOD-CRISPR tubes were directly placed on an air-activated hand warmer, and the results were visible by the naked eye under LED light. Two COVID-19 positive samples incubated in the hand warmer bag were visually detected and identified as positive in 20 minutes.

"Such simple, portable and sensitive detection platform has the potential to provide rapid and early diagnostics of COVID-19 and other infectious diseases at home, in doctor's office, and even at drive-thru testing sites," says Liu.

Credit: 
University of Connecticut

Increasing the effectiveness of immunotherapy against skin cancer

image: Prof. Dr. phil. nat. Mirjam Schenk, Institute of Pathology, University of Bern.

Image: 
Courtesy of Mirjam Schenk

The melanoma is a malignant tumor of the pigment cells. If diagnosed early, the tumor can be removed completely - and the chances of recovery are good. But in later stages, when the tumor has already spread or formed metastases in other parts of the body, the prospects become worse for those affected.

No effect for a good half of patients

The so-called immune checkpoint inhibitors, which have been approved in the last ten years, are a ray of hope - and the medical profession has achieved spectacular treatment successes with these medicines. However, in a good half of all patients these therapies show no benficial effect.

But now, the work of the research group led by Mirjam Schenk from the Institute of Pathology at the University of Bern shows a promising way of increasing the effectiveness of the treatment and helping many more patients than before.

In collaboration with researchers from the USA, the team led by Schenk has uncovered the role of a signal molecule which the cells of the body's immune system use to coordinate their functions.

The molecule is called Interleukin-32, IL-32 for short. In the complex interplay of immune cells within and in the immediate area around a tumor, it soon revealed a double effect. "It hits two birds with one stone," says Schenk.

Making tumors attackable again

On one hand, IL-32 leads to the maturation and activation of so-called dendritic cells which are responsible for the recognition of foreign structures. In addition, IL-32 also triggers macrophages or scavenger cells to secrete attractants for the T cells. This is how these immune cells find their way to the tumor, where they can eliminate the cancer cells.

Tumors have to escape detection by the immune system for them to be able to grow. This is why they settle in immunosuppressed environments which are hospitable for cancer growth. Clearly, IL-32 is capable of making these protective niches of the tumor accessible to the immune system again.

With trials on mice, the researchers led by Schenk have proven that the efficacy of immune checkpoint inhibitors can be improved by the simultaneous administration of IL-32.

Combination treatment a "promising therapeutic strategy"

In animal models, the additionally administered IL-32 did not cause any side effects. Whether these results can be transferred to humans remains to be seen, says Schenk. However, a further argument certainly speaks for the fact that the combination treatment represents a "promising strategy for treatment", as the researchers led by Schenk write in their recently published specialist article in the &laquoThe Journal of Clinical Investigation insight».

As they have been able to prove with bioinformatic analyses, melanoma patients with more IL-32 activity have an improved life expectancy, from a statistical point of view.

Credit: 
University of Bern

New roles for clinicians in the age of artificial intelligence

Announcing a new article publication for BIO Integration journal. In this opinion article the authors Fengyi Zeng, Xiaowen Liang and Zhiyi Chen from The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China consider new roles for clinicians in the age of artificial intelligence (AI).

With the rapid developments of digital picture processing, pattern recognition, and intelligent algorithms, artificial intelligence (AI) applications are now widely used in medicine. Applications of artificial intelligence in medicine (AIM) include diagnosis generation, therapy selection, healthcare management and disease stratification. AIM focuses on assisting clinicians in disease detection, quantitative measurements, and differential diagnosis which improves diagnostic accuracy and optimizes treatment selection.

However, there is little research on the consideration of clinicians in the age of AI. Concerns have been raised as to whether doctors will eventually be replaced by AI. From this viewpoint, the authors elaborate on the unlikelihood of AI completely replacing doctors and explore how doctors can adapt their roles to assist successful integration of AI into current medical techniques and procedures.

Credit: 
Compuscript Ltd

Researchers discover a novel family of toxins used in bacterial competition

image: fluorescence image of bacteria attacked by bacterial toxin.

Image: 
Ethel Bayer-Santos

By André Julião | Agência FAPESP – Researchers at the University of São Paulo (USP) in Brazil have characterized a novel family of anti-bacterial toxins present in bacteria, including Salmonella enterica. This species uses toxic proteins to kill other bacteria in gut microbiota and facilitate colonization of the infected host’s gut.

The study is published in Cell Reports and featured on the cover of the journal.

The novel family’s founding member is the protein Tlde1 (type VI L,D-transpeptidase effector 1), which attacks bacterial cell wall precursors. It is secreted via the type VI secretion system or T6SS. Targeted bacteria continue growing but because their cell walls are weakened they eventually die as cell contents leak owing to osmotic pressure and lysis.

“This family of toxins has a hitherto undescribed mechanism. While other anti-bacterial toxins secreted by the same system destroy the already formed cell walls of target bacteria, this one acts on precursors so that they’re weak or cannot form at all,” said Ethel Bayer-Santos, a researcher in the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and principal investigator for the project, which is supported by FAPESP.

In a previous study, a research group that included Bayer-Santos described another secretion system (T4SS) in opportunistic bacteria of the species Stenotrophomonas maltophilia. They also described a toxin that inhibits bacterial growth (read more at: agencia.fapesp.br/32157).

“Bacteria selected these toxins during evolution and have been using them for thousands of years, so these discoveries point to therapeutic targets. Bacterial toxins may always have biotechnological potential and become anti-bacterial compounds in the future,” Bayer-Santos said.

Search

In their search for the protein Tlde1, the scientists analyzed the genome of Salmonella in the region neighboring the genes that encode the structural proteins in the secretion system (T6SS). They found a pair of genes with traits that signaled a toxic protein and another that conferred immunity. Anti-bacterial toxins are usually located in bacterial genomes near proteins that contain antidotes to the toxins. These antidotes are required to protect the microorganisms from their own weapons.

To test the function of this gene pair, the researchers first expressed a gene they thought was probably responsible for the toxic protein in a susceptible bacterium, Escherichia coli. It survived when the probable toxic gene was expressed in cytoplasm but died when expression occurred in periplasm, suggesting the toxin targets some structure in this part of the cell wall.

Next, they expressed in E. coli’s periplasm both the toxic protein and the probable immunity protein. This co-expression neutralized the toxic effect and the bacteria survived, confirming that the proteins in question are indeed a toxin and an immune protein respectively.

In evolutionary terms, T6SS is related to the apparatus of bacteriophages, viruses that infect bacteria. It comprises 13 structural proteins that are assembled into a weapon resembling a spear or harpoon with a sharp tip inside a retractable cytoplasmic sheath. The attacking cell ejects the harpoon full of toxic proteins from the sheath into the target cell.

Bioinformatics analysis showed that members of the Tlde1 family are present in several species of bacterium and that the family probably evolved from bacterial enzymes with a key role in cell wall synthesis. The next step in the project is an effort to understand by structural biology how an enzyme that had this role has ended up doing the opposite.

The first authors of the published paper are Stephanie Sibinelli-Sousa and Julia Takuno Hespanhol, who received scientific initiation scholarships (respectively grant no. 18/13819-1 and grant no. 18/25316-4). Sibinelli-Sousa is currently researching for a master’s degree at ICB-USP with FAPESP’s support.

The other authors are Gianlucca Gonçalves Nicastro, Robson Francisco de Souza and Cristiane Rodrigues Guzzo Carvalho, all of whom are affiliated with ICB-USP; Bruno Yasui Matsuyama, affiliated with the same university’s Chemistry Institute (IQ-USP); and Stephane Mesnage and Ankur Patel of Sheffield University in the UK.

The article “A family of T6SS antibacterial effectors related to l,d-transpeptidases targets the peptidoglycan” can be read at: www.cell.com/cell-reports/fulltext/S2211-1247(20)30794-4.

Journal

Cell Reports

DOI

10.1016/j.celrep.2020.107813

Credit: 
Fundação de Amparo à Pesquisa do Estado de São Paulo

Rochester researchers document an optical fiber beyond compare

image: The anti-resonant hollow core fiber features a unique arrangement of seven hollow capillaries arranged around a hollow core inside the fiber.

Image: 
Arjun Iyer/Renninger lab/University of Rochester

A new hollow optical fiber greatly reduces the "noise" interfering with the signals it transmits compared to the single-mode fibers now widely used, researchers at the University of Rochester report.

The anti-resonant hollow-core fiber, created by researchers at the University of Central Florida, produces a thousand times less "noise" - and the lowest levels ever recorded from interference caused by acoustic phonons arising from the glass in the fiber at room temperatures.

To document this, researchers in the lab of William Renninger, assistant professor of optics, developed a highly sensitive measuring technique. Their findings are reported in a paper published in APL Photonics.

"It's a very valuable fiber, and despite a lot of interest in it by researchers and some companies, nobody had really studied the behavior of phonons supported by the structure, and to what extent it actually reduced 'noise,' " says Renninger, an expert in experimental and theoretical nonlinear optics.

The lab's findings conclusively demonstrate that the fiber is a "promising platform for low noise applications, such as for quantum information processing and optical communications," writes lead author Arjun Iyer, a graduate research associate in Renninger's lab.

A unique answer to 'noise'

"Noise" refers to any disturbance that masks or disrupts a signal being sent by light through an optical fiber. One such disturbance is caused by phonons - quantized acoustic or sound waves that occur at atomic and subatomic levels, in this case in the glass of an optical fiber.

Phonons cause a beam of light to "scatter" off the acoustic waves, creating splinter beams of different frequencies, or colors, that can interfere with, and reduce the energy of, the main beam. While some forms of scattering can be useful for specific applications, it interferes with quantum applications and even basic optical communications.

Noise can be reduced by cooling the fibers to extremely low, cryogenic temperatures, but that's "very expensive and complicated," Renninger says. Another approach is to attempt to use complicated error-correcting algorithms to correct for noise.

The anti-resonant hollow-core fiber, however, represents a straightforward solution that works even at room temperatures. Created by co-author Rodrigo Amezcua Correa and other researchers at CREOL, the College of Optics and Photonics at the University of Central Florida, the fiber features a unique arrangement of seven hollow capillaries arranged around a hollow core inside the fiber.

This results in minimal overlap between the fiber's outer layer of glass and the light traveling through the core, eliminating interference from acoustic phonons emanating from the glass.

Tests by Renninger's lab showed that the arrangement is 10 times more effective at reducing noise than other hollow fiber designs. "The little noise that's left is caused by acoustic waves in the air inside the fiber, so if you were to evacuate the air it would be another 100 times more effective," Renninger says. "You would have incredibly low noise".

"If the fate of the world depended on reducing acoustic noise in optical fibers, this is the one you would want to use."

Credit: 
University of Rochester

new alteration in the brain of people with Alzheimer's discovered

Despite the important advances in research in recent years, the etiopathogenesis of Alzheimer's disease is still not fully clarified. One of the key questions is to decipher why the production of beta amyloid, the protein that produces the toxic effect and triggers the pathology, increases in the brain of people with Alzheimer's.

The research has focused on the different fragments of the Amyloid Precursor Protein (APP) until now, but the results have been inconclusive, "because this protein is processed so quickly that its levels in the cerebrospinal fluid or in the plasma do not reflect what is really happening in the brain," explains Dr. Javier Sáez-Valero, head of the group on "Altered Molecular Mechanisms in Alzheimer's Disease and other Dementias" at the UMH-CSIC Neuroscience Institute in Alicante.

Dr. Sáez-Valero's laboratory has carried out a novel approach that shows great promise: "We have discovered that the glycosylation of the amyloid precursor in the brain of Alzheimer's patients is altered. And, therefore, this protein is probably being processed in a different way. We believe that this different way of processing leads to more beta-amyloid, and to the triggering of the pathology".

Glycosylation consists of adding carbohydrates to a protein. This process determines the destiny of the proteins to which a sugar chain (glycoproteins) has been added, which will be secreted or will form part of the cellular surface, as in the case of the Amyloid Precursor Protein (APP). The alteration of this glycosylation process is related with the origin of various pathologies.

In the specific case of Alzheimer's, the results of the study led by Sáez Valero suggest that the altered glycosylation could determine that the APP is processed by the amyloidogenic (pathological) pathway, giving rise to the production of the beta-amyloid, a small protein with a tendency to cluster forming the amyloid plaques characteristic of Alzheimer's disease.

"The fact that the glycosylation of the amyloid precursor is altered indicates that this amyloid precursor may be located into areas of the cell membrane that are different from the usual, interacting with other proteins and therefore probably being processed in a pathological way," clarifies this expert in Alzheimer's disease.

With this new finding of Dr. Saez-Valero's group, published in Alzheimer's Research & Therapy, "analyzing the glycosylation of beta-amyloid fragments opens the possibility of finding a good biomarker for diagnosis in the short term. And in the longer term to intervene therapeutically".

Previously, amyloid fragments of APP had been studied in the cerebrospinal fluid for these purposes, "but the results did not indicate that it could be a good diagnostic marker. However, in view of our new results, we propose to repeat the studies carried out to date not only by looking at the different types of fragments of the beta-amyloid protein, but also at its glycosylation," highlights Sáez-Valero.

The presence of the beta-amyloid protein in the cerebrospinal fluid does not provide much information at present either, "since in the brain this small protein forms amyloid plaques, thus, the paradox is that in the cerebrospinal fluid there are lower levels than would be expected," explains Sáez-Valero.

The other option is to study the long fragments of the APP, "but they are processed so quickly that they do not really reflect anything pathological. However, looking at the glycosylation we have seen that, although the total levels are not altered, there is an indication that the protein is synthesized differently and therefore can be processed in a different way, giving rise to the toxic cascade that triggers Alzheimer's disease," this expert points out.

This work has been carried out on post-mortem brain samples and on cell cultures. The next step will be to analyze the glycosylation of the app fragments in the cerebrospinal fluid. "Right now we have a new tool that can be used in the short term for biochemical diagnosis of Alzheimer's patients in the laboratory," concludes Dr. Sáez-Valero.

Credit: 
Spanish National Research Council (CSIC)

Buffalo-based study aims to connect the dots on food access

BUFFALO, N.Y. -- Researchers know from many previous studies what prevents cash-strapped shoppers in underserved communities from buying more fresh produce. But little is known about which strategies are most likely to reach the people who need them, or have the most success in improving the diets of people in lower income areas.

A new University at Buffalo study based in Western New York is the first that simultaneously examined the preferences of community members and compared those with the community-based programs and resources available to identify the most viable strategies for addressing disparities in healthy food consumption.

Previous research has shown that only 12% and 7% of adults living at or below the poverty line meet fruit and vegetable recommendations, respectively.

"We continue to find that cost, food preferences, availability, access and limited food assistance eligibility and/or benefits are persistent barriers. Residents of underserved communities feel that increasing the affordability of fruits and vegetables through incentives, nutrition education, and increased access to healthy food options will help them to eat more fruits and vegetables," said Christina Kasprzak, lead author on the study published in the Journal of Hunger & Environmental Nutrition.

"We also found that healthy food incentives, mobile produce markets, and nutrition education are acceptable and preferred food access strategies," added Kasprzak, a PhD candidate in community health and health behavior in UB's School of Public Health and Health Professions.

Researchers conducted 13 focus groups with 98 lower-income participants in urban areas of Western New York. Eight of the focus groups were conducted at local Women, Infant and Children (WIC) offices, while the remaining five were recruited by community organizations that serve lower-income families. The research team also interviewed 17 grocery store owners or managers, farmers, food distributors, and representatives from community organizations that currently or would be willing to address food access issues.

How to match needs

"Our research evaluated the capacity among local stakeholders to address the needs of lower-income communities, and made recommendations of how we can match this capacity to the preferences voiced in the focus groups with lower-income individuals," Kasprzak said.

"By capitalizing on where there are matches between lower-income communities' preferences and stakeholders we can ensure our efforts to expand healthy food access are viable," Kasprzak said. "We don't necessarily need to completely abandon the mismatches between programs and preferences, but we should heed community members' suggestions for these programs and avoid blindly establishing programs that may not be fruitful."

Cost, limited availability and accessibility, taste preferences and limited federal nutrition eligibility and benefits were the most frequently mentioned barriers to fruit and vegetable consumption. Study participants expressed frustration with having to decide between buying fresh produce and less healthy food options because of cost differences.

Another recurring theme among study participants was that they said they often had to travel outside their neighborhood, which required transportation, to find affordable and high-quality produce.

Researchers also reported that twice as many participants felt they lacked access to healthy food as those who said they had access.

What did participants say would help them buy and eat more fresh foods? Increasing the affordability, as well as nutrition education and recipe ideas. Some participants expressed a desire to learn healthier ways to prepare foods unique to their culture.

Include the working poor

Many participants favored increasing federal nutrition program benefits -- such as Supplemental Nutrition Assistance Program (SNAP) -- or expanding the eligibility requirements for these programs to include the working poor.

On the retail side, store owners and managers interviewed said they'd be willing to expand their fresh produce offerings to meet customers' demands, while supporting efforts to improve the health of the community.

For corner stores -- whose prices generally are known to be higher -- owners wanted guidance on what to stock, how to price and promote those items, and where to source fruits and vegetables.

Farmers expressed a willingness to accept SNAP benefits for Community Supported Agriculture (CSA) shares, and to provide produce to urban corner stores.

Kasprzak was pleasantly surprised to learn that there is ample opportunity for local stakeholders to help lower-income communities access and eat more fruits and vegetables.

"By connecting the dots, we can potentially enhance the reach of existing programs that are preferred by these communities," she said.

Ultimately, though, the barriers of cost of fruits and vegetables and limited eligibility and benefits for nutrition assistance programs are not wholly addressed by the food access programs discussed in the research paper, Kasprzak notes.

"For example, an incentive program makes fruits and vegetables more affordable but does not directly drive down the cost of produce. Therefore, more concerted efforts at the state or national level are needed."

"We know that many of the programs that community members would like to see already exist, but budget and expertise to market these programs are often lacking in small organizations," added Lucia Leone, PhD, the senior author on the paper and an assistant professor of community health and health behavior at UB. "Support from local policy makers is crucial for both getting the word out about these programs and ensuring their sustainability."

Credit: 
University at Buffalo

Stroke patients with COVID-19 have increased inflammation, stroke severity and death

image: Stroke patients who also have COVID-19 showed increased systemic inflammation, a more serious stroke severity and a much higher rate of death, compared to stroke patients who did not have COVID-19, according a retrospective, observational, cross-sectional study of 60 ischemic stroke patients admitted to UAB Hospital between late March and early May 2020.

Image: 
UAB

BIRMINGHAM, Ala. - Stroke patients who also have COVID-19 showed increased systemic inflammation, a more serious stroke severity and a much higher rate of death, compared to stroke patients who did not have COVID-19, according to University of Alabama at Birmingham research led by Chen Lin, M.D., an assistant professor in the UAB Department of Neurology.

The research, published in the journal Brain, Behavior & Immunity - Health, is a retrospective, observational, cross-sectional study of 60 ischemic stroke patients admitted to UAB Hospital between late March and early May 2020. Ischemic stroke occurs when a blood vessel for the brain is blocked by a clot, depriving some brain tissue of oxygen. All patients were tested for COVID-19 at admission.

The UAB researchers mined electronic medical records of confirmed stroke cases for information on age, gender and race; clinical variables; laboratory data, including complete blood counts, blood chemistry and coagulation tests; and outcomes, including death, length of hospital stay and condition at discharge.

The ratio of the number of neutrophils to the number of lymphocytes, or the NLR, as calculated from blood count data, served as an index of the systemic inflammatory response. While other researchers have associated NLR with COVID-19 disease severity, refractory disease and even as an independent factor for mortality, "our study is the first to associate the NLR in patients with COVID-19 and ischemic stroke and stroke severity," Lin said.

Of the 60 hospitalized patients with acute systemic stroke, nine were positive for a COVID-19 infection.

The UAB research had four major findings. First, patients who were positive for COVID-19 presented with a more severe neurological deficit at admission, as measured by the National Institutes of Health Stroke Scale, or NIHSS, score, which averaged 18.4. Second, all patients with an NIHSS score higher than 4 -- including uninfected patients -- had a significantly higher NLR than those with lower scores. The NIHSS is used to predict lesion size and gauge stroke severity.

Third, patients with COVID-19 had an increased inflammatory response, including significantly higher neutrophil counts, lower lymphocyte counts and an increased NLR, compared with uninfected patients. Finally, stroke patients with COVID-19 had a significantly higher mortality
rate -- 44.4 percent, versus 7.6 percent for uninfected stroke patients.

Two other studies this year have reported clinical and laboratory differences in ischemic stroke patients with and without COVID-19, Lin says, but neither addressed racial differences or NLR differences between groups.

"We have reported the first experience within the 'Stroke Belt' of the Southern United States, which has the highest proportion of African American stroke patients," said Lin, who is also the director of the Stroke Recovery Clinic in the UAB Division of Cerebrovascular Disease. In the UAB study, African Americans comprised 55.6 percent of those who had COVID-19 and stroke and 37.7 percent of those with only stroke.

"Interestingly, in our patients with stroke and COVID-19, the neutrophil and lymphocyte levels were only borderline high and low, respectively," Lin said, "yet the NLR was almost twice as high as in patients without COVID-19. This potentially indicates that the systemic inflammatory response triggered by COVID-19 can cascade from multiple components."

Credit: 
University of Alabama at Birmingham