UT Southwestern Medical Center Diffusion tractography uses the movement of water molecules to identify tracts that connect different parts of the brain. It can be used to pinpoint the part of the thalamus to treat with focused ultrasound. DALLAS – June 14, 2020 – Recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson’s disease and essential tremor may lead to better outcomes without surgery and with less risk of negative effects, a new study led by UT Southwestern researchers suggests. The study, published today in Brain, describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain’s thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern’s Peter O’Donnell Jr. Brain Institute. “The benefit for patients is that we will be better able to target the brain structures that we want,” Shah says. “And because we’re not hitting the wrong target, we’ll have fewer adverse effects.” The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall. Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah. According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson’s disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study. In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack. About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson’s disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. “No cuts. No anesthesia. No implanted devices.” A challenge in both procedures has been locating the precise area inside the brain’s thalamus to treat – the pea-sized ventral intermediate nucleus, says Dr. Shah. Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target. Three newly refined MRI techniques are better at delineating the target tissue, according to the study. The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues. The other methods described are quantitative susceptibility mapping – which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood – and fast gray matter acquisition TI inversion recovery – which operates much like a photo negative, turning the brain’s white matter dark and its gray matter white in order to provide greater detail in the gray matter. Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients. Senior author of the study was Rajiv Chopra, Ph.D., director of image-guided therapy development and associate professor of radiology in the Advanced Imaging Research Center at UTSW. Researchers at the Mayo Clinic also participated in the study.
ATS Drug shortages exacerbated by COVID-19. Newswise — June 11, 2020─ A new paper published online in the Annals of the American Thoracic Society examines the nation’s current shortage of vitally needed medications, and how this dangerous situation is being made worse by the COVID-19 pandemic. The authors provide recommendations on how clinicians and institutions might address potential scarcities of essential medications during the current public health crisis. In “Preparing for COVID-19 Related Drug Shortages,” Andrew G. Shuman, MD, and co-authors discuss how the federal and state governments, as well as health care providers, need to develop ethically sound policies that address already perilously low supplies of certain commonly-used medications, which are dwindling further due to resources needed to combat COVID-19. “It is critical that these conversations occur now due to current shortages, as well as the necessary lead time to plan for future shortages,” said Dr. Shuman, co-chief of the Clinical Ethics Service, Center for Bioethics and Social Sciences in Medicine, University of Michigan Medical School. “Drug shortages have been a national emergency for years and are currently exacerbated due to COVID-19. Issues related to supply chain and anticipated increased ICU needs over the course of the pandemic are worsening the problem.” Yoram Unguru, MD, MS, MA, a physician-ethicist at The Herman and Walter Samuelson Children’s Hospital at Sinai and Johns Hopkins Berman Institute of Bioethics, who is a co-author of the paper, added, “As of today the American Society of Health-system Pharmacists (ASHP) reports 213 drugs shortages in the United States. It is not just patients with COVID-19 who are affected. One example of a current drug with a critically short supply is Erwinia asparaginase, a life-saving chemotherapeutic agent for both children and adults with cancer.” Among medical specialties severely affected are oncology, critical care and infectious disease. The authors stated that regional communication among hospitals is an important first step — helping determine how local drug supply chains are affected — and that coordination and sharing mechanisms are also critical. This information sharing would ideally occur via a central repository or clearinghouse. Both the FDA and ASHP also maintain databases of current drug shortages, and independent health care companies maintain their own databases that can provide invaluable information. “Sharing information is an important first step,” the authors stated. “The second and more difficult step involves actual sharing of medications among hospitals and health systems.” There are a number of barriers to this taking place, among others, the need for cooperation among competing health systems, concerns about potential liability, and legal regulations that affect the transfer of drugs. Erin Fox, PharmD, a co-author who is director of drug information and support services for Utah Health noted, “Tantamount to this effort is facilitating communication between pharmacists — those tasked with maintaining supplies, as well as those embedded within clinical teams — in order to inform the clinical team how supply may impact care delivery.” She continued, “Pandemic-era strategies for conservation of commonly used critical care agents at risk of shortages should be noted, recognizing that these shortages are often regional and unpredictable, and intensive care protocols and strategies are highly individualized.” A list of these commonly used drugs is included in the paper. The authors noted that communication should not be limited to discussions among pharmacists, hospitals, and health systems. Open discussions with patients who are most affected by drug shortages are essential. In the spirit of openness, the authors recommended that hospitals consider publicly posting information about drug shortages. Dr. Shuman and colleagues called upon stakeholders, from governments to clinicians, to refocus some of their efforts in managing shortages of ventilators during the COVID-19 crisis to develop workflows and rationing criteria for essential medicines. “Even if there are sufficient ventilators, a critical shortage of sedatives, paralytics and/or opioids will obviate the ability to keep patients safely intubated. Data suggest that these shortages have already been associated with inadvertent extubations.” The authors have also identified hoarding of drugs thought to be potential COVID treatments as a problem. “Once effective treatments and/or vaccines for COVID-19 are available, prioritizing nascent supplies will present a formidable challenge,” they predicted. “In the coming days and months, this matter demands global attention. Only with clear lines of communication and a proactive, collaborative approach can we weather this impending storm.”
Newswise — Population-wide use of facemasks keeps the coronavirus ‘reproduction number’ under 1.0, and prevents further waves of the virus when combined with lockdowns, a modelling study from the universities of Cambridge and Greenwich suggests. The research suggests that lockdowns alone will not stop the resurgence of SARS-CoV-2, and that even homemade masks with limited effectiveness can dramatically reduce transmission rates if worn by enough people, regardless of whether they show symptoms. The researchers call for information campaigns across wealthy and developing nations alike that appeal to our altruistic side: “my facemask protects you, your facemask protects me”. The findings are published in the Proceedings of the Royal Society A. “Our analyses support the immediate and universal adoption of facemasks by the public,” said lead author, Dr Richard Stutt, part of a team that usually models the spread of crop diseases at Cambridge’s Department of Plant Sciences. “If widespread facemask use by the public is combined with physical distancing and some lockdown, it may offer an acceptable way of managing the pandemic and re-opening economic activity long before there is a working vaccine.” Dr Renata Retkute, coauthor and Cambridge team member, said: “The UK government can help by issuing clear instructions on how to make and safely use homemade masks.” “We have little to lose from the widespread adoption of facemasks, but the gains could be significant.” The new coronavirus is transmitted through airborne droplets loaded with SARS-CoV-2 particles that get exhaled by infectious people, particularly when talking, coughing or sneezing. For the latest study, Cambridge researchers worked to link the dynamics of spread between individuals with population-level models, to assess different scenarios of facemask adoption combined with periods of lockdown. The modelling included stages of infection and transmission via surfaces as well as air. Researchers also considered negative aspects of mask use, such as increased face touching. The reproduction or ‘R’ number – the number of people an infected individual passes the virus onto – needs to stay below 1.0 for the pandemic to slow. The study found that if people wear masks whenever they are in public it is twice as effective at reducing ‘R’ than if masks are only worn after symptoms appear. In all modelling scenarios, routine facemask use by 50% or more of the population reduced COVID-19 spread to an R less than 1.0, flattening future disease waves and allowing less-stringent lockdowns. Viral spread reduced further as more people adopted masks when in public. 100% mask adoption combined with on/off lockdowns prevented any further disease resurgence for the 18 months required for a possible vaccine. The models suggest that – while the sooner the better – a policy of total facemask adoption can still prevent a second wave even if it isn’t instigated until 120 days after an epidemic begins (defined as the first 100 cases). The team investigated the varying effectiveness of facemasks. Previous research shows that even homemade masks made from cotton t-shirts or dishcloths can prove 90% effective at preventing transmission. The study suggests that an entire population wearing masks of just 75% effectiveness can bring a very high ‘R’ number of 4.0 – the UK was close to this before lockdown – all the way down to under 1.0, even without aid of lockdowns. In fact, masks that only capture a mere 50% of exhaled droplets would still provide a “population-level benefit”, even if they quadrupled the wearer’s own contamination risk through frequent face touching and mask adjustment (a highly unlikely scenario). The researchers point out that crude homemade masks primarily reduce disease spread by catching the wearer’s own virus particles, breathed directly into fabric, whereas inhaled air is often sucked in around the exposed sides of the mask. “There is a common perception that wearing a facemask means you consider others a danger,” said Professor John Colvin, coauthor from the University of Greenwich. “In fact, by wearing a mask you are primarily protecting others from yourself.” “Cultural and even political issues may stop people wearing facemasks, so the message needs to be clear: my mask protects you, your mask protects me.” “In the UK, the approach to facemasks should go further than just public transport. The most effective way to restart daily life is to encourage everyone to wear some kind of mask whenever they are in public,” Colvin said. Prof Chris Gilligan, coauthor from Cambridge’s Epidemiology and Modelling Group in the Department of Plant Sciences, added: “These messages will be vital if the disease takes hold in the developing world, where large numbers of people are resource poor, but homemade masks are a cheap and effective technology.”
Newswise — The country’s first convalescent plasma transfusion trial results have been peer-reviewed and published, showing 19 out of 25 patients improving with the treatment and 11 discharged from the hospital. On March 28, Houston Methodist became the first academic medical center in the nation to transfuse plasma from recovered COVID-19 patients into two critically ill patients. With no adverse side effects caused by the plasma transfusion, the study concluded that convalescent plasma is a safe treatment option for patients with severe COVID-19 disease. To date, this is the largest cohort worldwide assessed for outcomes pertaining to convalescent plasma transfusion for COVID-19. The findings are described in a paper appearing in press May 26 (online May 28) in The American Journal of Pathology. This is the first peer-reviewed publication on convalescent plasma use in the U.S. James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, is the corresponding author on the study, titled “Treatment of COVID-19 patients with convalescent plasma.” Eric Salazar, M.D., Ph.D., assistant professor of pathology and genomic medicine with the Houston Methodist Research Institute, is the principal investigator who led the project to treat critically ill COVID-19 patients with convalescent plasma. “While physician scientists around the world scrambled to test new drugs and treatments against the COVID-19 virus, convalescent serum therapy emerged as potentially one of the most promising strategies,” Musser said. “With no proven treatments or cures for COVID-19 patients, now was the time in our history to move ahead rapidly.” Patients were first treated under emergency use guidelines (eIND) from the U.S. Food and Drug Administration and then received approval April 3 from the FDA to open up the trial to more patients as an investigational new drug (IND). This extraordinarily rapid approval granted by the FDA opened up access to convalescent plasma treatment for COVID-19 patients. The century-old therapeutic approach dates back to at least as early as 1918 to fight the Spanish Flu and more recently was used with some success during the 2003 SARS pandemic, the 2009 influenza H1N1 pandemic and the 2015 Ebola outbreak in Africa. Following a study early on in the COVID-19 pandemic, where a handful of critically ill patients in China showed improvement, an interdisciplinary team of Houston Methodist physician scientists and health care workers rapidly targeted the COVID-19 virus with convalescent serum therapy. Additional findings during this trial revealed patient outcomes following plasma therapy were very similar to recently published results of patients treated on a compassionate-use basis with the antiviral drug remdesivir. The research team also concluded that any observed complications were consistent with findings reported for COVID-19 disease progression and did not result from the plasma transfusions. The study’s overall findings were consistent with several other small case studies of convalescent plasma use for severe COVID-19 that have been recently reported. Ultimately, although the convalescent plasma therapy administered on the front lines at Houston Methodist was implemented for emergency treatment, the study’s authors recognize the important need for controlled clinical trials to determine its therapeutic efficacy. A randomized controlled trial is currently being considered at Houston Methodist where they would also look more closely at variables such as timing of the transfusion after the onset of symptoms, the number and volume of transfusions adjusted for patient biometrics, antibody levels in donor plasma and numerous other parameters needed to effectively evaluate how to optimize this therapy. This would help address some questions, including whether patients would have better outcomes if plasma transfusions were administered sooner after the onset of symptoms. Not all plasma recipients transfused so far at Houston Methodist were part of this first trial. Since late March, when the first patients were infused with convalescent plasma, Houston Methodist has treated 74 critically ill COVID-19 patients, 50 of whom have been discharged from the hospital and are recovering. More than 150 recovered COVID-19-infected individuals donated their plasma, many of them continuing to do so frequently. AJP, an Elsevier journal, is the official journal of the American Society for Investigative Pathology and publishes high-quality original research reports, reviews and commentaries related to the molecular and cellular basis of disease. In addition to Musser and Salazar, other collaborators on this study were Katherine K. Perez, Madiha Ashraf, Jian Chen, Brian Castillo, Paul C. Christensen, Taryn Eubank, David W. Bernard, Todd Eagar, S. Wesley Long, Sishir Subedi, Randall J. Olsen, Christopher Leveque, Mary R. Schwartz, Monisha Dey, Cheryl Chavez-East, John Rogers, Ahmed Shehabeldin, David Joseph, Guy Williams, Karen Thomas, Faisal Masud, Christina Talley, Katharine G. Dlouhy, Bevin Lopez, Curt Hampton, Jason Lavinder, Jimmy D. Gollihar, Andre C. Maranhao, Gregory C. Ippolito, Matthew Ojeda Saavedra, Concepcion C. Cantu, Prasanti Yerramilli and Layne Pruitt. This study was supported by funding from the National Institutes of Health (grants AI146771-01 and AI139369-01), the Fondren Foundation, the National Institute of Allergy and Infectious Diseases (Contract Number 75N93019C00050), the Army Research Office (Cooperative Agreement W911NF-12-1-0390), Houston Methodist Infectious Diseases Research Fund, Houston Methodist Hospital and Houston Methodist Research Institute. Photo: Houston Methodist Houston Methodist physician scientists (left to right) Eric Salazar, MD, PhD, and James M. Musser, MD, PhD, discuss their convalescent plasma trial for treating COVID-19, the results of which were the first in the U.S. to be peer-reviewed and published.
Newswise — LA JOLLA—Every year, more than 68,000 people end up with a clinical case of Japanese encephalitis. One in four of these patients will die. The mosquito-borne virus, which is most common in Southeast Asia, also causes severe neurological damage and psychiatric disorders. There is no cure for Japanese encephalitis, but there are effective vaccines against Japanese encephalitis virus (JEV). The problem is that JEV’s range is spreading, and more and more people at risk of the disease also live in areas where viruses like Zika are prevalent. In a new study, published June 5, 2020, in the Journal of Experimental Medicine, scientists at La Jolla Institute for Immunology (LJI) shows that antibodies against JEV are “cross-reactive” and can also recognize Zika virus. Unfortunately, these antibodies can actually make Zika cases more severe. The research, conducted in mice, is the first to show that T cells can counteract this dangerous phenomenon. “This means we probably need to be developing a vaccine against both viruses that can elicit a good balance of antibodies and T cells,” says Associate Professor Sujan Shresta, Ph.D., who co-led the study in collaboration with Jinsheng Wen, Ph.D., of Ningbo University and Wenzhou Medical University, and Yanjun Zhang, Ph.D., of Zhejiang Provincial Center for Disease Control and Prevention. Shresta has spent much of her career studying flaviruses, a family of viruses which includes Zika, JEV, dengue, West Nile virus and yellow fever. These diseases have spread in recent years as more people around the world have moved to cities and climate change has allowed the mosquitoes that carry these diseases to expand their habitat. People in many countries now live at risk of encountering multiple harmful flaviviruses in their lives. “The immune responses to these viruses are very cross-reactive,” says Shresta. “The problem is that the immune response can be both good and bad.” In some cases, antibodies against one flavivirus can make a future flavivirus infection even worse by allowing the virus to enter host cells. Shresta and investigators worldwide have shown this process, called antibody-dependent enhancement (ADE), during Zika and dengue infections in animal models that recapitulate severe dengue or Zika disease in individuals with prior exposure to dengue or Zika virus. However, ADE of Zika disease in cases of previous JEV exposure, and the interplay between antibodies and infection-fighting immune cells called CD8+ T cells, had not been studied before. For the new study, Shresta and her colleagues took antibodies from JEV-infected mice or JEV-vaccinated people and injected them into healthy mice. The healthy mice were then exposed to Zika virus. These mice experienced ADE and had far more severe cases of Zika fever than mice with no antibodies against JEV. Shresta and her colleagues next focused their attention on CD8+ T cells from JEV-infected mice. They found that CD8+ T cells primed to fight JEV could counteract the harmful effects of cross-reactive antibodies. “These JEV-elicited T cells were indeed able to recognize and get rid of the Zika virus infection,” says Shresta. In short, the mouse survival rate went up and their viral load went down, thanks to the CD8+ T cells. A future JEV vaccine would need to prompt a similar response from CD8+ T cells to help a person avoid ADE of Zika infection. Shresta says this work can help shed light on how to fight the whole family of flaviviruses, which includes over 70 different species, and many countries are increasingly dealing with cocirculation of multiple flaviviruses. “Any of these viruses could cause a major, major outbreak,” says Shresta. “We need to look at deploying a combination Zika/JEV vaccine, and we may need to tailor vaccines to particular locations where we know both JEV and Zika pose a threat.” Shresta adds that research into cross-reactive antibodies and T cell responses is especially important today as scientists investigate whether exposure to common cold coronaviruses can leave a person with any immunity against SARS-CoV-2, the novel coronavirus. “This provides us with a really good model to learn about immune response,” Shresta says. The study, titled, “Japanese encephalitis virus-primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis,” was supported by the K.C. Wong Magna Fund of Ningbo University, the Zhejiang Provincial Natural Science Foundation (LY17C010004), the National Natural Science Foundation of China (31870159) and institutional funds from the La Jolla Institute for Immunology. Additional authors included Zhiliang Duan, Wenhua Zhou, Weiwei Zou, Shengwei Jin, Dezhou Li, Xinyu Chen, Yongchao Zhou, Lan Yang and Yanjun Zhang. DOI: 10.1084/jem.20192152
Newswise — Hamilton, ON (June 1, 2020) – A comprehensive review of existing evidence supports physical distancing of two metres or more to prevent person-to-person transmission of COVID-19, says an international team led by McMaster University and St. Joseph’s Healthcare Hamilton. Face masks and eye protection decrease the risk of infection, too. The systematic review and meta-analysis was commissioned by the World Health Organization. The findings were published today in The Lancet. “Physical distancing likely results in a large reduction of COVID-19,” said lead author Holger Schünemann, professor of the departments of health research methods, evidence, and impact, and medicine at McMaster. Schünemann is co-director of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations. He also is director of Cochrane Canada and McMaster GRADE Centre. “Although the direct evidence is limited, the use of masks in the community provides protection, and possibly N95 or similar respirators worn by health-care workers suggest greater protection than other face masks,” Schünemann said. “Availability and feasibility and other contextual factors will probably influence recommendations that organizations develop about their use. Eye protection may provide additional benefits.” The systematic review was conducted by a large, international collaborative of researchers, front-line and specialist clinicians, epidemiologists, patients, public health and health policy experts of published and unpublished literature in any language. They sought direct evidence on COVID-19 and indirect evidence on related coronaviruses causative of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The team used Cochrane methods and the Grading of Recommendations, Assessment, and Evaluation (GRADE) approach which is used world-wide to assess the certainty of evidence. They identified no randomized control trials addressing the three coronaviruses but 44 relevant comparative studies in health-care and non-health-care (community) settings across 16 countries and six continents from inception to early May 2020. The authors noted more global, collaborative, well-conducted studies of different personal protective strategies are needed. For masks, large randomized trials are underway and are urgently needed. The scientific lead is Derek Chu, a clinician scientist in the departments of health research methods, evidence, and impact, and medicine at McMaster and an affiliate of the Research Institute of St. Joe's Hamilton. “There is an urgent need for all caregivers in health-care settings and non-health-care settings to have equitable access to these simple personal protective measures, which means scaling up production and consideration about repurposing manufacturing,” said Chu. “However, although distancing, face masks, and eye protection were each highly protective, none made individuals totally impervious from infection and so, basic measures such as hand hygiene are also essential to curtail the current COVID-19 pandemic and future waves.” The work was funded by the World Health Organization and involved close collaboration with the American University of Beirut, Lebanon and many international partners. Photo credit: by Gerli Sirk Caption: Holger Schünemann is a professor of the departments of health research methods, evidence, and impact, and medicine at McMaster. He is also co-director of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations.
Tokyo, Jun 1, 2020 A team of scientists from Japan recently achieved more efficient degradation of the human serum albumin protein—an important protein in the blood—via high-intensity infrared irradiation, by attaching a zinc metal complex to the protein. Their findings indicate potential for future application of certain metal complexes to therapeutic interventions for diseases such as Alzheimer’s. Artificial metalloenzymes are hybrid compounds that are synthesized by attaching metal complexes to protein molecules. In the past few years, these compounds have garnered considerable attention in research communities because of their applicability as bio-inspired catalysts, in biofuel cells, and in therapeutic interventions such as targeted protein degradation and drug delivery. Advancing research on their application in targeted protein degradation, a team of scientists from the Tokyo University of Science, Japan, and Universidad Complutense de Madrid, Spain, examined the degradation of a specific metalloenzyme upon irradiation with high-energy infrared radiation. This metalloenzyme was one they had created by attaching a zinc metal complex (ZnL) to human serum albumin (HSA). The use of high-energy infrared radiation to degrade proteins is not new. For instance, a previous study at the Tokyo University of Science used this technique to degrade several protein aggregates, including the protein aggregate whose buildup between neurons in the brain, called amyloid plaque, causes Alzheimer’s disease. What the present study finds, as Dr Takashiro Akitsu, lead scientist, explains, is that “when human serum albumin is conjugated with a zinc complex, protein damage is promoted upon irradiation with a mid-infrared free-electron laser.” A mid-infrared free-electron laser (IR-FEL) is the instrument that the scientists used to irradiate the hybrid. The team of scientists comprising Prof Akitsu, Prof Koichi Tsukiyama, Dr Takayasu Kawasaki, and Assistant Prof Tomoyuki Haraguchi, among others, from Japan and Prof Mauricio A. Palafox from Complutense de Madrid, Spain, first used infrared (IR) spectroscopy to verify the attachment of ZnL to HSA. The IR spectra they obtained also indicated the optimal wavelengths for degradation: these were 1537, 1652, and 1622 cm-1, corresponding to the two amide bonds in HSA and the carbon-nitrogen double bond of ZnL, respectively. The scientists created thin films of both the HSA and the HSA+ZnL hybrid and irradiated targeted portions of these films. They then compared the radiation damage caused by IR-FEL irradiation to the films, using a technique called Fourier transform infrared (FT-IR) microscopy and a program to evaluate changes in the protein secondary structure, called IR-SSE. At 1622 cm-1, the HSA+ZnL hybrid structure did not dissociate. But, at the other two wavelengths, the protein structure of HSA, in both the pure HSA and hybrid forms, appeared significantly damaged. Further, in the latter cases, the hybrid compound was more degraded than pure HSA was. The scientists believe that the attachment of ZnL to the HSA protein destabilized the protein structure, allowing it to degrade more easily. Overall, this attachment of ZnL was feasible and assisted the degradation of the protein instead of alleviating it. These results are presented in a paper published in the International Journal of Molecular Sciences, in which the scientists highlight that “at present, the exact binding mechanism between the complex and the protein is unknown.” Further, Prof Akitsu clarifies that “research on various protein-metal complex pairs is ongoing.” The findings of this study cannot yet be generalized and until scientists have better insights, the applications of such metal complex-protein hybrids in therapeutic interventions or other areas of biotechnology will remain limited. Nevertheless, this study, in addition to the previous studies conducted at the Tokyo University of Science in this field, certainly makes us hopeful of a future in which diseases that involve protein defects, such as Alzheimer’s, are curable. *** Reference Title of original paper: Degradation of Human Serum Albumin by Infrared Free Electron Laser Enhanced by Inclusion of a Salen-Type Schiff Base Zn (II) Complex Journal: International Journal of Molecular Sciences DOI: 10.3390/ijms21030874 About the Tokyo University of Science Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators. With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field. Website: https://www.tus.ac.jp/en/mediarelations/ About Prof Takashiro Akitsu from the Tokyo University of Science Takashiro Akitsu is a Professor at the Faculty of Science at Tokyo University of Science. As an active researcher in the field of inorganic chemistry, he focuses particularly on coordination chemistry and materials science. He has a PhD from Osaka University, having focused his post-graduate research on coordination, crystal and bioinorganic chemistry. He was named Professor of the Year in 2018 for his teaching work on biomaterials, and holds a patent for an ultraviolet absorber since 2016. Funding information This research was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology, under the Photon Beam Platform Project.
Coriell Life Sciences’ advanced data analytics examine individuals’ health history to identify those who are more likely to have severe or fatal outcomes if infected with novel coronavirus. Newswise — As more businesses and employees prepare to return to work around the country, Coriell Life Sciences (CLS) is rolling out a new tool in the fight against COVID-19: personalized COVID-19 Risk Scores. Using proprietary, advanced data analytics, CLS analyzes information from medical records to identify the number of unique risk factors linked to poor COVID-19 outcomes an individual has. Factors include thousands of potential risk elevators, from cardiovascular disease, diabetes and hypertension to allergies, anemia, and more. The higher the number of risk factors, the higher the likelihood of experiencing severe or fatal symptoms if infected with the virus. “This type of intelligence has the power to play a pivotal role in protecting the most vulnerable among us,” says Jeffrey A. Shaman, PhD, Chief Science Officer at Coriell Life Sciences. “It’s clear people who suffer from chronic medical conditions are far more likely to fare poorly if they have COVID-19, but it’s hardly that simple. Other factors, such as blood type and medications used, are also showing evidence they may be related to negative outcomes. By analyzing individuals’ health history against thousands of medical codes that are aligned to risk factors for poor COVID-19 outcomes, we can determine who has the greatest risk of requiring acute care and empower them to be more vigilant in protecting their health.” Individuals are eligible for COVID-19 risk scoring through participating employers. “Beyond empowering individuals to better protect their health, this information can also be used to help business leaders strategically tackle the high-stakes complexities surrounding when and how to get their teams back to work safely,” notes Coriell Life Sciences’ President & CEO Scott Megill. “Both are critical elements in lessening the impact of this pandemic on public health and our country’s economic health. The bottom line is we must make better use of the information that’s available today while the global scientific community remains keenly focused on scaling diagnostics and developing effective therapeutics and a viable vaccine.” COVID-19 risk scoring is part of CLS’ new Return to Work Program. This program provides an intelligence-driven solution designed to help organizations safely resume operations. In addition to analyzing employee and facility data to illuminate risks and barriers to re-opening, the program offers businesses turnkey infrastructure for managing large-scale COVID-19 testing of employees in partnership with a network of laboratories across the country. A leader in genetic science, CLS also enables organizations to help employees advocate for their health by offering personalized COVID-19 Genetic Drug Safety Reports. Based on preemptive DNA testing, this report reveals how an individual would likely respond to approximately 45 drugs that could be used during COVID-19 treatment and have known genetic implications. This information can be provided to a physician or pharmacist to inform an effective treatment plan. “The reality is that some drugs just don’t work for some people,” notes Dr. Shaman. “Some aren’t safe for one person but are completely fine for another. Differences in our DNA are responsible for some of this variation. Precision medicine enables us to determine which drugs will be both safe and effective for patients with COVID-19 – as well as many other conditions.” To learn more, visit coriell.com. About Coriell Life Sciences Coriell Life Sciences (CLS), a leader in genetic science, uses innovation in precision medicine to reduce healthcare costs and empower a healthier world. With scientific expertise that spans six decades, CLS bridges the gap between genetic knowledge and clinical application and offers the most comprehensive medication risk management program on the market. Visit coriell.com, email email@example.com or follow @CoriellLife.
Renowned program led by James M. Wilson, MD, PhD, a leading expert in the technology platform used in the experimental vaccine, to conduct preclinical studies in joint research and development project with Massachusetts Eye and Ear and Massachusetts General Hospital. Newswise — The internationally-renowned Gene Therapy Program at the University of Pennsylvania is joining the AAVCOVID vaccine program led by Massachusetts Eye and Ear and Massachusetts General Hospital (MGH), members of Mass General Brigham for the joint research program. AAVCOVID is a unique gene-based vaccine candidate designed to protect against SARS-CoV-2, the virus that causes COVID-19. The AAVCOVID vaccine program was developed in the laboratory of Luk H. Vandenberghe, PhD, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear and Associate Professor of Ophthalmology at Harvard Medical School. AAVCOVID is a prophylactic gene-based immunization approach that uses an adeno-associated virus (AAV) vector to deliver and express gene fragments of SARS-CoV-2 virus to the body to elicit a protective immune response. The AAVCOVID vaccine is currently in preclinical development with a plan to begin clinical testing in humans later this year. Mason Freeman, MD, director and founder of the MGH Translational Research Center and a Professor of Medicine at Harvard Medical School, is leading the efforts to develop the clinical studies intended to establish safety and efficacy of the experimental vaccine. The AAVCOVID vaccine program will greatly benefit from the participation of Penn Medicine’s Gene Therapy Program, led by gene transfer pioneer James M. Wilson, MD, PhD, as the Gene Therapy Program’s involvement will enable the experimental vaccine to undergo additional rounds of critical preclinical studies that are required for the U.S. Food and Drug Administration investigational new drug (IND) application process. “We are leveraging the enormous clinical experience of AAV for gene therapy in this vaccine application. The capsid selected for this project was discovered when Luk was a graduate student in my lab. It has the unique properties of activating immune responses, which is important for its use as a genetic vaccine, rather than suppressing immune responses which characterizes most capsids used for gene therapy. I am absolutely delighted to team up with Luk and Mason for this important project.” says Dr. Wilson, who is the Rose H. Weiss Professor and Director of the Orphan Disease Center, and Professor of Medicine and Pediatrics at Penn’s Perelman School of Medicine. Under the direction of Dr. Wilson, the Gene Therapy Program currently employs over 280 full-time employees with operations supported by a diverse group of public and private sponsors. “Dr. Wilson and his lab have made seminal contributions to the field of gene transfer for vaccines and therapy. The expertise and speed in pre-clinical development from this world-leading team joining the AAVCOVID project is a tremendous gain towards our ultimate goal of getting a vaccine into the clinic,” says Dr. Vandenberghe. “We are grateful to the Gene Therapy Program at Penn Medicine and our collaborators in academia and industry for their shared commitment to battling the coronavirus pandemics.” About AAVCOVID Vaccine Program The AAVCOVID vaccine program is a gene-based vaccine strategy that seeks to deliver genetic sequences of the SARS-CoV-2 using an AAV vector. Vaccination delivers genetic DNA fragments from SARS-CoV-2 which generates an antigen protein, which is designed to elicit an immune response to prevent infection. This approach is supported by extensive data demonstrating safety of the AAV technology platform in other diseases, including two FDA-approved medications. The AAVCOVID project collaboration is led by principal investigator Dr. Vandenberghe, the Grousbeck Family Chair in Gene Therapy at Mass. Eye and Ear, who is a world-renowned leader and pioneer of viral gene transfer and therapeutic gene transfer. Dr. Vandenberghe and his laboratory began work on the vaccine in mid-January following the Wuhan outbreak and the first publication of genetic sequences of the new coronavirus. Using a specific AAV with desirable vaccine properties, the program seeks to induce immunity to prevent infection and disease in healthy populations, leveraging the existing manufacturing capabilities of the AAV industry. Dr. Vandenberghe is working in conjunction with Dr. Freeman at MGH, who serves as Director of the Translational Medicine Group of the MGH Center for Computational and Integrative Biology and is Professor of Medicine at Harvard Medical School. The project aims to enter clinical trials in the second half of 2020. AAV is also a rapidly adaptable technology. If a new strain of the SARS-CoV-2 virus emerges, the genetic code inside the AAVCOVID vaccine could be exchanged for an updated genetic code and processed into a new vaccine in weeks, according to the researchers. About Massachusetts Eye and Ear Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. A member of Mass General Brigham, Mass. Eye and Ear specializes in ophthalmology (eye care) and otolaryngology–head and neck surgery (ear, nose and throat care). Mass. Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass. Eye and Ear scientists are driven by a mission to discover the basic biology underlying conditions affecting the eyes, ears, nose, throat, head and neck and to develop new treatments and cures. In the 2019–2020 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #4 in the nation for eye care and #2 for ear, nose and throat care. For more information about life-changing care and research at Mass. Eye and Ear, visit our blog, Focus, and follow us on Instagram, Twitter and Facebook. About Massachusetts General Hospital Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2019 the MGH was once again named #2 in the nation by U.S. News & World Report in its list of "America’s Best Hospitals." About Harvard Medical School Department of Ophthalmology The Harvard Medical School Department of Ophthalmology is one of the leading and largest academic departments of ophthalmology in the nation. Composed of nine affiliates (Massachusetts Eye and Ear, which is home to Schepens Eye Research Institute; Massachusetts General Hospital; Brigham and Women’s Hospital; Boston Children’s Hospital; Beth Israel Deaconess Medical Center; Joslin Diabetes Center/Beetham Eye Institute; Veterans Affairs Boston Healthcare System; Veterans Affairs Maine Healthcare System; and Cambridge Health Alliance) and several international partners, the department draws upon the resources of a global team to pursue a singular goal—eradicate blinding diseases so that all children born today will see throughout their lifetimes. Formally established in 1871, the department is committed to its three-fold mission of providing premier clinical care, conducting transformational research, and providing world-class training for tomorrow’s leaders in ophthalmology. About Penn Medicine Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.6 billion enterprise. The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year. The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Home Care and Hospice Services, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
ATS Researchers fail to find subphenotypes of COVID-19 ARDS. Newswise — May 27, 2020─ In a new paper published online in the Annals of the American Thoracic Society, researchers have been unable to produce two theorized subphenotypes of COVID-19 related acute respiratory distress syndrome (ARDS). Scientists previously proposed that two phenotypes exist that differentiate patients with more severe COVID-19 and indicate that they should be treated differently. A phenotype is a set of characteristics used to classify a patient, which may influence disease management. In “Subphenotyping ARDS in COVID-19 Patients: Consequences for Ventilator Management,” Lieuwe D.J. Bos, MD, PhD, and co-authors report on a retrospective analysis of the first 38 patients with suspected COVID-19 who were admitted to the ICU of the Academic Medical Center of the University of Amsterdam, The Netherlands. CT scans were done shortly after these patients were intubated and before they were admitted to the ICU. The scans were analyzed and compared with each other to determine factors that might indicate different phenotypes of COVID-19 ARDS. “Our finding was that most patients do not fulfill the criteria of one phenotype or the other,” said Dr. Bos, clinician and researcher in respiratory medicine and intensive care, Amsterdam University Medical Center. “I do not feel encouraged to spilt patients into the two proposed phenotypes to guide ventilator management, but rather treat patients with the uniform, high quality care that we always deliver to patients with lung injury.” Some scientists have hypothesized that patients can either develop typical ARDS, which has recently been called “H type,” or that they develop “L type” ARDS. In H type, a patient’s lung collapses easily (high elastance) resulting in higher lung weight due to pulmonary edema, a condition in which the lungs fill with fluid. Blood flows through areas that are not ventilated (higher shunt) and collapsed lungs can be opened by using positive pressure ventilation. The “L” phenotype would have low elastance, which means lung tissue does not collapse easily, and because of this, the weight of the lung is low (normal) and most of the blood flows through areas where there is ventilation (low shunt). The problem in these patients might be that blood vessels in the lungs dysfunction. Several steps have to be taken before subphenotype-targeted treatment can be put into clinical practice, the last step being a head-to-head comparison of subphenotype-directed treatment with standard of care in a randomized clinical trial. Before this step is taken, however, the basic assumptions underlying the subclassifications of patients must be validated. Dr. Bos and colleagues sought to invalidate this theory and hypothesized that patients with low elastance also show little consolidation on chest CT scan images – and vice versa. The researchers performed CT scans right after intubation and before transport to the ICU. They estimated lung consolidation area for patients classified as having either an H- or L-phenotype, classified lung morphology as focal (back side of lung) or non-focal, and conducted a number of other calculations. They found that in patients with a non-focal lung morphology, lung weight and lower respiratory compliance were not related at all. The authors stated: “Based on these preliminary data, we conclude that compliance and an estimation of lung weight do not correlate in patients with COVID-19 related ARDS. Most patients could not be classified as either ‘H’ or ‘L’ subphenotype, but showed mixed features. “The presented data are the first independent test of proposed subphenotypes of COVID-19 related ARDS and highlight that features of the H- and L-subphenotypes are not mutually exclusive. Simultaneously, we validated the existence of heterogeneity in lung morphology known from non-COVID-19 related ARDS. We need data-driven approaches to evaluate the existence of treatable traits to improve patient-centered care. Until these data become available, an evidence-based approach extrapolating data from ARDS not related to COVID-19 is the most reasonable approach for ICU care.”