Scientists at Scripps Research, University of Chicago and Icahn School of Medicine at Mount Sinai have identified a new Achilles' heel of influenza virus, making progress in the quest for a universal flu vaccine. Antibodies against a long-ignored section of the virus, which the team dubbed the anchor, have the potential to recognize a broad variety of flu strains, even as the virus mutates from year to year, they reported Dec. 23, 2021 in the journal Nature.
"It's always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design," says co-senior author Andrew Ward, Ph.D., professor of Integrative Structural and Computational Biology at Scripps Research. "It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover."
"By identifying sites of vulnerability to antibodies that are shared by large numbers of variant influenza strains we can design vaccines that are less affected by viral mutations," says study co-senior author Patrick Wilson, MD, who was previously at the University of Chicago and recently recruited to Weill Cornell Medicine as a professor of pediatrics and a scientist in the institution's Gale and Ira Drukier Institute for Children's Health. "The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications."
Generalized pustular psoriasis (GPP) is a rare, life-threatening skin condition for which there are no approved treatments. It is characterized by episodes of widespread eruptions of painful, sterile pustules (blisters of non-infectious pus). There is a high unmet need for treatments that can rapidly and completely resolve the signs and symptoms of GPP flares. Flares greatly affect a person's quality of life and can lead to hospitalization with serious complications, including heart failure, renal failure, sepsis, and death.
A clinical trial has shown that spesolimab is a novel, humanized, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogeneses of several autoimmune diseases, including generalized pustular psoriasis. The novel drug demonstrated rapid clearance of pustules in adult patients with generalized pustular psoriasis (GPP) experiencing a flare.
The study met the primary endpoint; 54% of patients had no visible pustules after a single dose of spesolimab, compared to 6% receiving a placebo at week one.
The bottom line appears to be that spesolimab is rapidly effective in the majority of patients within one week of its first intravenous infusion for patients suffering from generalized pustular psoriasis. This is significant because generalized pustular psoriasis is a life-threatening condition that compromises the integrity of the skin. Patients are frequently hospitalized and often die from sepsis or other complications.
Newly developed injectable, adhesive surgical gel to prevent scar tissue https://medicalxpress.com/news/2021-12- ... -scar.html
by Guangdong Engineering Research Center for Translation of Medical 3D Printing Application
Up to 90% of patients who undergo open abdominal or pelvic surgery develop postoperative adhesions, or scar tissue. Minimally invasive laparoscopic surgical approaches can reduce the severity of the adhesions, but the scar tissue still forms. The cellular response to injury—even intentional injury, such as surgery to repair a problem—results in a cascade of molecules pouring to the site to heal the tissue. But the molecules, working quickly to close the wound, often go too far and bind the wound to nearby healthy tissue. Depending on the location, the resulting scar tissue can cause chronic pain, bowel obstruction and even death.
There may be a potential solution available soon, according to researchers from Southern Medical University in China. They have developed an injectable hydrogel that can plug up wounds without sticking to off target tissue, effectively preventing postoperative adhesions.
Their approach, tested in rats and rabbits, was published on Nov. 18 in Advanced Functional Materials.
According to paper author Yaobin Wu, associate professor, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Southern Medical University in China, many antiadhesive barriers are hydrogels inspired by mussels, marine animals that can adhere to strongly to other materials. Hydrogels can bond to wet tissue and are typically designed as double-sided adhesive materials, which increases the risk of postoperative adhesions. A class of hydrogels are asymmetric, with only one adhesive side, which reduces the risk of adhesions, but their preparation method makes them uninjectable and unsuitable for laparoscopic surgery, Wu said.
A once-a-day antiretroviral medicine that is low-cost and easy for children to take is also more effective at suppressing HIV than standard treatments, according to a global trial led by researchers at UCL.
The study, published today in The New England Journal of Medicine, found that dolutegravir-based regimens, which are already widely used to treat adults, reduced the chances of treatment failure among young people aged 3 to 18 by around 40% compared to standard treatments.
The findings were based on a randomized controlled trial called ODYSSEY involving more than 700 children from 29 clinical centers in Africa, Europe and Asia, who were randomly given either dolutegravir or standard anti-HIV drugs, and who were followed up for at least two years.
Minutes matter when the brain is being deprived of oxygen.
Doctors at MUSC Health's Comprehensive Stroke Center constantly work with their community hospital colleagues on initiatives to cut down the steps that need to happen between the time a stroke patient is wheeled through the ambulance bay until treatment can begin—for example, by developing a TeleEMS program so emergency medical technicians can consult with stroke specialists while inside a patient's home or the back of the ambulance.
Some things still need to happen at the hospital before treatment can begin, though, like scans of the brain to confirm a stroke and determine what type it is.
But a neuroradiologist with her eyes on the stars wondered if a new portable MRI that she hopes to use in space might also be of use to patients in rural areas of South Carolina.
"I realized that if you have a scanner that can be used in extreme environments such as space, it can also be very useful for patients here on Earth," said Donna Roberts, M.D., who studies how zero gravity and microgravity affect astronauts' brains.
To that end, she got together with Christine Holmstedt, D.O., medical director of the Comprehensive Stroke Center; Sami Al Kasab, M.D., associate medical director of the MUSC Health Teleneuroscience Program; and Michael Haschker, manager of telehealth technologies in the MUSC Health Center for Telehealth, to test the idea.
Monitoring a person's blood pressure on a regular basis can help health care professionals with early detection of various health problems such as high blood pressure, which has no warning signs or symptoms. However, many things can alter an accurate blood pressure reading, including a patient's nervousness about having their blood pressure taken at a doctor's office, otherwise known as "white coat syndrome."
Now, researchers at the University of Missouri are customizing a commercial finger clip device to provide a rapid, noninvasive way for measuring and continually monitoring blood pressure. The device can also simultaneously measure four additional vital signs—heart rate, blood oxygen saturation, body temperature and respiratory rate, said Richard Byfield, a mechanical and aerospace engineering graduate student in the MU College of Engineering, and the lead author on the study.
Implementing a multi-stage screening process for autism spectrum disorder in early intervention settings may lead to a significant increase in ASD detection compared to standard care, particularly among Spanish-speaking children.
Autism spectrum disorder (ASD) typically develops in children before age 3, but less than half of children are accurately diagnosed with ASD before age 4. Although pediatric advocates recommend that children at risk of ASD receive screening through early intervention (EI) services provided by states, the program often lacks effective screening tools to detect and diagnose this disorder.
Now, a new study led by a Boston University School of Public Health (BUSPH) researcher found that implementing a multi-stage screening protocol for ASD in early intervention services may lead to a 60 percent increase in ASD detection, compared to standard screening.
Published in the journal JAMA Pediatrics, the study also underscored the importance of monitoring for disparities in ASD. The increased rate of ASD detection was nearly twice as high for Spanish-speaking families as for non-Spanish-speaking families, helping to reduce a well-documented health disparity.
The study is the first comprehensive evaluation of ASD screening in EI settings and includes comparison with non-screened EI settings. Unlike standard approaches to screening, which are often limited to providing questionnaires for parents, the multi-component screening protocol in this study includes input from parents and EI providers in the decision-making process for a child's ASD diagnosis, as well as training for EI providers and ongoing collaboration between the EI providers and the EI sites' program directors and research assistants.
Enzymes are biology's catalytic workhorses, binding molecules together, splitting them apart and reconfiguring them in processes vital to everything from digestion to breathing. Their availability, efficiency and specificity have long made them popular for reactions outside biological systems as well, including those involved in food preservation, detergents and disease diagnostics.
"Enzymes are nature's privileged catalysts," said UC Santa Barbara assistant professor of chemistry Yang Yang. "They can catalyze reactions with amazing selectivity." Efforts over the past three decades have also resulted in the development of customized enzymes—enzymes rapidly evolved for directed purposes, to interact with specific molecules, resulting in a high yield of desired products with unparalleled selectivities.
However, Yang added, the reactions that enzymes can allow for are relatively limited—a somewhat small repertoire for their powerful ability to efficiently make products at lower material, energy and environmental costs.
To bridge that gap and merge the best of both worlds—versatility and selectivity—Yang and his research team have developed a method by which certain enzymes can be coaxed into facilitating useful reactions that were never previously observed in the biological world, thereby widening their repertoire and opening possibilities for processes never before conducted by enzymes.
A recent study links anxiety behavior in rats, as well as post traumatic stress disorder (PTSD) in military veterans, to increased myelin—a substance that expedites communication between neurons—in areas of the brain associated with emotions and memory.
The results, reported by scientists at the University of California, Berkeley, and UC San Francisco (UCSF), provide a possible explanation for why some people are resilient and others vulnerable to traumatic stress, and for the varied symptoms—avoidance behavior, anxiety and fear, for example—triggered by the memory of such stress.
Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have discovered a new gene that plays an important role in the way the spleen functions, potentially leading to new treatments for infectious diseases.
The study, published in Science Immunology, also uncovered multiple new spleen cells and revealed the distinct way they respond in order to fight off different infections.
The spleen plays a key role in the immune responses that protect the body against various diseases and infections such as virus infections, malaria and sepsis, and also plays a key role in the immune response to vaccines. However, it has not been known how the spleen functions to support this response.
University of Melbourne Professor Scott Mueller, a Laboratory Head at the Doherty Institute and lead author on the paper, explained that while it is known the spleen is made up of various networks of cells called fibroblasts, a clear picture of how these cells are constructed and function, was lacking.
"Using novel biological tools and next generation sequencing, we were able to examine precisely how specialized types of fibroblast cells dictate how the spleen works to protect against infections," Professor Mueller explained.
"We performed next-generation sequencing to understand what genes are expressed by fibroblasts in the spleen. We used advanced fluorescent microscopy to visualize the 3D networks of cells in the spleen.
WEHI researchers have produced the first molecular images of an enzyme that controls proteins to signal and communicate with each other in human cells. The discovery could help to solve the mystery cause of a rare group of hereditary neurodegenerative diseases linked to deregulation of this enzyme.
In the study, published in Molecular Cell, Dr. Thomas Cotton, Dr. Bernhard Lechtenberg and colleagues at WEHI solved the first three-dimensional (3D) structure of an enzyme called RNF216. The team captured molecular 'snapshots' of RNF216 as it assembled chains of the small protein ubiquitin, which tags the target proteins to modify their behavior in the cell. They also showed how RNF216 dictates the type of ubiquitin chain that is formed—the first time that this has been explained.
Mutations in RNF216 have been linked to Gordon-Holmes Syndrome, a very rare neurodegenerative disorder that results in reproductive problems, movement disorders, and progressive cognitive decline and dementia.
In 1st, US surgeons transplant pig heart into human patient
Source: AP
By CARLA K. JOHNSON
In a medical first, doctors transplanted a pig heart into a patient in a last-ditch effort to save his life and a Maryland hospital said Monday that he’s doing well three days after the highly experimental surgery.
While it’s too soon to know if the operation really will work, it marks a step in the decades-long quest to one day use animal organs for life-saving transplants. Doctors at the University of Maryland Medical Center say the transplant showed that a heart from a genetically modified animal can function in the human body without immediate rejection.
The patient, David Bennett, a 57-year-old Maryland handyman, knew there was no guarantee the experiment would work but he was dying, ineligible for a human heart transplant and had no other option, his son told The Associated Press.
“It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” Bennett said a day before the surgery, according to a statement provided by the University of Maryland School of Medicine.
In this photo provided by the University of Maryland School of Medicine, members of the surgical team show the pig heart for transplant into patient David Bennett in Baltimore on Friday, Jan. 7, 2022. On Monday, Jan. 10, 2022 the hospital said that he's doing well three days after the highly experimental surgery. (Mark Teske/University of Maryland School of Medicine via AP)
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Researchers at Penn Medicine have discovered a new, more effective method of preventing the body's own proteins from treating nanomedicines like foreign invaders, by covering the nanoparticles with a coating to suppress the immune response that dampens the therapy's effectiveness.
When injected into the bloodstream, unmodified nanoparticles are swarmed by elements of the immune system called complement proteins, triggering an inflammatory response and preventing the nanoparticles from reaching their therapeutic targets in the body. Researchers have devised some methods to reduce this problem, but the Penn Medicine team, whose findings are published in Advanced Materials, has invented what may be the best method yet: coating nanoparticles with natural suppressors of complement activation.
Nanoparticles are tiny capsules, typically engineered from proteins or fat-related molecules, that serve as delivery vehicles for certain types of treatment or vaccine—usually those containing RNA or DNA. The best-known examples of nanoparticle-delivered medicines are mRNA vaccines against COVID-19.
"It turned out to be one of those technologies that just works right away and better than anticipated," said study co-senior author Jacob Brenner, MD, Ph.D., an associate professor of Pulmonary Medicine in the Division of Pulmonary, Allergy, and Critical Care.
Whether you are taking a muscle relaxant or a heart medication, you are possibly using a medication that contains a synthetically produced benzoxazole. Although natural benzoxazoles show more significant promise in pharmaceuticals, their time to develop organically and inherent undesired properties impede their usage.
Dr. Xuejun Zhu, assistant professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, alongside graduate student Huanrong Ouyang, and two undergraduate students, Joshua Hong and Jeshua Malroy are synthesizing natural benzoxazoles using E. coli in hopes of developing a more efficient, eco-friendly and cost-effective method of producing them for future drug development.
Their research was published in the American Chemical Society's journal ACS Synthetic Biology 2021.
Benzoxazole is a heterocyclic compound composed of carbon, hydrogen, oxygen and nitrogen. It can be produced synthetically but is also found in bioactive natural products like nataxazole, caboxamycin and calcimycin. Synthetically created benzoxazoles are found in synthetic pharmaceuticals ranging from chlorzoxazone (a muscle relaxant) to tafamidis (for treating heart disease).
(EurekAlert) The urea cycle is responsible for removing nitrogenous waste produced from the breakdown of protein in the organism. If the OTC enzyme is missing in this cycle, ammonia accumulation rises to toxic levels. An OTC deficiency is the most common disorder in the urea cycle. It could not be cured with drugs until now.
The OTC gene is located on the sex chromosome (X chromosome). This means that the manifestation of the disorder is usually weaker in female newborns. However, in male newborns, who have one X and one Y chromosome, a deficiency in the OTC gene has a dramatic effect: In newborn boys, ammonia toxicity due to OTC deficiency is often fatal. The research team looked for ways to test drugs in the lab against the OTC deficiency.
Created an initial model
First the research team generated liver cells from patients’ skin tissue in an elaborate process. It worked like this: Initially, a tissue sample of the skin was taken from OTC-deficient patients as well as from a control group (healthy individuals). In a complex process, the samples were differentiated so that they functioned like stem cells. This engineering process was developed by Shin’Ya Yamanaka, for which he was awarded the Nobel Prize in Medicine in 2012. “By using induced stem cell technology, we succeeded in generating liver cells that function largely like liver cells from patients,” explains Dr. med. Alexander Lämmle, Senior Physician at the Department of Pediatrics and the University Institute of Clinical Chemistry at Inselspital. “However, we observed that the induced liver cells excrete significantly less urea than real, healthy liver cells, and this is independent of whether they originate from healthy controls or urea cycle patients.” The researchers were able to determine the reason for this behavior. The technologically engineered stem cells were characterized by a complete lack of aquaporin 9, a transport protein in the cell membrane. The reason for this deficiency is the still immature, fetal character of the artificial liver cells.
Aquaporin 9: the key to a functioning artificial liver cell,
Aquaporins organize the transport of water and certain substances through the cell membrane. Aquaporin 9 is responsible for the transport of urea...
A new study by researchers at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, has identified a new potential pathway for developing therapeutics that target Epstein-Barr virus (EBV). They discovered that the way the EBV genome folds, and thereby expresses itself and causes disease, is more complex than researchers originally thought, and they identified molecules that could be targeted to disrupt this folding.
"We identified two cellular proteins that are important to folding the EBV genome." said Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program at The Wistar Institute and corresponding author on the paper. "There are existing drugs that target one of these proteins. And our data suggests that if we use that drug on EBV infected cells, we have a way in which we can actually interfere with the folding. That means we can interfere in the way in which the EBV viral genome is functioning."
(Science Alert) After 700 days of antibiotic treatment, the infection of a 30-year-old bombing attack victim still raged.
Tragically, the patient had suffered life-threatening injuries during the attacks at Brussels airport on 22 March 2016. Over the next three years, she faced numerous medical complications, as her fracture-related wound became infected with pan-drug-resistant bacteria, or what we know colloquially as superbugs.
Confronted with little progress, clinicians decided to turn to a combination of antibiotics and specialized bacteriophage therapy, a new treatment that harnesses specialized viruses that infect and kill bacteria. Her unique and successful case has now been described in Nature Communications.
Superbug infections are becoming an increasingly serious health issue, with phage therapy being amongst the most promising new tools in our arsenal.
Normally, phages infect a subset of strains of bacteria that belong to a single bacterial species, however, clinicians have been working on personalized forms of phage therapy, where phages from a prepared bank are selected by analyzing the bacterial strains isolated from the patient's bacterial infection.
A research team led by a biomedical scientist at the University of California, Riverside, has discovered a new immune pathway in chickens that viruses—such as those that tend to infect birds, humans, and animals and spread diseases like influenza or Crimean-Congo hemorrhagic fever—may be targeting.
The discovery, which has implications also for diseases affecting other birds, sheds greater light on birds' immune responses to zoonotic viruses—specifically, how those may differ from responses seen in humans.
"Understanding these differences is critical to better understanding birds as potential reservoirs of human pathogens," said Scott Pegan, a professor of biomedical sciences in the UC Riverside School of Medicine, who led the study published in Frontiers in Immunology. "Additionally, it allows researchers to better understand the immune pathways that might lead to effective vaccines for agriculture use in poultry."
A robot has performed laparoscopic surgery on the soft tissue of a pig without the guiding hand of a human—a significant step in robotics toward fully automated surgery on humans. Designed by a team of Johns Hopkins University researchers, the Smart Tissue Autonomous Robot (STAR) is described today in Science Robotics.
"Our findings show that we can automate one of the most intricate and delicate tasks in surgery: the reconnection of two ends of an intestine. The STAR performed the procedure in four animals and it produced significantly better results than humans performing the same procedure," said senior author Axel Krieger, an assistant professor of mechanical engineering at Johns Hopkins' Whiting School of Engineering.
The robot excelled at intestinal anastomosis, a procedure that requires a high level of repetitive motion and precision. Connecting two ends of an intestine is arguably the most challenging step in gastrointestinal surgery, requiring a surgeon to suture with high accuracy and consistency. Even the slightest hand tremor or misplaced stitch can result in a leak that could have catastrophic complications for the patient.
