miércoles, 30 de septiembre de 2020

Coronavirus Deaths Pass One Million Worldwide - The New York Times

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“It seems to people who are on lockdown that it’s going on interminably, but for scientists it’s just the beginning.”

As we reach the terrible milestone of one million deaths attributed to COVID-19, evolutionary biologist Martha Nelson notes that many unanswered questions about the coronavirus remain. (The New York Times | 6 min read)

Coronavirus Deaths Pass One Million Worldwide - The New York Times

One million deaths — at least

More than one million people have died from COVID-19. Probably many more, because the true tally of those lost to the disease is achingly difficult to determine. Countries have had varying levels of success at protecting their citizens from a pandemic that scientists had long predicted. “This is a very serious global event, and a lot of people were going to get sick and many of them were going to die, but it did not need to be nearly this bad,” said Tom Inglesby, the director of the Johns Hopkins Center for Health Security.

The New York Times | 6 min read
Read more: Researchers are struggling to gauge the true toll of the coronavirus outbreak (Nature | 11 min read, from September)

Britain's failure to learn the hard lessons of its first Covid surge is a disaster | William Hanage | Opinion | The Guardian

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“Britain is in the grip of an extraordinarily dangerous outbreak of forgetfulness.”

Epidemiologist William Hanage says the United Kingdom, where COVID-19 cases are rising rapidly, has not learnt the hard lessons from its first surge early in the year. (The Guardian | 7 min read)

COVID-19 data on Native Americans is ‘a national disgrace.’ This scientist is fighting to be counted | Science | AAAS

The unequal toll on Native Americans

American Indians and Alaska Natives are 3.5 times more likely to be diagnosed with COVID-19 than are non-Hispanic white people, according to an analysis of data from 23 US states by Abigail Echo-Hawk. But gaps in reporting mean that the full impact of the pandemic on Indigenous communities remains unclear. “The data is a national disgrace,” says Echo-Hawk, a citizen of the Pawnee Nation of Oklahoma and director of the Urban Indian Health Institute. “How can decisions be made in the United States to prevent, intervene, and treat COVID-19, when you can’t even truly tell what populations are most affected?”
Science | 8 min read
Reference: Morbidity and Mortality Weekly Report

SARS-CoV-2 vaccines in development | Nature

The SARS-CoV-2 vaccine landscape now

Virologist and vaccinologist Florian Krammer offers a comprehensive review of the SARS-CoV-2 vaccine landscape, including the status of the front-running candidates and their approaches. He also notes the enormous practical challenges and many unanswered questions, such as how long vaccine immunity will persist. The outlook is “cautiously positive”, writes Krammer. “It is certainly possible that vaccines with safety and efficacy proven in phase III trials might already enter the market in 2020.” Krammer’s epic 138-tweet thread spells it out in simpler terms.

Nature | 37 min read or Twitter thread

Read: Adult Mental Health Treatment: United States, 2019

NCHS Data Brief, Number 380, September 2020

Mental Health Treatment Among Adults: United States, 2019

Key findings
Data from the National Health Interview Survey

In 2019, 19.2% of adults had received any mental health treatment in the past 12 months, including 15.8% who had taken prescription medication for their mental health and 9.5% who received counseling or therapy from a mental health professional.
Women were more likely than men to have received any mental health treatment.
Non-Hispanic white adults (23.0%) were more likely than non-Hispanic black (13.6%) and Hispanic (12.9%) adults to have received any mental health treatment.
Overall, as the level of urbanization decreased, the percentage of adults who had taken medication for their mental health increased, and the percentage who had received counseling or therapy decreased.

Keywords

medication, counseling and therapy, National Health Interview Survey (NHIS)

Full Report in HTML >

Full Report in PDF >

Immunization Works Newsletters | CDC

Computer-designed proteins may protect against coronavirus | National Institutes of Health (NIH)

Computer-designed proteins may protect against coronavirus

At a Glance

Researchers designed “miniproteins” that bound tightly to the SARS-CoV-2 spike protein and prevented the virus from infecting human cells in the lab.
More research is underway to test the most promising of the antiviral proteins.

An artist’s conception of computer-designed miniproteins (white) binding coronavirus spikes. UW Institute for Protein Design

The surface of SARS-CoV-2, the virus that causes COVID-19, is covered with spike proteins. These proteins latch onto human cells, allowing the virus to enter and infect them. The spike binds to ACE2 receptors on the cell surface. It then undergoes a structural change that allows it to fuse with the cell. Once inside, the virus can copy itself and produce more viruses.

Blocking entry of SARS-CoV-2 into human cells can prevent infection. Researchers are testing monoclonal antibody therapies that bind to the spike protein and neutralize the virus. But these antibodies, which are derived from immune system molecules, are large and not ideal for delivery through the nose. They’re also often not stable for long periods and usually require refrigeration.

Researchers led by Dr. David Baker of the University of Washington set out to design synthetic “miniproteins” that bind tightly to the coronavirus spike protein. Their study was funded in part by NIH’s National Institute of General Medical Sciences (NIGMS) and National Institute of Allergy and Infectious Diseases (NIAID). Findings appeared in Science on September 9, 2020.

The team used two strategies to create the antiviral miniproteins. First, they incorporated a segment of the ACE2 receptor into the small proteins. The researchers used a protein design tool they developed called Rosetta blueprint builder. This technology allowed them to custom build proteins and predict how they would bind to the receptor.

The second approach was to design miniproteins from scratch, which allowed for a greater range of possibilities. Using a large library of miniproteins, they identified designs that could potentially bind within a key part of the coronavirus spike called the receptor binding domain (RBD). In total, the team produced more than 100,000 miniproteins.

Next, the researchers tested how well the miniproteins bound to the RBD. The most promising candidates then underwent further testing and tweaking to improve binding.

Using cryo-electron microscopy, the team was able to build detailed pictures of how two of the miniproteins bound to the spike protein. The binding closely matched the predictions of the computational models.

Finally, the researchers tested whether three of the miniproteins could neutralize SARS-CoV-2. All protected lab-grown human cells from infection. Candidates LCB1 and LCB3 showed potent neutralizing ability. These were among the designs created from the miniprotein library. Tests suggested that these miniproteins may be more potent than the most effective antibody treatments reported to date.

“Although extensive clinical testing is still needed, we believe the best of these computer-generated antivirals are quite promising,” says Dr. Longxing Cao, the study’s first author. “They appear to block SARS-CoV-2 infection at least as well as monoclonal antibodies but are much easier to produce and far more stable, potentially eliminating the need for refrigeration.”

Notably, this study demonstrates the potential of computational models to quickly respond to future viral threats. With further development, researchers may be able to generate neutralizing designs within weeks of obtaining the genome of a new virus.

—by Erin Bryant

Poor immune response impairs diabetic wound healing

At a Glance

Researchers found that diabetic foot ulcers don’t recruit the immune cells necessary for normal wound healing.
The team also identified factors that contribute to this impaired immune response, pointing to potential targets for future therapies.

Symptoms of diabetes include sores that don’t heal properly. These can lead to diabetic foot ulcers.MangTeng / iStock / Getty Images Plus

Diabetes occurs when your blood glucose, also called blood sugar, is too high. Over time, having too much sugar in your blood can cause health problems, such as heart disease, nerve damage, eye problems, and kidney disease.

Diabetes can also reduce the ability of the skin to heal itself. Even small cuts on the feet can develop into diabetic foot ulcers—chronic, non-healing wounds that are vulnerable to infection. Diabetic foot ulcers are a major cause of lower limb amputations, disability, and death in people with diabetes.

Treatment options for people with diabetic foot ulcers are limited. A better understanding about how the healing process goes awry in these wounds could help researchers design better therapies and diagnostic tools.

A team led by Dr. Maria Morasso from NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Dr. Marjana Tomic-Canic from the University of Miami looked closely at the inflammatory response in diabetic foot ulcers. Inflammation is caused by the immune system’s reaction to injury or infection. It is a necessary part of the healing process, but if not properly controlled can prevent wounds from healing.

The researchers took tissue samples from the edge of diabetic foot ulcers in 13 people. They used multiple methods to compare these with samples from normally healing small wounds in the mouth and skin of people without diabetes. The mouth wounds provided samples of tissue known to heal very quickly with little or no scarring. The study results were published on September 16, 2020, in Nature Communications.

Neutrophils (teal) gather at the site of a human skin wound at day three to promote an inflammatory response during healing. Dr. Andrew Sawaya, NIAMS Laboratory of Skin Biology

Analysis of wounds a few days after injury showed that some gene activity patterns were similar among healthy oral and skin wounds and diabetic foot wounds. However, many processes associated with inflammation and healing were suppressed in the diabetic foot ulcers.

The team found that several genes that help promote tissue repair were highly active in healthy mouth and skin wounds but suppressed in diabetic foot wounds. Two of these genes, FOXM1 and STAT3, are involved in recruiting immune cells necessary for healthy inflammation and wound healing.

Immune cell activity in diabetic foot ulcers differed from that in healthy mouth and skin wounds. Recruitment of neutrophils and macrophages to the injury site, which is necessary for wound healing, was suppressed in the diabetic foot ulcers. Other immune cells that reflect a stalled healing process were more likely to be found in the foot ulcers.

The team next directly tested the role of the FOXM1 protein in wound healing in diabetic mouse models. They applied a compound that blocks FOXM1 to skin wounds. Mice given the compound showed substantially delayed wound healing, similar to people with diabetic foot ulcers. The compound also significantly decreased the number of neutrophils and macrophages in the diabetic wounds.

“Though diabetic foot ulcers are a complex disease with likely many contributing factors, loss of FOXM1 appears to play a role in delayed healing,” Morasso says. “Modulating its function in chronic, non-healing wounds may be a potential therapeutic strategy to restart the stalled healing process.”

—by Sharon Reynolds

How anesthetics and benzodiazepine affect the brain differently

At a Glance

Researchers identified how anesthetic and benzodiazepine drugs change a brain receptor’s shape, providing a new level of detail in understanding anesthesia.
The results suggest ways to design more tailored anesthetic drugs in the future.

A GABA receptor embedded in a cell membrane bound with propofol. The receptor subunits are in green, blue, and yellow. Propofol, colored in salmon, is between subunits. The phospholipids that make up the cell membrane are in gray with their head groups red and orange. University of Texas Southwestern Medical Center

General anesthetics are used to put patients to sleep before surgical procedures. Many general anesthetics work primarily through a brain protein called the GABAA receptor. Benzodiazepines, another widely prescribed type of sedative, also act through this same receptor. However, benzodiazepines have a wide range of calming effects. Low doses can make you feel sedated and high doses can act as an anesthetic. They’re often used to treat anxiety, epilepsy, and insomnia.

The GABAA receptor forms a channel through cell membranes. The molecule in the brain that activates the receptor is called GABA. It causes the channel to open, letting in ions to quiet the brain cells’ activity. But how anesthetics and benzodiazepines can have different sedating effects hasn’t been clearly understood.

To better understand how these drugs interact with the GABAA receptor, a research team led by Drs. Jeong Joo Kim and Ryan Hibbs from the University of Texas Southwestern Medical Center mapped the receptor’s atomic structure while it interacted with three different anesthetic drugs (phenobarbital, etomidate, and propofol) and a commonly used benzodiazepine drug called diazepam. The team also mapped the receptor’s interactions with a drug used to treat benzodiazepine overdoses, called flumazenil.

The work was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Drug Abuse (NIDA). Results were published on September 2, 2020 in Nature.

Using a technique called cryogenic electron microscopy, or cryo-EM, the team froze and imaged the GABAA receptor while interacting with each individual drug. They mapped where each one bound to the receptor. They found that the anesthetic drugs and the benzodiazepine bound to the receptor at both distinct and overlapping sites.

The researchers also compared changes in the receptor’s shape when it interacted with each drug. When the anesthetic drugs bound the receptor, they stabilized the channel in a more open shape. This change makes it easier for GABA to open the channel and calm the activity of the brain cell.

Diazepam also shifted the receptor’s structure so the channel could be more easily opened, but to a lesser degree. Flumazenil destabilized the site where diazepam, etomidate, and propofol bind, suggesting how it may reverse the action of benzodiazepines and some general anesthetics.

“The fact that there are differences in the binding sites gives us some hope that we might be able to create more specific molecules that bind to only one site on the GABAA receptor,” Hibbs says. “This is now a launching point for the discovery of improved, more selective anesthetics.”

—by Tianna Hicklin, Ph.D.

Experts Next Door: How a Public-Private Partnership Benefits the Regenerative Medicine Community

Blue cells with orange centers float on a blue background.

By Catherine (Katie) Zander, a scientific program manager at the Standards Coordinating Body

I’m a scientific program manager at the Standards Coordinating Body (SCB), a private nonprofit organization devoted to advancing standards for regenerative medicine, an emerging field that includes cell therapies, immunotherapies, tissue engineering and other next-generation treatments. Presently, or rather, until the coronavirus intervened, we share office space on the National Institute of Standards and Technology (NIST) campus in Gaithersburg, Maryland.

A few months ago, I was searching for experts who worked with organ-on-a-chip systems, which use cells flowing through tiny channels to simulate organs and organ systems, for the SCB-coordinated Microphysiological Systems project, which, among other things, is seeking to create a common vocabulary for describing these devices’ capabilities. I was chatting with the NIST researcher next door. When she asked what I was working on, I told her. She laughed and said, “Well, that’s what I do!” We walked down to her laboratory, and she showed me her work.

EL BIRUNI: CIENCIAS MÉDICAS NEWS [https://elbiruniblogspotcom.blogspot.com.ar] ▲ DIRECTORIO DE DOCUMENTOS EDITADOS EN SEPTIEMBRE de 2020 [*] ► Contenidos Copyright by Cerasale Morteo, Víctor Norberto; 2008 a 2020. SALTA / ARGENTINA. 30 de SEPTIEMBRE de 2020 [16/0159] - DOCE AÑOS AGREGANDO VALOR A LA INVESTIGACIÓN MÉDICA, A LAS CIENCIAS MÉDICAS APLICADAS Y AL CONOCIMIENTO DE LOS PACIENTES Y SUS FAMILIARES

EL BIRUNI: CIENCIAS MÉDICAS NEWS [https://elbiruniblogspotcom.blogspot.com.ar] ▲ DIRECTORIO DE DOCUMENTOS EDITADOS EN SEPTIEMBRE de 2020 [*] ► Contenidos Copyright by Cerasale Morteo, Víctor Norberto; 2008 a 2020. SALTA / ARGENTINA. 30 de SEPTIEMBRE de 2020 [16/0159] - DOCE AÑOS AGREGANDO VALOR A LA INVESTIGACIÓN MÉDICA, A LAS CIENCIAS MÉDICAS APLICADAS Y AL CONOCIMIENTO DE LOS PACIENTES Y SUS FAMILIARES

SABIDURÍA IMPLICA HUMILDAD

EL BIRUNI: MEDICAL SCIENCES NEWS [https://elbiruniblogspotcom.blogspot.com.ar] ▲ DIRECTORY OF DOCUMENTS PUBLISHED IN SEPTEMBER 2020 [*] ► Contents Copyright by Cerasale Morteo, Víctor Norberto; 2008 to 2020. SALTA / ARGENTINA. SEPTEMBER 30, 2020 [16/0159]
TWELVE YEARS ADDING VALUE TO MEDICAL RESEARCH, TO APPLIED MEDICALSCIENCES AND TO THE KNOWLEDGE OF PATIENTS AND THEIR FAMILY MEMBERS

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