#masthead-section-label, #masthead-bar-one { display: none }El brote de coronavirusVacunas: lo que debes saberIdentifica las N95 falsasEficacia vs. EfectividadAsí funciona la Sputnik V¿Una vacuna cubana?AdvertisementContinue reading the main storySupported byContinue reading the main storyLas mujeres informan de peores efectos secundarios tras la vacuna para la covidLos hombres y las mujeres suelen responder de forma diferente a muchos tipos de vacunas. Esto se debe probablemente a una mezcla de factores, como las hormonas, los genes y la dosis de las vacunas.Los investigadores de los CDC analizaron los datos de seguridad de 13,7 millones de vacunas para la COVID-19 y descubrieron que el 79,1 por ciento de los efectos secundarios notificados procedían de mujeres, aunque solo el 61,2 por ciento de las vacunas se habían administrado a mujeres.Credit…Mike Kai Chen para The New York Times10 de marzo de 2021 a las 15:51 ETRead in EnglishLa mañana que Shelly Kendeffy recibió su segunda dosis de la vacuna de Moderna contra la COVID-19, se sintió bien. En la tarde, sintió el brazo adolorido y dolor corporal, y para la noche, tenía síntomas parecidos a los de la influenza.“Los dientes me castañeteaban, pero estaba sudando… como empapada y a la vez congelándome”, contó Kendeffy, una paramédica de 44 años de State College, Pensilvania.Al día siguiente, fue a trabajar y preguntó entre sus colegas —ocho hombres y siete mujeres— acerca de su experiencia con las vacunas. Seis de las mujeres tuvieron dolor de cuerpo, escalofríos y fatiga. La única mujer que no tuvo síntomas de influenza estuvo despierta vomitando gran parte de la noche.Los ocho hombres dieron testimonios muy diferentes. Uno tuvo un ligero dolor en el brazo, dolor de cabeza y dolor corporal. Dos hablaron de una ligera fatiga y un poco de dolor muscular. Uno tuvo dolor de cabeza. Y cuatro no experimentaron ningún síntoma.“Yo trabajo con mujeres muy fuertes”, afirmó Kendeffy. Pero dijo: “es evidente que, para nosotras, los efectos secundarios fueron más intensos”. Después de 24 horas, ya se sintió mejor y está muy contenta de haber recibido la vacuna. “No me arrepiento, porque seguro que esto es mejor que la alternativa”, señaló. “Pero tampoco sabía qué esperar”.Las diferencias que Kendeffy observó entre sus colegas están apareciendo en todo el país. En un estudio publicado el mes pasado, los investigadores de los Centros para el Control y la Prevención de Enfermedades (CDC, por su sigla en inglés) analizaron los datos de inocuidad de los primeros 13,7 millones de dosis de vacunas contra la COVID-19 administradas a los estadounidenses. De los efectos secundarios reportados a este organismo, el 79,1 por ciento vino de mujeres, pese a que solo habían aplicado el 61,2 por ciento de las vacunas a personas del sexo femenino.La mayor parte de las insólitas reacciones anafilácticas a las vacunas contra el coronavirus también se han presentado en mujeres. Los investigadores de los CDC informaron que los 19 sujetos que habían sufrido esa reacción a la vacuna de Moderna eran mujeres y que las mujeres representaban 44 de los 47 sujetos que han tenido reacciones anafilácticas a la vacuna de Pfizer.“No me sorprende en absoluto”, señaló Sabra Klein, microbióloga e inmunóloga de la Escuela de Salud Pública Bloomberg de la Universidad Johns Hopkins. “La diferencia que se da según el sexo coincide por completo con informes anteriores relacionados con otras vacunas”.En un estudio de 2013, los científicos de los CDC y de otras instituciones descubrieron que cuatro veces más mujeres que hombres entre 20 y 59 años reportaron reacciones alérgicas después de recibir la vacuna de 2009 contra la influenza, pese a que fueron vacunados más hombres que mujeres. En otro estudio, se descubrió que entre 1990 y 2016, las mujeres conformaron el 80 por ciento de todos los casos de reacciones anafilácticas a las vacunas en personas adultas.En general, las mujeres “tienen más reacciones a una diversidad de vacunas”, mencionó Julianne Gee, funcionaria médica en la Oficina de Seguridad de la Inmunización de los CDC. Eso incluye las vacunas contra la influenza que se administran a los adultos, así como algunas que se administran en la infancia, como las vacunas contra la hepatitis B y la de sarampión, rubeóla y paperas (SRP).Sin embargo, la noticia no es tan mala para las mujeres. Casi siempre, los efectos secundarios son leves y de poca duración. Además, estas reacciones físicas son una señal de que la vacuna está surtiendo efecto, de que estás “desarrollando una respuesta inmunitaria muy consistente y es probable que, como consecuencia” estés “protegida”, señaló Klein.Así avanza la vacunación en el mundoTracking Coronavirus Vaccinations Around the WorldMore than 316.6 million vaccine doses have been administered worldwide, equal to 4.1 doses for every 100 people.¿Pero por qué se dan estas diferencias según el sexo? Parte de la respuesta podría ser de comportamientos. Rosemary Morgan, investigadora de salud a nivel internacional de la Escuela de Salud Pública Bloomberg de la Universidad Johns Hopkins dijo que es posible que las mujeres hablen de efectos secundarios más que los hombres incluso cuando sus síntomas sean los mismos. No existe ninguna investigación específica sobre las vacunas que respalde esta aseveración, pero es menos probable que los varones consulten a un médico cuando están enfermos, así que quizás sea menos probable que reporten efectos secundarios, comentó.Sin embargo, no hay duda de que la biología tiene una participación importante. “De muchos modos, la respuesta inmunitaria de las mujeres es distinta a la de los hombres”, señaló Eleanor Fish, inmunóloga de la Universidad de Toronto.Las investigaciones han demostrado que, en comparación con sus contrapartes masculinos, las mujeres y las niñas producen más anticuerpos que combaten las infecciones —en ocasiones hasta el doble— como respuesta a las vacunas contra la influenza, SPR, fiebre amarilla, rabia, así como hepatitis A y B. Gee mencionó que también a menudo desarrollan respuestas más consistentes que vienen de las células inmunitarias llamadas células T. La mayor parte de las veces, estas diferencias son más importantes en adultos jóvenes, lo cual “nos habla de un efecto biológico que tal vez esté relacionado con las hormonas de la reproducción”, señaló.Las hormonas sexuales que incluyen los estrógenos, la progesterona y la testosterona pueden adherirse a la superficie de las células inmunitarias e influir en la manera en que funcionan. Por ejemplo, la exposición a los estrógenos hace que las células inmunitarias produzcan más anticuerpos como repuesta a la vacuna contra la influenza.Además, según Klein, la testosterona “parece ser muy inmunosupresora”. La vacuna contra la influenza tiende a ser menos protectora en los varones que tienen mucha testosterona, en comparación con los que tienen una menor cantidad de esa hormona sexual. Entre otras cosas, la testosterona inhibe la producción de sustancias químicas inmunitarias, conocidas como citoquinas, que realiza el cuerpo.También es posible que las diferencias genéticas entre hombres y mujeres tengan alguna influencia sobre la inmunidad. Muchos genes relacionados con la inmunidad se encuentran en el cromosoma X, del cual las mujeres tienen dos copias y los hombres solo una. Los inmunólogos siempre han creído que solo se encendió un cromosoma X en las mujeres y que el otro estaba inactivo. Pero ahora, las investigaciones demuestran que el 15 por ciento de los genes eluden esta inactivación y se expresan más en las mujeres.Estas fuertes respuestas inmunitarias ayudan a explicar por qué el 80 por ciento de las enfermedades autoinmunes afecta a las mujeres. “Las mujeres poseemos una mayor inmunidad, ya sea hacia nosotras mismas, hacia un antígeno vacunal o hacia un virus”, afirmó Klein.También puede ser importante la cantidad que contiene una dosis de la vacuna. En algunos estudios, se ha demostrado que las mujeres absorben y metabolizan los medicamentos de una manera distinta a la de los varones y que casi siempre requieren menos dosis para que estos surtan el mismo efecto. Pero hasta la década de 1990, en gran parte de los ensayos clínicos para fármacos y vacunas se excluía a las mujeres. “Desde siempre, las dosis recomendadas de los medicamentos se basan en ensayos clínicos en los que los participantes son hombres”, señaló Morgan.Los ensayos clínicos actuales ya incluyen a las mujeres. Pero, según Klein, en los ensayos para las nuevas vacunas contra la covid, no se distinguieron ni se analizaron lo suficiente los efectos secundarios por sexo. Tampoco probaron si una dosis más pequeña podría ser igualmente eficaz para las mujeres y producirles menos efectos secundarios.Hasta que no lo hagan, comentó Klein, los profesionales de la salud deben hablar con las mujeres sobre los efectos secundarios de las vacunas para que no se asusten si los presentan. “Creo que es útil alertar a las mujeres de que quizás tengan más reacciones adversas”, afirmó. “Eso es normal y es probable que sea un reflejo de que su sistema inmunitario está funcionando”.Vacunas contra la COVID-19: respondemos todas tus dudasLos periodistas del Times respondieron a las preguntas de los lectores sobre la vacunación, qué podemos esperar y lo que va a pasar ahora.AdvertisementContinue reading the main story

Aspirin is an established, safe, and low-cost medication in long-standing common use in prevention and treatment of cardiovascular diseases, and in the past a pain relief and fever reducing medication. The use of aspirin was very popular during the 1918 Spanish Influenza pandemic, several decades before in-vitro confirmation of its activity against RNA viruses. Studies showed that aspirin, in addition to its well-known anti-inflammatory effects, could modulate the innate and adaptive immune responses helping the human immune system battle some viral infections.
With this information in mind Israeli researchers hypothesized that pre-infection treatment with low-dose aspirin (75mg) use might have a potential beneficial effect on COVID-19 susceptibility and disease duration. A joint team from Leumit Health Services, Bar-Ilan University, and Barzilai Medical Center conducted an observational epidemiological study, utilizing data from Leumit Health Services, a national health maintenance organization in Israel. Their findings were recently published in The FEBS Journal.
The researchers analyzed data of 10,477 persons who had been tested for COVID-19 during the first COVID-19 wave in Israel from February 1, 2020 to June 30, 2020. Aspirin use to avoid the development of cardiovascular diseases in healthy individuals was associated with a 29% lower likelihood of COVID-19 infection, as compared to aspirin non-users. The proportion of patients treated with aspirin was significantly lower among the COVID-19-positive individuals, as compared to the COVID-19-negative ones. And those subjects who had been treated with aspirin were less associated with the likelihood of COVID-19 infection than those who were not. Moreover, the group observed that the conversion time of SARS-CoV-2 PCR test results from positive to negative among aspirin-using COVID-positive patients was significantly shorter, and the disease duration was two-three days shorter, depending upon the patients’ pre-existing conditions.
“This observation of the possible beneficial effect of low doses of aspirin on COVID-19 infection is preliminary but seems very promising,” says Prof. Eli Magen from the Barzilai Medical Center, who led the study.
Study principal investigator Dr. Eugene Merzon, from Leumit Health Services, emphasizes the importance of repeating the study results using larger samples, and including patients from other hospitals and countries, to verify the results.
Dr. Milana Frenkel-Morgenstern, of the Azrieli Faculty of Medicine of Bar-Ilan University: “The present study sought to better understand the potential favorable effects of aspirin in aiding the human immune system battle COVID-19. We intend to investigate a larger cohort of patients and in randomized clinical trials.”

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A gene therapy for chronic pain could offer a safer, non-addictive alternative to opioids. Researchers at the University of California San Diego developed the new therapy, which works by temporarily repressing a gene involved in sensing pain. It increased pain tolerance in mice, lowered their sensitivity to pain and provided months of pain relief without causing numbness.
The researchers report their findings in a paper published Mar. 10 in Science Translational Medicine.
The gene therapy could be used to treat a broad range of chronic pain conditions, from lower back pain to rare neuropathic pain disorders — conditions for which opioid painkillers are the current standard of care.
“What we have right now does not work,” said first author Ana Moreno, a bioengineering alumna from the UC San Diego Jacobs School of Engineering. Opioids can make people more sensitive to pain over time, leading them to rely on increasingly higher doses. “There’s a desperate need for a treatment that’s effective, long-lasting and non-addictive.”
The idea for such a treatment emerged when Moreno was a Ph.D. student in UC San Diego bioengineering professor Prashant Mali’s lab. Mali had been investigating the possibility of applying CRISPR-based gene therapy approaches to rare as well as common human diseases. Moreno’s project focused on exploring potential therapeutic avenues. One day, she came across a paper about a genetic mutation that causes humans to feel no pain. This mutation inactivates a protein in pain-transmitting neurons in the spinal cord, called NaV1.7. In individuals lacking functional NaV1.7, sensations like touching something hot or sharp do not register as pain. On the other hand, a gene mutation that leads to overexpression of NaV1.7 causes individuals to feel more pain.
When Moreno read this, it clicked. “By targeting this gene, we could alter the pain phenotype,” she said. “What’s also cool is that this gene is only involved in pain. There aren’t any severe side effects observed with this mutation.”
Non-permanent gene therapy

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Moreno had been working on gene repression using the CRISPR gene editing tool as part of her dissertation. Specifically, she was working with a version of CRISPR that uses what’s called “dead” Cas9, which lacks the ability to cut DNA. Instead, it sticks to a gene target and blocks its expression.
Moreno saw an opportunity to use this approach to repress the gene that codes for NaV1.7. She points out an appeal of this approach: “It’s not cutting out any genes, so there are no permanent changes to the genome. You wouldn’t want to permanently lose the ability to feel pain,” she said. “One of the biggest concerns with CRISPR gene editing is off-target effects. Once you cut DNA, that’s it. You can’t go back. With dead Cas9, we’re not doing something irreversible.”
Mali, who is a co-senior author of the study, says that this use of dead Cas9 opens the door to using gene therapy to target common diseases and chronic ailments.
“In some common diseases, the issue is that a gene is being misexpressed. You don’t want to completely shut it down,” he said. “But if you could turn down the dose of that gene, you could bring it to a level where it is not pathogenic. That is what we are doing here. We don’t completely take away the pain phenotype, we dampen it.”
Moreno and Mali co-founded the spinoff company Navega Therapeutics to work on translating this gene therapy approach, which they developed at UC San Diego, into the clinic. They teamed up with Tony Yaksh, an expert in pain systems and a professor of anesthesiology and pharmacology at UC San Diego School of Medicine. Yaksh is a scientific advisor to Navega and co-senior author of the study.

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Early lab studies
The researchers engineered a CRISPR/dead Cas9 system to target and repress the gene that codes for NaV1.7. They administered spinal injections of their system to mice with inflammatory and chemotherapy-induced pain. These mice displayed higher pain thresholds than mice that did not receive the gene therapy; they were slower to withdraw a paw from painful stimuli (heat, cold or pressure) and spent less time licking or shaking it after being hurt.
The treatment was tested at various timepoints. It was still effective after 44 weeks in the mice with inflammatory pain and 15 weeks in those with chemotherapy-induced pain. The length of duration is still being tested, researchers said, and is expected to be long-lasting. Moreover, the treated mice did not lose sensitivity or display any changes in normal motor function.
To validate their results, the researchers performed the same tests using another gene editing tool called zinc finger proteins. It’s an older technique than CRISPR, but it does the same job. Here, the researchers designed zinc fingers that similarly bind to the gene target and block expression of NaV1.7. Spinal injections of the zinc fingers in mice produced the same results as the CRISPR-dead Cas9 system.
“We were excited that both approaches worked,” Mali said. “The beauty about zinc finger proteins is that they are built on the scaffold of a human protein. The CRISPR system is a foreign protein that comes from bacteria, so it could cause an immune response. That’s why we explored zinc fingers as well, so we have an option that might be more translatable to the clinic.”
The researchers say this solution could work for a large number of chronic pain conditions arising from increased expression of NaV1.7, including diabetic polyneuropathy, erythromelalgia, sciatica and osteoarthritis. It could also provide relief for patients undergoing chemotherapy.
And due to its non-permanent effects, this therapeutic platform could address a poorly met need for a large population of patients with long-lasting (weeks to months) but reversible pain conditions, Yaksh said.
“Think of the young athlete or wounded war fighter in which the pain may resolve with wound healing,” he said. “We would not want to permanently remove the ability to sense pain in these people, especially if they have a long life expectancy. This CRISPR/dead Cas9 approach offers this population an alternative therapeutic intervention — that’s a major step in the field of pain management.”
Researchers at UC San Diego and Navega will next work on optimizing both approaches (CRISPR and zinc fingers) for targeting the human gene that codes for NaV1.7. Trials in non-human primates to test for efficacy and toxicity will follow. Researchers expect to file for an IND and to commence human clinical trials in a couple years.
This work was supported by UC San Diego Institutional Funds and the National Institutes of Health (grants R01HG009285, RO1CA222826, RO1GM123313, R43CA239940, R43NS112088, R01NS102432, R01NS099338).
Disclosure: Ana Moreno, Fernando Alemán, Prashant Mali and Tony Yaksh have a financial interest in Navega Therapeutics. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.

A new systematic review of 65 studies from around the world involves a total of 97,333 health care workers and finds that 1 in 5 have experienced depression, anxiety, and/or PTSD during the ongoing COVID-19 pandemic. Yufei Li, Nathaniel Scherer, and colleagues at the London School of Hygiene & Tropical Medicine, U.K., present these findings in the open-access journal PLOS ONE on March 10.
The pandemic has posed significant challenges for health care workers, with many fearing for their own safety while facing a high workload and limited psychological support. Previous analyses of data from multiple studies have revealed high rates of depression, anxiety, and PTSD among health care workers during the pandemic. However, those reviews did not adequately address the many relevant studies conducted in China, where the first COVID-19 outbreak occurred.
To address that gap, Li, Scherer, and colleagues carried out a systematic search of studies in both English and Chinese that were conducted from December 2019 to August 2020 and addressed prevalence of mental disorders in health care workers. They identified 65 suitable studies from 21 countries, involving a total of 97,333 health care workers.
By pooling and statistically analyzing data from all 65 studies, the researchers estimated that 21.7 percent of the health care workers involved in the studies have experienced depression during the pandemic, 22.1 percent anxiety, and 21.5 percent PTSD. Studies conducted in the Middle East showed the highest pooled rates of depression (34.6 percent) and anxiety (28.9 percent).
These findings suggest that the COVID-19 pandemic has significantly impacted the mental health of health care workers. For comparison, the World Health Organization estimates that 4.4 percent of the entire world population experience depression, and 3.6 percent experience anxiety disorders, including PTSD. However, those estimates were determined through different methods and prior to the pandemic.
Nonetheless, the authors note, the new findings could help inform policy and initiatives to provide urgently needed psychological support to health care workers.
The authors add: “This systematic review and meta-analysis provides, to date, the most comprehensive synthesis of depression, anxiety and PTSD prevalence amongst health care workers during the COVID-19 pandemic, with the unique inclusion of publications in both English and Chinese.”

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UT Southwestern scientists have identified key genes involved in brain waves that are pivotal for encoding memories. The findings, published online this week in Nature Neuroscience, could eventually be used to develop novel therapies for people with memory loss disorders such as Alzheimer’s disease and other forms of dementia.
Making a memory involves groups of brain cells firing cooperatively at various frequencies, a phenomenon known as neural oscillations. However, explain study leaders Bradley C. Lega, M.D., associate professor of neurological surgery, neurology, and psychiatry, and Genevieve Konopka, Ph.D., associate professor of neuroscience, the genetic basis of this process is not clear.
“There’s a famous saying for 100 years in neuroscience: Neurons that fire together will wire together,” says Lega. “We know that cells involved in learning fire in groups and form new connections because of the influence of these oscillations. But how genes regulate this process in people is completely unknown.”
Lega and Konopka, both members of the Peter O’Donnell Jr. Brain Institute, collaborated on a previous study to explore this question, collecting data on neural oscillations from volunteers and using statistical methods to connect this information to data on gene activity collected from postmortem brains. Although these results identified a promising list of genes, Konopka says, there was a significant shortcoming in the research: The oscillation and genetic data came from different sets of individuals.
More recently, the duo capitalized on an unprecedented opportunity — performing a similar study on patients undergoing surgeries in which damaged parts of their brains were removed to help control their epilepsy.
The researchers worked with 16 volunteers from UT Southwestern’s Epilepsy Monitoring Unit, where epilepsy patients stay for several days before having surgery to remove the damaged parts of their brains that spark seizures. Electrodes implanted in these patients’ brains over this time not only help their surgeons precisely identify the focus of the seizure, Lega says, but can also provide valuable information on the brain’s inner workings.

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While recording the electrical activity in the brains of 16 volunteers, the researchers had them do “free recall” tasks that involved reading a list of 12 words, doing a short math problem to distract them, and then recalling as many words as possible. As these patients were memorizing the word lists, their brain waves were recorded, creating a dataset that differed slightly from person to person.
About six weeks later, each volunteer underwent a temporal lobectomy — removal of the brain’s temporal lobe — to cure their seizures. This area frequently serves as an originator of epileptic seizures and is also important for memory formation. Within five minutes of the surgery, the damaged brain tissue was sent for processing to assess genetic activity.
Konopka’s team first performed whole RNA sequencing, a technique that identifies active genes, in temporal lobe samples that included all the brain’s cell types. Using statistical techniques that linked this activity to the patients’ neural oscillations during the free recall task, the researchers identified 300 genes that appeared to play a part in oscillatory activity. The researchers narrowed this number to a dozen “hub genes” that appeared to control separate gene networks.
Next, the researchers looked at the activity of these hub genes in separate cell types within the samples. Surprisingly, they found that several of these hubs weren’t active within nerve cells themselves but in a different population of cells known as glia. These cells provide support and protection for nerve cells, including manufacturing the fatty layer that insulates nerve cells so they can efficiently pass electrical signals.
Finally, the researchers used a technique called ATAC-seq, which identifies areas of DNA that are open for molecules called transcription factors to attach to and activate genes. Using this approach, they honed in on SMAD3, a gene that appears to serve as a master regulator to control activity of many of the hub genes and the genes they control in return.
Konopka and Lega note that several of the genes they identified as important in human neural oscillations have been linked to other disorders that can affect learning and memory, such as autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, and schizophrenia. With further research into these genes and the networks they operate within, it may eventually be possible to target select genes with pharmaceuticals to improve memory in individuals with these and other conditions, the researchers say.
“This gives us an entry point,” says Konopka, a Jon Heighten Scholar in Autism Research. “It’s something we can focus on to learn more about the underpinnings of human memory.”
This work was supported by the National Institute of Mental Health (F30MH105158 and MH103517), National Institute on Drug Abuse (5T32DA007290-25), National Heart, Lung, and Blood Institute (1T32HL139438-01A1); National Institute of Neurological Disorders and Stroke (NS106447 and NS107357), a UT BRAIN Initiative Seed Grant (366582), the Chilton Foundation, the National Center for Advancing Translational Sciences of the NIH under the Center for Translational Medicine’s award number UL1TR001105, The Chan Zuckerberg Initiative, an advised fund of Silicon Valley Community Foundation (HCA-A-1704-01747), and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition — Scholar Award.

The mosquito protein AEG12 strongly inhibits the family of viruses that cause yellow fever, dengue, West Nile, and Zika and weakly inhibits coronaviruses, according to scientists at the National Institutes of Health (NIH) and their collaborators. The researchers found that AEG12 works by destabilizing the viral envelope, breaking its protective covering. Although the protein does not affect viruses that do not have an envelope, such as those that cause pink eye and bladder infections, the findings could lead to therapeutics against viruses that affect millions of people around the world. The research was published online in PNAS.
Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, used X-ray crystallography to solve the structure of AEG12. Senior author Geoffrey Mueller, Ph.D., head of the NIEHS Nuclear Magnetic Resonance Group, said at the molecular level, AEG12 rips out the lipids, or the fat-like portions of the membrane that hold the virus together.
“It is as if AEG12 is hungry for the lipids that are in the virus membrane, so it gets rid of some of the lipids it has and exchanges them for the ones it really prefers,” Mueller said. “The protein has high affinity for viral lipids and steals them from the virus.”
As a result, Mueller says the AEG12 protein has great killing power over some viruses. While the researchers demonstrated that AEG12 was most effective against flaviviruses, the family of viruses to which Zika, West Nile, and others belong, it is possible AEG12 could be effective against SARS-CoV-2, the coronavirus that causes COVID-19. But, Mueller said it will take years of bioengineering to make AEG12 a viable therapy for COVID-19. Part of the problem is AEG12 also breaks opens red blood cells, so researchers will have to identify compounds that will make the protein target viruses only.
Alexander Foo, Ph.D., an NIEHS visiting fellow and lead author of the paper, explained that mosquitoes produce AEG12 when they take a blood meal or become infected with flaviviruses. Like humans, mosquitoes mount a vigorous immune response against these viruses, with AEG12 bursting their viral covering. But, at the beginning of the project, Foo and his colleagues knew little about the function of AEG12.
“The prospect of studying a new protein is exciting, yet daunting,” Foo said. “Thankfully, we had enough clues and access to a wide range of expertise at NIEHS to piece it together.”
Co-author and crystallography expert Lars Pedersen, Ph.D., is leader of the NIEHS Structure Function Group. He routinely uses information about a molecule’s physical makeup in his work and encourages more scientists to consider using this data in their studies. He said, “Our research shows that understanding the structure of a protein can be important in figuring out what it does and how it could help treat disease.”

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How One Church is Vaccinating the NeighborhoodSimbarashe Cha for The New York TimesThe Rev. Dr. Calvin O. Butts III rolled his sleeve up last month as he got vaccinated in front of cameras to show that the coronavirus vaccine is safe. I spent the day with him as his church, Abyssinian Baptist, vaccinated others. Here is what else I saw →

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesUK scientists have discovered a key inflammatory protein that rises in the blood of patients with severe Covid-19.The protein – known as GM-CSF – was found to be nearly 10 times higher in patients who went on to die from the virus. Scientists say that with further research, the protein could help identify those most at risk and provide clues for better targeted treatments for the disease. The work appears in Science Immunology.Researchers analysed blood samples from 470 patients admitted to hospital with Covid-19 in the UK, comparing them with samples from people with mild coronavirus, healthy people and stored samples from people who had previously had swine flu.They found several inflammatory proteins – part of the body’s immune response – were raised in people who were ill, but only GM-CSF was specific to severe Covid-19.Scientists are concerned that while some of these inflammatory proteins help the body fight off the illness, others may do more harm than good by damaging organs.Dr Kenneth Baillie, at the University of Edinburgh, said: “By studying patients with severe Covid-19 at large scale across the UK, we’re building a clearer picture of lung disease in Covid-19.”The lungs are being damaged by the patient’s own immune system rather than directly being damaged by the virus, and we can see specific signals in the immune system that might be responsible.”Researchers say further work will help them understand whether inflammatory proteins like GM-CSF are one of the factors driving severe disease, and whether dampening these proteins with specific drugs can help. Professor Peter Openshaw, of Imperial College London, said he hoped ultimately that the work would help find treatments that were more precise than some current therapies. He added: “The future that we all want to embrace is one in which instead of giving very broad acting, rather poorly understood immunosuppressive treatments like steroids, that we can actually begin to pinpoint some therapy that just takes out the specific pathway that is causing harm whilst allowing the rest of the immune system to continue to do its job of clearing out the virus and restoring health.”Several drugs that target GM-CSF are being trialled but none have yet been approved for use. OXFORD JAB: What is the Oxford-AstraZeneca vaccine?YOUR QUESTIONS: We answer your queriesVACCINE: When will I get the jab?COVID IMMUNITY: Can you catch it twice?LOCKDOWN TIPS: Five ways to stay positiveRelated Internet LinksISARIC4C consortium.websiteScience Immunology.websiteThe BBC is not responsible for the content of external sites.

Scientists and healthcare providers are beginning to use a new approach for assessing a person’s inherited risk for diseases like Type 2 diabetes, coronary heart disease and breast cancer, which involves calculating a polygenic risk score. The score provides an estimate of an individual’s risk for specific diseases, based on their DNA changes related to those diseases.
Despite the rise in studies using polygenic risk scores, researchers have observed inconsistencies in how such scores are calculated and reported. These differences threaten to compromise the adoption of polygenic risk scores in clinical care.
To address this concern, the research teams, funded primarily by the National Human Genome Research Institute (NHGRI), have published a 22-item framework in the journal Nature that identifies the minimal polygenic risk score-related information that scientists should include in their studies. This framework — created by NHGRI’s Clinical Genome Resource’s (ClinGen) Complex Disease Working Group and the Polygenic Score Catalog (PGS), an open database of polygenic risk scores — will help promote the validity, transparency and reproducibility of polygenic risk scores. NHGRI is part of the National Institutes of Health.
To calculate a person’s polygenic risk score, researchers survey DNA variants in over 6 billion locations in the human genome.
“A real challenge is that the research community has not adopted any universal best practices for reporting polygenic risk scores,” said Erin Ramos, Ph.D., a program director for ClinGen, deputy director of the NHGRI Division of Genomic Medicine and co-author of the paper. “With the field growing as fast as it is, we need standards in place so we can meaningfully evaluate these scores and determine which ones are ready to be used in clinical care.”
This framework builds off another best practice model called the Genetic Risk Prediction Studies (GRIPS) statement, published by an international working group in 2011. GRIPS placed an emphasis on models that included a smaller set of genomic variants and gene scores. However, genetic risk prediction models have evolved rapidly since then, and are based on a much larger set of genomic variants and more complex methodologies. Also, researchers have not fully adopted the GRIPS framework.
“A renewed emphasis on reporting standards by ClinGen and the Polygenic Score Catalog comes at a crucial time for polygenic risk scores,” said Genevieve Wojcik, Ph.D., M.H.S., an assistant professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and corresponding author of the paper. “It specifies the minimum information that should be described in a research paper for interpreting a polygenic risk score, reproducing results and eventually translating the information into clinical care.”
Some of the new reporting framework items include detailing the study population and the basis for choosing that population.
“If we are to make these scores available to people around the world, the studies need to define who they are studying and why, in the clearest way possible,” said Katrina Goddard, Ph.D., director of Translational and Applied Genomics at the Kaiser Permanente Center for Health Research, Portland, Oregon, who also co-authored the paper. “Without that transparency and reproducibility, efforts to use polygenic risk scores may be undermined.”
The new framework suggests that scientists should explain the statistical methods they used to develop and validate the polygenic risk scores. Without a consistent way of reporting polygenic risk scores, it is nearly impossible to compare the utility of the scores for assessing disease risk in people. According to the new guidelines, researchers should also consider potential limitations of these scores and how clinicians should use the scores in patient care.
“If researchers can follow these guidelines, it will be more straightforward to evaluate published polygenic risk scores and decide which ones are a good fit for the clinical setting,” said Michael Inouye, Ph.D., director of the Cambridge Baker Systems Genomics Initiative, U.K., and co-senior author of the paper. “For diseases such as breast cancer and many others, we will be able to responsibly place patients in different risk categories and provide beneficial screening strategies and treatments. Ideally, in the future, we will detect risk early enough to combat the disease effectively.”