Body

WEST LAFAYETTE, Ind. - The COVID-19 pandemic is leading a Purdue University innovator to make changes as she works to provide new options for people with Parkinson's disease.

Jessica Huber, a professor of Speech, Language, and Hearing Sciences and associate dean for research in Purdue's College of Health and Human Sciences, leads Purdue's Motor Speech Lab. Huber and her team are now doing virtual studies to evaluate speech disorders related to Parkinson's using artificial intelligence technology platforms.

Huber and her team have been working to develop telepractice tools for the assessment and treatment of speech impairments like Parkinson's disease. They received a National Institutes of Health small business innovation and research grant to develop a telehealth platform to facilitate the provision of speech treatment with the SpeechVive device, which has received attention at the Annual Convention of the American Speech-Language-Hearing Association.

In the current study, Huber and her team are collaborating with a startup company, Modality AI, which developed the AI platform that will be used in the study.

"The application of the technology we are evaluating may lead to far-reaching insights into more standardization in assessments, earlier diagnoses and possibly an easier way to track discrete changes over time to guide interventions," said Andrew Exner, a graduate research assistant in the Motor Speech Lab. "My personal research passion, and the mission of our lab, is to find ways to improve the quality of life for people with Parkinson's and other related diseases."

Exner is leading the virtual study for participants across the country to evaluate an AI platform that can collect and automatically measure the speech skills of people with Parkinson's disease. The need for AI platforms is increasing as the use of telepractice explodes as a result of the COVID-19 pandemic.

"My interest in speech-language pathology actually started during my training as an actor and opera singer," Exner said. "I saw the effects of pathology on the voice and wanted to extend that interest into speech disorders."

SpeechVive Inc. is an Indiana startup company based on Huber's research. The company has developed a wearable medical device to improve the speech clarity of people with Parkinson's.

Aortic stenosis is one of the most common heart valve defects. Its prevalence increases with age and it often requires treatment. As well as conventional valve replacement involving open-heart surgery, a less invasive procedure has now been available for some time in the form of transcatheter aortic valve replacement (TAVR). In this procedure, the new valve is implanted during a cardiac catheter examination. This minimally invasive procedure is an important treatment option, especially for older patients.

Up until now, it was not clear whether patients with an additional condition, cardiac amyloidosis, would also benefit from a valve replacement. In this heart condition, amyloid protein deposits cause the heart muscle to thicken and harden. As a result, the heart is no longer able to contract and expand evenly, so that the blood supply to the body is compromised.

The recent study looked at the coincidence of both diseases in aortic stenosis patients referred for a TAVR procedure, as well as any prognostic implication. Overall, cardiac amyloidosis was detected in one in eight of the 407 aortic stenosis patients examined. Since it is not economically or logistically feasible to carry out a DPD bone scintigraphy scan (a sensitive test to identify cardiac amyloidosis) on all TAVR patients, the study team developed a scoring system based on simple clinical parameters to screen for dual heart disease.

"The scoring system enables us to use simple clinical parameters such as ECG changes, above-average cardiac hypertrophy or existing or operated carpal tunnel syndrome, to predict the probability of concomitant cardiac amyloidosis in aortic stenosis patients, so that they require further investigation using DPD bone scintigraphy," says lead investigator Christian Nitsche from the Division of Cardiology, Department of Medicine II of MedUni Vienna and Vienna General Hospital.

The study published in the Journal of the American College of Cardiology also found that both aortic stenosis patients with concomitant cardiac amyloidosis and those without this additional heart disease benefit from TAVR. "The results show that the minimally invasive TAVR technique is suitable for both groups. We therefore conclude that TAVR should not be withheld from aortic stenosis patients who also suffer from cardiac amyloidosis," says Nitsche.

Further studies are required to determine whether the drugs used to treat cardiac amyloidosis improve survival in dual heart disease on top of aortic valve replacement.

CHICAGO (November 23, 2020): The Affordable Care Act's Medicaid expansion for low-income people appears to lead to earlier diagnosis of colon cancer, enhanced access to care, and improved surgical care for patients with this common cancer, researchers report in a new study. The study is published as an "article in press" on the Journal of the American College of Surgeons website in advance of print.

In states that expanded Medicaid health insurance coverage in 2014, the study authors reported an increase of early-stage colon cancer diagnoses compared with states that did not implement Medicaid expansion. More surgical patients from states with Medicaid expansion had minimally invasive surgical procedures, and fewer patients underwent urgent operations than in states not implementing expansion, said lead author Richard S. Hoehn, MD, surgical oncology fellow with the University of Pittsburgh Medical Center (UPMC) department of surgery at UPMC Hillman Cancer Center, Pittsburgh, Pa.

"A paucity of studies looks at how Medicaid expansion affects cancer treatment and outcomes, as our study did," Dr. Hoehn said. "Our study also differed from others in that we analyzed data only from people who were most likely affected by Medicaid expansion: those aged 40 to 64 who had Medicaid or no health insurance."

Medicaid expansion, which took effect January 1, 2014, extended this public health insurance coverage to more low-income people.1 Initially, 19 states did not implement Medicaid expansion, but to date, all but 12 states have adopted the expansion.1

Access to health care may be especially important for colon cancer, the authors wrote in their article. Colon and rectal cancer is the fourth most common cancer in the United States and is increasing among adults younger than age 652--those not yet eligible for Medicare, the country's public health insurance for seniors. Despite the availability of colonoscopy to screen for colorectal cancer, the American Cancer Society reports that one in three Americans who should receive this screening do not, for reasons including inadequate health insurance.3

The researchers used data on invasive colon cancer collected in the National Cancer Database (NCDB), the largest cancer registry of its kind. Cosponsored by the American College of Surgeons and the American Cancer Society, the NCDB includes information on more than 70 percent of newly diagnosed cancer cases in the U.S.

Dr. Hoehn and his colleagues compared colon cancer data for 4,438 patients residing in 19 states that implemented expansion in January 2014 ("expansion states") with data for 6,017 patients in 19 "nonexpansion" states at that time. To estimate the relative effect of the expansion policy, they selected the years 2011-2012 to assess data before expansion and 2015-2016 for post-expansion data.

In statistical analyses between these periods, the investigators observed no significant differences between Medicaid expansion and nonexpansion states for postoperative outcomes such as hospital length of stay, readmission rates, and deaths. However, patients with colon cancer stages I to III did have differences in timeliness of care based on their state expansion category. In nonexpansion states, the days to treatment (primarily surgical) increased and the proportion of patients treated in less than 30 days decreased. Dr. Hoehn said they did not observe these delays in care in expansion states.

Other key differences in the 2015-2016 period were as follows:

A larger number of patients in expansion states received treatment at integrated network cancer programs accredited by the Commission on Cancer of the American College of Surgeons. Research evidence for other cancer types suggests these programs offer better overall survival rates.4,5

Patients traveled farther for care in expansion states, suggesting that patients who lived greater distances from hospitals could now obtain care because of coverage, Dr. Hoehn noted.
Patients in expansion states who had end-stage colon cancer were more likely to receive palliative care services, which aim to improve quality of life.
Among patients who underwent cancer operations, more in expansion states had minimally invasive surgery and nonurgent operations. Dr. Hoehn said both changes may be due to earlier diagnosis in these states.

The reasons why patients in expansion states had more stage I diagnoses after expansion than before are unclear from the data but may point to better access to care, said senior investigator Samer T. Tohme, MD, surgical oncologist at UPMC Hillman Cancer Center and assistant professor of surgery at the University of Pittsburgh School of Medicine. He said their findings suggest that Medicaid expansion has enabled more previously uninsured people to see a primary care physician and get screened for colon cancer.

"Studies show that patients who are diagnosed with cancer at an earlier stage are more likely to have better treatment options, improved quality of care, and longer survival," Dr. Tohme said.

Their study, however, did not track survival rates or other long-term results.

Dr. Hoehn said it is important to study the impact of expanded health insurance coverage.

"Studies like ours are building an increasing body of work that suggests the Affordable Care Act and Medicaid expansion are improving health care access and treatment for cancer patients," he said.

Abnormally high blood sugar may worsen outcomes and mortality rates for COVID-19 patients, including those without diabetes, according to major research published in the peer-reviewed open access journal Annals of Medicine.

The study, based on more than 11,000 non-critically ill hospital patients in Spain, is the largest of its kind to date. It adds to evidence that hyperglycaemia - the medical term for high blood glucose - is associated with a higher chance of death independent of a diabetes diagnosis.

The findings show patients with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% compared to 15.7%). They also had an increased need for a ventilator and intensive care admission (ICU).

The researchers are now calling for compulsory hyperglycemia screening and early treatment for anyone hospitalized with COVID-19 who is non-diabetic. They urge clinicians not to overlook the condition among patients, regardless of a prior history of diabetes.

"Screening for hyperglycaemia in patients without diabetes and early treatment should be mandatory in the management of patients hospitalized with COVID-19," says study coordinator Dr Javier Carrasco from Juan Ramon Jimenez University Hospital.

"Admission hyperglycaemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes."

Hyperglycaemia is a common problem for diabetics but can also be triggered by illness or injury. Studies have previously linked acute cases with complications in diabetic and non-diabetic hospital patients, and observed similar associations among people with COVID-19.

In this study, the aim was to investigate a link between hyperglycaemia and time spent in hospital, mechanical ventilation, ICU admission and mortality, but independent of a diabetes diagnosis.

Data was analyzed from a national registry which has been collating information from more than 100 hospitals in Spain during the pandemic. A total of 11,312 patients were included aged 18 or above who were admitted from March to the end of May.

They were categorized into three groups relating to their blood glucose levels and ranging from normal to high ( 180 mg/dl). A total of 19% had an existing diabetes diagnosis.

The findings showed that patient blood glucose levels as measured on arrival in hospital were independently related to ICU admission, mechanical ventilation and/or death, regardless of diabetes status.

One in five patients died in hospital, with mortality rates highest among those with the greatest blood glucose levels. No difference was found between death rates for those with diabetes and those who did not have the disease.

The authors do caution that most patients did not have their average blood glucose level measured over a period of time. Therefore, some classed as non-diabetic could have had the disease without knowing.

Exactly why hyperglycaemia is linked with higher death rates remains unclear. The researchers say the condition could be another 'inflammatory bystander' or have a more direct effect on how COVID leads to complications and death.

Researchers at Radboud university medical center have discovered an as yet unknown effect of hydroxychloroquine. It inhibits the action of a type of white blood cells important in the first line of defense against infections. Based on this research, hydroxychloroquine is unlikely to be beneficial in clearing viral infections including the new coronavirus SARS-CoV-2, they write in their publication in Cell Reports Medicine.

Hydroxychloroquine is an agent that has been used for years, originally for the treatment of malaria. It is also widely used to treat patients with rheumatic diseases, because hydroxychloroquine has immunomodulatory effects. It is not known exactly how hydroxychloroquine does this. Hydroxychloroquine use for COVID-19 remains a topic of intense debate and investigation. Especially in the context of their use as a prophylaxis, large studies are ongoing to investigate their efficacy.

Rapid action

In a virus infection, such as the new coronavirus SARS-CoV-2, a good response from the immune system is essential for fighting the virus. If the immune response in the beginning of the infection is insufficient, the virus can spread and cause damage. This uncontrolled infection, which sometimes leads to serious illness or death with SARS-CoV-2, is exactly what you want to prevent.

First responders

Raphaël Duivenvoorden, internist-nephrologist at Radboud university medical center, "We looked at the immune response of patients admitted to the hospital with a SARS-CoV-2 infection. We observed that a certain type of immune cells, the monocytes, play an important role in the first line of defense against the coronavirus. Therefore, we investigated the effect of hydroxychloroquine on these cells.

Impaired defense

Monocytes can develop a type of nonspecific memory, something called "trained immunity". Thanks to this mechanism, monocytes are able to develop a stronger response to bacteria and viruses. In this way, monocytes can contribute to a better and earlier control of invaded micro-organisms. Duivenvoorden, who coordinated the study: "We found that hydroxychloroquine prevents the development of this protective mechanism of "trained immunity". That is why we expect hydroxychloroquine to have no beneficial effect on the immune response in a SARS-CoV-2 infection.

TROY, N.Y. - With communities across the nation experiencing a wave of COVID-19 infections, clinicians need effective tools that will enable them to aggressively and accurately treat each patient based on their specific disease presentation, health history, and medical risks.

In research recently published online in Medical Image Analysis, a team of engineers demonstrated how a new algorithm they developed was able to successfully predict whether or not a COVID-19 patient would need ICU intervention. This artificial intelligence-based approach could be a valuable tool in determining a proper course of treatment for individual patients.

The research team, led by Pingkun Yan, an assistant professor of biomedical engineering at Rensselaer Polytechnic Institute, developed this method by combining chest computed tomography (CT) images that assess the severity of a patient’s lung infection with non-imaging data, such as demographic information, vital signs, and laboratory blood test results. By combining these data points, the algorithm is able to predict patient outcomes, specifically whether or not a patient will need ICU intervention.

The algorithm was tested on datasets collected from a total of 295 patients from three different hospitals -- one in the United States, one in Iran, and one in Italy. Researchers were able to compare the algorithm's predictions to what kind of treatment a patient actually ended up needing.

"As a practitioner of AI, I do believe in its power," said Yan, who is a member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer. "It really enables us to analyze a large quantity of data and also extract the features that may not be that obvious to the human eye."

This development is the result of research supported by a recent National Institutes of Health grant, which was awarded to provide solutions during this worldwide pandemic. As the team continues its work, Yan said, researchers will integrate their new algorithm with another that Yan had previously developed to assess a patient's risk of cardiovascular disease using chest CT scans.

"We know that a key factor in COVID mortality is whether a patient has underlying conditions and heart disease is a significant comorbidity," Yan said. "How much this contributes to their disease progress is, right now, fairly subjective. So, we have to have a quantification of their heart condition and then determine how we factor that into this prediction."

“This critical work, led by Professor Yan, offers an actionable solution for clinicians who are in the middle of a worldwide pandemic,” said Deepak Vashishth, the director of CBIS. “This project highlights the capabilities of Rensselaer expertise in bioimaging combined with important partnerships with medical institutions.”

Yan is joined at Rensselaer by Ge Wang, an endowed chair professor of biomedical engineering and member of CBIS, as well as graduate students Hanqing Chao, Xi Fang, and Jiajin Zhang. The Rensselaer team is working in collaboration with Massachusetts General Hospital. When this work is complete, Yan said, the team hopes to translate its algorithm into a method that doctors at Massachusetts General can use to assess their patients.

"We actually are seeing that the impact could go well beyond COVID diseases. For example, patients with other lung diseases," Yan said. "Assessing their heart disease condition, together with their lung condition, could better predict their mortality risk so that we can help them to manage their condition."

The United States' seafood industry declined precipitously in the months following the emergence of the COVID-19 pandemic, and research shows that targeted federal assistance will be necessary to bring it back.

UC Santa Barbara aquaculture and fisheries professor Halley Froehlich and colleagues suspected as much early on in the pandemic, but for something as large and complex as the seafood industry, the trends were not so obvious. As a result, financial assistance in that direction has been slow.

"Seafood is part of the narrative that I would say doesn't get as much attention as something like agriculture," said Froehlich, an author of a study published in the journal Fish and Fisheries. "And that certainly appears to be the case when we're looking at something like the CARES Act, the federal funding source specifically passed to provide economic relief in the U.S."

That is, in large part, due to the fact that policymakers lack sufficient real-time data to see how the seafood industry is faring in the time of lockdowns and social distancing, said the study's lead author, University of Vermont ecologist Easton White.

"One difficulty is that a lot of this data isn't released until months and years later," he said. From the boat to the table, data is generated that must be gathered and processed before it gets released, he explained.

The pandemic is a rapidly evolving situation and the seafood industry can't afford to wait. So, to get a big-picture look at the early effects of COVID-19 on U.S. fisheries and seafood consumption, Froehlich, White and fellow fisheries data experts synthesized multiple sources from across the seafood supply chain, including some unconventional real-time data sets.

"We looked for different indicators of the effects of COVID on seafood and fisheries in general," White said. In addition to federal fisheries reports and customs data, the researchers looked to news reports and Google search trends for seafood and seafood market foot traffic.

Lessons Learned

As had happened for virtually every industry at the start of the pandemic, the lockdowns and closures caused a huge drop in economic activity for the seafood sector, from which many still struggle to recover. Using data from January to September 2020, the researchers calculated a 40% decline in fresh seafood catches, a 37% decline in imports and a 43% drop in exports relative to the same time last year. These impacts are expected to reverberate across the globe, as the U.S. is one of the top exporters and importers of seafood.

Closer to home, demand from restaurants -- the main driver of seafood spending in the U.S. -- virtually disappeared as establishments locked down. Seafood market foot traffic declined steeply as well.

The effects were uneven across fisheries and aquaculture operations.

"Large-scale production systems that have large networks were able to pivot really fast," Froehlich said. "And so if they couldn't sell in one location, they were more easily able to sell to a different location. They felt the impacts, but not as much as the small scale fisheries that then had to depend on looking for local buyers."

Frozen seafood products, according to the paper, "were generally less affected."

One interesting development has been the uptick in seafood delivery and takeout, which has been picking up some -- but not all -- of the slack in restaurant demand.

"It's unclear to us the level of substitution and what it means in the long term, especially how people are consuming seafood at home," said Froehlich, who is interested in how this consumption pattern might influence the demand for certain species over time.

Because of COVID-19's variable effects across the entire seafood industry, according to the researchers, future federal support should be aimed at locations and sub-sectors "most affected by the pandemic: fishery-dependent communities, processors and fisheries and aquaculture that focus on fresh products."

"A lot of communities are dependent on fisheries," White said. "There are fisheries for tourism, for livelihoods, and a lot of indigenous communities focus on fishing. And it's not just fishing but also fish processing, all the different people that are involved. If you have COVID popping up just when you're about to go fishing and make all the money you're going to have for the year, now you can't make any of that."

The pandemic has highlighted some of the stress points in the U.S.'s seafood supply chain, the researchers said. Preserving a diversity of the sub-sectors within the seafood industry -- for instance, small local operations as well as large fisheries -- will keep the entire system resilient to shocks.

"If you have locally-sourced seafood, if you have aquaculture and fisheries, if you have small-scale and large-scale, this is a little more robust," White said.

This study is the first to be produced from the wealth of data the researchers gathered. A parallel study will publish in the journal Marine Policy that examines how policy, particularly the new federal seafood acts and executive orders, can support more integrated management and diversification of the US seafood sector. The researchers hope the information will help guide the rebuilding of the flagging U.S. seafood industry to a be more resilient to future shocks, including climate change impacts.

"As new mandates and legislation around fisheries and aquaculture are being rolled out during COVID-19 at the national and state levels, we have an opportunity to really think about what the actual targets and goals are. How do we build in more resilience now, instead of retroactively, when the system gets disrupted again," Froehlich said. "Because it will."

In the COVID-19 pandemic, 57 million people have already been infected worldwide. In the search for vaccines and therapies, a precise understanding of the virus, its mutations and transmission mechanisms is crucial. A recent study by the research group of Principal Investigator Andreas Bergthaler at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, in the renowned journal Science Translational Medicine, makes an important contribution to this. The high quality of epidemiological data in Austria, together with state-of-the-art virus genome sequencing, has supported unprecedented insights of the mutation behaviour and transmission of the SARS-CoV-2 virus.

The project "Mutational dynamics of SARS-CoV-2 in Austria" was launched by CeMM in close cooperation with the Medical University of Vienna at the end of March. Together with the Austrian Agency for Health and Food Safety (AGES) and in cooperation with numerous universities and hospitals all over Austria, scientists are working on drawing a more precise picture of the virus mutations and transmissions that occur by genome sequencing of SARS-CoV-2 viruses. Under the leadership of CeMM Principal Investigators Andreas Bergthaler and Christoph Bock, 750 samples from important SARS-CoV-2 infection clusters in Austria such as the tourist town of Ischgl and Vienna were phylogenetically and epidemiologically reconstructed and their role in transcontinental virus spread was analysed. The results also provide important information on transmission and the development of mutations in the SARS-CoV-2 virus.

Mutation analyses revealed correlations between clusters

Based on epidemiological data, the scientists used mutation analyses to reconstruct a SARS-CoV-2 cluster consisting of 76 cases and to uncover a cryptic link between two epidemiological clusters. "This example illustrates how contact tracing and virus mutation analysis together provide a strong pillar of modern pandemic control," says project leader Andreas Bergthaler. Franz Allerberger, Head of the Public Health Division of AGES and co-author of the study, agrees: "The modern techniques of virus genome sequencing support epidemiological contact tracing and offer high-resolution insights of the ongoing pandemic."

Researchers observe the development of new mutations

A special feature of the study is that a chain of eight consecutive transmissions was analysed. "The transmission chain started with a returnee from Italy. Within 24 days, the SARS-CoV-2 virus spread in the greater Vienna region via public and social events in closed rooms", say the CeMM study authors Alexandra Popa and Jakob-Wendelin Genger. The precise breakdown of the transmission chain enabled the scientists to closely observe the development of a new mutation of SARS-CoV-2. "Thanks to excellent epidemiological and our deep virus sequencing data, we could follow how the SARS-CoV-2 virus mutated in one individual and was then transmitted to others," explains Andreas Bergthaler. In addition, the scientists observed the mutation behaviour of the virus during the course of the disease in 31 patients. This may help in the future to assess whether treatments influence the mutation characteristics of the virus.

On average 1,000 virus particles are transmitted during an infection

The results of the current analyses also show that on average 1000 infectious virus particles are transmitted from one infected person to the next. These values are overall considerably higher than for other viruses such as HIV or noroviruses. Andreas Bergthaler adds: "Yet, occasionally we also found infected people who apparently came into contact with fewer virus particles and still became infected. We suspect that parameters such as the application of protective measures, the transmission route or the immune system may play a decisive role here." These results raise important new questions and hypotheses. Reducing the viral load of infected individuals by a combination of measures such as mouth-nose protection, physical distance and adequate indoor air exchange could play a key role in both preventing the spread of the virus and possibly even influence the course of the disease.

The current study based on data collected during the early phase of the SARS-CoV-2 pandemic in spring 2020, provides important insights into the fundamental dynamics of SARS-CoV-2 mutations within patients and during transmission events. These results support other ongoing research projects aiming at a better understanding and controlling the pandemic.

HOUSTON - (Nov. 23, 2020) - Rice University biochemists Michael Stern and James McNew have studied how neurodegeneration kills cells. They've conducted countless experiments over more than a decade, and they've summarized all they've learned in a simple diagram they hope may change how doctors perceive and treat degenerative diseases as varied as Alzheimer's, Parkinson's and muscle atrophy.

In a study published this month in Molecular Psychiatry, McNew and Stern propose that degeneration, at the cellular level, occurs in two distinct phases that are marked by very different activities of protein signaling pathways that regulate basic cell functions.

"We would like clinicians and other researchers to understand that the two phases of degeneration represent distinct entities, with distinct alterations in signaling pathways that have distinct effects on disease pathology," Stern said. "In other words, we think that patients need to be treated differently depending on which phase they are in."

Stern and McNew's diagram shows how the activity of key cell signaling proteins either increases or decreases at the onset of degeneration, ultimately bringing about oxidative stress. Oxidative stress then brings about the second phase of the condition, during which degeneration occurs, where the signaling proteins implicated in the first phase behave in a completely different way.

Because cells behave quite differently in the two phases, the research suggests patients in different phases of a disease may respond differently to the same treatment.

"The two phases of degeneration haven't been previously recognized, so it hasn't been understood, clinically, that you have two different populations of patients," McNew said. "Today, they're treated like one population, and we think this has confounded clinical trials and explains why some trials on Alzheimer's have given variable and irreproducible effects. It would be like trying to treat all meningitis patients with antibiotics without realizing that there are two types of meningitis, one bacterial and one viral."

Stern and McNew, professors of biochemistry and cell biology in Rice's Department of BioSciences, became interested in the cellular processes of neurodegenerative disorders when they began studying hereditary spastic paraplegia (HSP) in the late 2000s. A rare disorder, HSP is marked by numbness and weakness in the legs and feet due to the progressive deterioration of neurons that connect the spine and lower leg.

These are some of the longest cells in the body, and starting with clues about structural defects that could cause them to degenerate, McNew and Stern used experiments on fruit flies to systematically piece together the biochemical domino effect that caused the neurons to progressively lose more and more function and eventually die. It had been thought that nerve damage could lead to muscle atrophy, but their studies found that muscle cells attached to the neurons started degenerating from the same type of biochemical cascade before the nerve cells died.

A key player in the cascade was a protein called TOR, a master regulator of cell growth and an essential protein for all higher order life from yeast to humans. TOR acts like a knob, dialing growth up or down to suit the conditions a cell is experiencing. In some conditions, high growth is warranted and beneficial, and in other situations growth needs to be dialed back so energy and resources can be conserved for daily chores, like the recycling or repair that take place during a process known as autophagy.

Some cancers highjack TOR to promote aggressive cell growth, and increased TOR activity has also been implicated in neurodegenerative disorders like Alzheimer's and Parkinson's diseases and in diseases marked by muscle atrophy. After compiling evidence about how TOR and several other signaling proteins behaved in neurodegeneration, McNew and Stern won a grant from the National Institute of Neurological Disorders and Stroke in 2018 for experiments to investigate signaling pathway changes that occur in the early stages of degeneration.

"At the time, we thought there might be a late phase during which degeneration actually occurs, but we didn't propose any experiments to test that," Stern said. "In the new paper, we're explicit about the existence of a late phase. We propose mechanistically why degeneration occurs only during this phase, and cite abundant research in support."

Stern said the two-phase process described in the study "is the basic engine that drives most or even all forms of degeneration forward. However, in addition, there are also inputs whose role is to specify how fast the engine turns over."

To understand neurodegeneration, it's critical to understand how those inputs work, he said. For example, insulin resistance plays a well-known role in driving Alzheimer's disease, and in the study McNew and Stern describe how it does that by accelerating progression through the early phase.

"Similarly, our data suggests that decreases in synaptic transmission, as occurs in our HSP insect model, likewise triggers degeneration by accelerating progression through the early phase," McNew said. "Our NIH grant was funded so that we could learn the mechanism by which that occurs."

Now that they clearly understand that two phases of degeneration exist, Stern said he and McNew would like to carry out more experiments to see how the effects of specific genes on degeneration are altered when they are activated in the early and late phases.

"What we would like to do in the last two years of the grant is to obtain data to test some of the predictions we have made, which will help determine if the ideas we have presented are likely to be correct," Stern said.

PHILADELPHIA (November 23 2020) - Survivors of COVID-19 are a vulnerable population who often have health ramifications from their illness and hospital stay. Upon returning home from acute care, large proportions of survivors experience functional dependencies, pain, dyspnea, and exhaustion. Until now, no data has been available on the outcomes of COVID-19 patients discharged home after hospitalization and their recovery needs.

In a new study from the University of Pennsylvania School of Nursing (Penn Nursing), rich data from more than 1,400 COVID-19 patients admitted to home health care after hospital discharge describes home visit care and recovery extent. In the study, 94 percent of the patients discharged to home health care, which included skilled nursing and physical therapy, achieved statistically significant improvements in symptom burden and functional outcomes and 87 percent had no adverse events. The study indicates that increasing referrals to home health care has the potential to provide support and achieve improved recovery for these patients.

"Our findings suggest that acute care providers might carefully consider which COVID-19 survivors would benefit from home health care after hospitalization," writes Kathryn H. Bowles, PhD, RN, FAAN, FACMI, Professor of Nursing and van Ameringen Chair in Nursing Excellence at Penn Nursing. "A decision support tool to identify general hospitalized patients for home health care referral may be helpful." Bowles was the lead investigator of the study.

University of California San Diego School of Medicine researchers found evidence that triclosan -- an antimicrobial found in many soaps and other household items -- worsens fatty liver disease in mice fed a high-fat diet.

The study, published November 23, 2020 in Proceedings of the National Academy of Sciences, also details the molecular mechanisms by which triclosan disrupts metabolism and the gut microbiome, while also stripping away liver cells' natural protections.

"Triclosan's increasingly broad use in consumer products presents a risk of liver toxicity for humans," said Robert H. Tukey, PhD, professor in the Department of Pharmacology at UC San Diego School of Medicine. "Our study shows that common factors that we encounter in every-day life -- the ubiquitous presence of triclosan, together with the prevalence of high consumption of dietary fat --constitute a good recipe for the development of fatty liver disease in mice."

Tukey led the study with Mei-Fei Yueh, PhD, a project scientist in his lab, and Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine.

In a 2014 mouse study, the team found triclosan exposure promoted liver tumor formation by interfering with a protein responsible for clearing away foreign chemicals in the body.

In the latest study, the researchers fed a high-fat diet to mice with type 1 diabetes. As previous studies have shown, the high-fat diet led to non-alcoholic fatty liver disease (NAFLD). In humans, NAFLD is an increasingly common condition that can lead to liver cirrhosis and cancer. Diabetes and obesity are risk factors for NAFLD.

Some of the mice were also fed triclosan, resulting in blood concentrations comparable to those found in human studies. Compared to mice only fed a high-fat diet, triclosan accelerated the development of fatty liver and fibrosis.

According to the study, here's what's likely happening: Eating a high-fat diet normally tells cells to produce more fibroblast growth factor 21, which helps protects liver cells from damage. Tukey and team discovered that triclosan messes with two molecules, ATF4 and PPARgamma, which cells need to make the protective growth factor. Not only that, the antimicrobial also disrupted a variety of genes involved in metabolism. In addition, the mice exposed to triclosan had less diversity in their gut microbiomes -- fewer types of bacteria living in the intestines, and a makeup similar to that seen in patients with NAFLD. Less gut microbiome diversity is generally associated with poorer health.

So far, these findings have only been observed in mice who ingested triclosan. But since these same molecular systems also operate in humans, the new information will help researchers better understand risk factors for NAFLD, and give them a new place to start in designing potential interventions to prevent and mitigate the condition.

"This underlying mechanism now gives us a basis on which to develop potential therapies for toxicant-associated NAFLD," said Tukey, who is also director of the National Institute of Environmental Health Sciences Superfund Program at UC San Diego.

In 2016, the U.S. Food and Drug Administration (FDA) ruled that over-the-counter wash products can no longer contain triclosan, given that it has not been proven to be safe or more effective than washing with plain soap and water. However, the antimicrobial is still found in some household and medical-grade products, as well as aquatic ecosystems, including sources of drinking water.

An estimated 100 million adults and children in the U.S. may have NAFLD. The precise cause of NAFLD is unknown, but diet and genetics play substantial roles. Up to 50 percent of people with obesity are believed to have NAFLD. The condition typically isn't detected until it's well advanced. There are no FDA-approved treatments for NAFLD, though several medications are being developed. Eating a healthy diet, exercising and losing weight can help patients with NAFLD improve.

VIRTUAL MEETING (CST), November 22, 2020 -- Researchers who study the physics of fluids are learning why certain situations increase the risk that droplets will transmit diseases like COVID-19.

At the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics, the scientists offered new evidence showing why it's dangerous to meet indoors--especially if it's cold and humid, and even if you're more than six feet away from other people. They suggested which masks will catch the most infectious droplets. And they provided new tools for measuring super-spreaders.

"Present epidemiological models for infectious respiratory diseases do not account for the underlying flow physics of disease transmission," said University of Toronto engineering professor Swetaprovo Chaudhuri, one of the researchers.

But fluids and their dynamics are critical for shaping pathogen transport, which affects infectious disease transmission, explained mathematical physicist and professor Lydia Bourouiba, Director of The Fluid Dynamics of Disease Transmission Laboratory at MIT. She gave an invited talk on the body of work she has produced over the last ten years elucidating the fluid dynamics of infectious diseases and disease transmission.

"My work has shown that exhalations are not isolated droplets but in fact come out as a turbulent, multiphase cloud. This gas cloud is critical in enhancing the range and changing the evaporation physics of the droplets within it," said Bourouiba. "In the context of respiratory infectious diseases, particularly now COVID-19, this work underscores the importance of changing distancing and protection guidelines based on fluid dynamics research, particularly regarding the presence of this cloud."

Bourouiba presented examples from a range of infectious diseases including COVID-19 and discussed the discovery that exhalation involves different flow regimes, in addition to rich unsteady fluid fragmentation of complex mucosalivary fluid. Her research reveals the importance of the gas phase, which can completely change the physical picture of exhalation and droplets.

Nordic Institute for Theoretical Physics scientist Dhrubaditya Mitra and his team realized they could use the mathematical equations that govern perfume to calculate how long it would take for viral droplets to reach you indoors. It turns out: not very long at all.

Perfume worn by someone at the next table or cubicle reaches your nose thanks to turbulence in the air. Fine droplets spewed by an infected person spread in the same way. The researchers found that below a relative distance known as the integral scale, droplets move ballistically and very fast.

Even above the integral scale, there is danger. Consider an example where the integral scale is two meters. If you were standing three meters--just under ten feet--from an infected person, their droplets would almost certainly reach you in about a minute.

"It showed us how futile most social distancing rules are once we are indoors," said Mitra, who conducted the research with colleague Akshay Bhatnagar at the Nordic Institute for Theoretical Physics and Akhilesh Kumar Verma and Rahul Pandit at the Indian Institute of Science.

Besides traveling further and faster, droplets may also survive longer indoors than previously believed.

Research in the 1930s analyzed how long respiratory droplets survive before evaporating or hitting the ground. The nearly century-old findings form the basis of our current mantra to "stay six feet away" from others.

Physicists from the University of Twente revisited the issue. They conducted a numerical simulation indicating that droplet lifetimes can extend more than 100 times longer than 1930s standards would suggest.

"Current social distancing rules are based on a model which by now should be outdated," said physicist Detlef Lohse, who led the team.

In a cold and humid space, exhaled droplets don't evaporate as quickly. The hot moist puff produced also protects droplets and extends their lifetimes, as do collective effects.

Some droplets are more likely than others to make you sick. University of Toronto's Chaudhuri, with researchers from the Indian Institute of Science and the University of California San Diego, investigated why, using human saliva droplet experiments and computational analyses.

They found that some of the most infectious droplets start out at 10 to 50 microns in size. "With certain assumptions, it appears that if everyone wears a mask that can prevent ejection of all droplets above 5 microns, the pandemic curve could be flattened," said Chaudhuri.

Dried droplet residue also poses a serious risk: It persists much longer than droplets themselves and can infect large numbers of people if the virus remains potent.

The team used their findings to develop a disease transmission model. "Our work connects the microscale droplet physics and its fundamental role in determining the infection spread at a macroscale," said Chaudhuri.

To better understand droplet dynamics in the COVID-19 pandemic, a team from Northwestern University and the University of Illinois at Urbana-Champaign tested the capacities of a new wearable device. The thin, wireless, flexible sensor attaches like a sticker to the bottom of the neck to capture vital signals. Ongoing clinical studies are using the device with hospital patients.

The team found that the device distinguishes between coughing, talking, laughing, and other breathing activities with its machine learning algorithms. Researchers used particle tracking velocimetry and a decibel meter to analyze droplets produced by device wearers.

"Different types of speech can generate drastically different numbers and dynamics of droplets," said biomedical engineering researcher Jin-Tae Kim, who led the investigation.

The device can help shed light on why some individuals become unusually infectious--the so-called super-spreaders. "Our findings further address the critical need for continuous skin-integrated sensors to better comprehend the pandemic," said Kim.

President-elect Joe Biden has signaled that fighting the COVID-19 pandemic will be an immediate priority for his administration. He recently announced a coronavirus advisory board of infectious disease researchers and former public health advisers along with an updated strategy that will include increases in testing and contact tracing, as well as transparent communication.

But Inauguration Day is still two months away. The number of confirmed COVID-19 cases are likely to increase to 20 million by the end of January, nearly doubling the current level of 11.4 million cases, predicts a Washington University in St. Louis COVID-19 forecasting model.

The model, which accurately forecasted the rate of COVID-19 growth over the summer of 2020, was developed by Olin Business School's Meng Liu, Raphael Thomadsen and Song Yao. Their paper presenting the model and its forecasts was published Nov. 23 by Scientific Reports.

"One of the key reasons for the increased accuracy of this model over other COVID-19 forecasts is that this model accounts for the fact that people live in interconnected social networks rather than interacting mostly with random groups of strangers," said Thomadsen, professor of marketing. "This allows the model to forecast that growth will not continue at exponential rates for long periods of time, as classic COVID-19 forecasts predict."

An interactive online version of the model also allows users to observe the impact different levels of social distancing will have on the spread of COVID-19. The current social distancing reflects an approximate 60% return to normalcy, as compared with the level of social distancing before the pandemic. If we continue, as a nation, at the current level of social distancing, the model forecasts that we are likely to reach 20 million cases before the end of January 2021.

"Even small increases in social distancing can have a large effect on the number of cases we observe in the next two and a half months," Thomadsen said. "Going back to a 50% return to normalcy, which was the average level of distancing in early August, would likely result in 5 million fewer cases by the end of January.

"We could effectively squash out the COVID growth within a few weeks if we went back to the levels of social distancing we experienced in April."

However, the researchers caution that this is likely a conservative estimate due to increased testing and the upcoming holidays.

"In our model, we assume that only 10% of cases are ever diagnosed, meaning that we will start to hit saturation," said Song Yao, associate professor of marketing and study co-author. "However, more recently, testing has increased, and probably more like 25% of cases are diagnosed. In that case, total COVID cases would increase beyond 20 million in the next few months unless we, as a society, engage in more social distancing."

"The upcoming holiday seasons will present a great deal of uncertainty to the outlook of the pandemic as people travel more at the end of the year. This will likely make our forecast an optimistic one," said Meng Liu, assistant professor of marketing and study co-author.

New research from the Prevention Research Center of the Pacific Institute for Research and Evaluation suggests that adverse childhood experiences, often referred to as child maltreatment, are associated with increased odds of substance use among women urban Emergency Department (ED) patients.

To study the question, the research scientists used a cross-sectional survey with 1,037 married or partnered ED patients at a public safety-net hospital that gathered information about at-risk drinking, cannabis, and illicit drug use. As a safety-net hospital, most of the patients seeking medical care are of low socio-economic status, and most are African American or Hispanic.

Adverse childhood experiences were measured as:

exposure to a mentally ill person in the home

parent/caregiver alcoholism

sexual abuse

physical abuse

psychological abuse

violence directed against the respondent's mother

The results showed that at least one adverse childhood experience was reported by 53% of men and 60% of women. Moreover:

Women whose mothers were victims of domestic violence had greater chances of at-risk drinking,

Women with multiple adverse experiences were more likely to use cannabis,

Women with multiple adverse experiences were more likely use illicit drugs.

Men's individual or multiple adverse childhood experiences were not associated with increased likelihood for any of the outcomes.

Says lead author, Dr. Carol Cunradi: "Health disparities are pervasive among underserved populations, such as those seeking care at urban EDs. So it is important to understand how adverse childhood experiences are linked with substance use among urban ER patients. The prevalence of exposure to childhood maltreatment in this urban ED sample underscores the importance of ED staff providing trauma-informed care to patients, including the delivery of brief interventions and referral to treatment."

Washington, DC - November 20, 2020 - The measles-mumps-rubella (MMR) vaccine has been theorized to provide protection against COVID-19. In a new study published in mBio, an open-access journal of the American Society for Microbiology, researchers provide further proof of this by showing that mumps IgG titers, or levels of IgG antibody, are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with the MMR II vaccine produced by Merck. MMR II contains the Edmonston strain of measles, the Jeryl Lynn (B-level) strain of mumps, and the Wistar RA 27/3 strain of rubella.

"We found a statistically significant inverse correlation between mumps titer levels and COVID-19 severity in people under age 42 who have had MMR II vaccinations," said lead study author Jeffrey E. Gold, president of World Organization, in Watkinsville, Georgia. "This adds to other associations demonstrating that the MMR vaccine may be protective against COVID-19. It also may explain why children have a much lower COVID-19 case rate than adults, as well as a much lower death rate. The majority of children get their first MMR vaccination around 12 to 15 months of age and a second one from 4 to 6 years of age."

In the new study, the researchers divided 80 subjects into 2 groups. The MMR II group consisted of 50 U.S. born subjects who would primarily have MMR antibodies from the MMR II vaccine. A comparison group of 30 subjects had no record of MMR II vaccinations, and would primarily have MMR antibodies from other sources, including prior measles, mumps, and/or rubella illnesses. The researchers found a significant inverse correlation (rs = -0.71, P

Within the MMR II group, mumps titers of 134 to 300 AU/ml (n=8) were only found in those who were functionally immune or asymptomatic. All with mild COVID-19 symptoms had mumps titers below 134 AU/ml (n=17). All with moderate symptoms had mumps titers below 75 AU/ml (n=11). All who had been hospitalized and required oxygen had mumps titers below 32 AU/ml (n=5). Titers were measured by Quest Diagnostics using their standard diagnostic protocol.

"This is the first immunological study to evaluate the relationship between the MMR II vaccine and COVID-19. The statistically significant inverse correlation between mumps titers and COVID-19 indicates that there is a relationship involved that warrants further investigation," said coauthor David J. Hurley, PhD, professor and molecular microbiologist at the University of Georgia. "The MMR II vaccine is considered a safe vaccine with very few side effects. If it has the ultimate benefit of preventing infection from COVID-19, preventing the spread of COVID-19, reducing the severity of it, or a combination of any or all of those, it is a very high reward low risk ratio intervention. Maximum seropositivity is achieved through two vaccinations at least 28 days apart. Based upon our study, it would be prudent to vaccinate those over 40 regardless of whether or not they already have high serum MMR titers."