Oregon: CDC investigating woman's death after J&J vaccine

PORTLAND, Ore. — Oregon health officials said Thursday that federal officials are investigating the death of a woman in her 50s who developed a rare blood clot and low platelets within two weeks of receiving the Johnson & Johnson vaccine against COVID-19.

The Oregon Health Authority learned of the probe on Tuesday, two days after the U.S. Centers for Disease Control and Prevention began the investigation, the agency said. The woman, whose name was not released, received the dose before the CDC ordered a pause on the vaccine amid concerns it could cause dangerous clots.

The woman developed a “rare but serious blood clot in combination with very low platelets,” OHA said in a statement.

Dr. Shimi Sharief, senior health advisor for the state’s health authority, said the woman’s symptoms were consistent with other cases — severe headache, abdominal pain, leg pain or shortness of breath .

Health officials declined to release any further details, including the date the woman got the vaccine or where in Oregon she lived, citing patient privacy. The woman was hospitalized before her death and got the vaccine in early April, Sharief said.

Until the investigation is complete, which health officials predict will take a week or more, it’s not certain that her death is related to the vaccine, the agency said.

Federal and state agencies paused the J&J vaccine rollout on April 13 due to concerns about blood clots.

“For most people that received the (J&J) vaccine, we are nearing the end of that time of where they need to be monitoring for symptoms,” Sharief said. The CDC warned that if people have symptoms within three weeks after receiving the vaccine they should contact their health care provider.

Federal officials already were examining six reports of the unusual clots, including a death, out of more 8 million Americans given the one-dose vaccination so far.

The CDC also told Texas health authorities Thursday that a woman in that state was hospitalized with possible blood clots associated with J&J vaccine recipients.

A government advisory committee on vaccines is expected to meet Friday and could make a recommendation soon after on whether and how to resume use of the J&J vaccine.

Sharief said whether Oregon resumes distribution of the J&J vaccine will be a “reflection” of the committee’s decision.

“We have the utmost confidence that it would be a decision made with thorough investigation and consideration of the potential benefits and risks, in relation to each other, as we go through this pandemic,” Sharief said.

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Cline is a corps member for The Associated Press/Report for America Statehouse News Initiative. Report for America is a nonprofit national service program that places journalists in local newsrooms to report on undercovered issues.

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Mediterranean diet with lean beef may lower risk factors for heart disease

lean beef

Eating red meat may have a bad reputation for being bad for the heart, but new research found that lean beef may have a place in healthy diets, after all.

In a randomized controlled study, researchers found that a Mediterranean diet combined with small portions of lean beef helped lower risk factors for developing heart disease, such as LDL cholesterol.

Jennifer Fleming, assistant teaching professor of nutrition at Penn State, said the study suggests that healthy diets can include a wide variety of foods, such as red meat, and still be heart friendly.

“When you create a healthy diet built on fruits, vegetables, and other plant-based foods, it leaves room for moderate amounts of other foods like lean beef,” Fleming said. “There are still important nutrients in beef that you can benefit from by eating lean cuts like the loin or round, or 93% lean ground beef.”

David J. Baer, research leader at the United States Department of Agriculture—Agricultural Research Service, and study co-principal investigator, added, “This study highlights the importance of including lean beef in a Mediterranean dietary pattern that can yield heart-healthy benefits.”

According to the researchers, red meat such as beef has been associated with an increased risk for cardiovascular disease in previous studies. But it has remained unclear whether red meat actually causes these effects or if they actually are caused by other diet and lifestyle choices that people engage in alongside red meat consumption.

Additionally, the researchers said many studies have combined both fresh and processed meats together when evaluating red meat consumption and health. Processed red meats have a very different nutrient profile than fresh meat—for example, processed meat products are much higher in sodium—that could explain the red meat research that has been reported.

“The Mediterranean diet is traditionally low in red meat,” Fleming said. “But, knowing that many Americans enjoy red meat, we wanted to examine how combining lean beef with the Mediterranean diet would affect cardiovascular risk markers.”

The study included 59 participants. Every participant consumed each diet for four weeks each, with a one week break between each diet period, and blood samples were drawn at the beginning of the study as well as after each diet period.

Three of the four diet periods contained different amounts of beef to a Mediterranean diet plan, which provided 41% calories from fat, 42% from carbohydrates and 17% from protein. In addition to the control average American diet, one diet provided 0.5 ounces of beef a day, which is the amount recommended in the Mediterranean diet pyramid. A second diet provided 2.5 ounces a day, which represents the amount an average American eats in a day, and the third experimental diet included 5.5 ounces a day, which previous research connected with certain heart health benefits.

All three Mediterranean diet periods included olive oil as the predominant fat source, three to six servings of fruits, and six or more servings of vegetables a day. The beef included in these diet periods was either lean or extra-lean.

Fleming said they were able to use a special technology called nuclear magnetic resonance—or NMR technology—to measure the number and size of lipoprotein particles. She said this study was one of the first randomized controlled trials of the Mediterranean diet to use the technique.

“This is important because there is growing evidence to suggest that LDL particle number is more strongly associated with cardiovascular disease risk than total blood LDL concentrations alone,” Fleming said. “Moreover, we were able to identify changes in apolipoproteins, specifically apoB, which are also associated with increased CVD risk.”

After the data were analyzed, the researchers found that participants all had lower LDL cholesterol following the Mediterranean diet periods compared to the average American diet. But while the total numbers of LDL particles were reduced following all three Mediterranean diet periods, they were only significantly decreased when following those periods that included 0.5 or 2.5 ounces of beef a day compared to the average American diet.

Additionally, non-HDL cholesterol and apoB—a protein involved in lipid metabolism and a marker of CVD risk—were lower following all three Mediterranean diet periods compared to the average American diet.

Fleming said the study—recently published in the American Journal of Clinical Nutrition—underscores the importance of consuming healthy, well-balanced diets.

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To combat gum disease, help oral bacteria evolve

To combat gum disease, help oral bacteria evolve

Liver disease, from metabolic and bacterial causes, is a growing concern. What connects these dots? The gut, or more specifically, bacteria in the gut. Bacteria that cause inflammation in the mouth are transported through the digestive tract to the gut and liver, where they can cause liver inflammation. Lipopolysaccharides, important structural molecules in some bacteria, act as endotoxins, producing systemic effects that can manifest as non-alcoholic fatty liver disease (NAFLD). Now, a multidisciplinary team from the University of Tsukuba show that exercise could be used to improve the oral environment in people with NAFLD, potentially leading to a new treatment for the disease.

These researchers previously demonstrated that exercise benefits patients with NAFLD by reducing fat, inflammation, and scarring in the liver; improving the liver’s response to and clearance of the endotoxin; and reducing gum disease. With the latest study in their series, they add another signpost to uncharted territory:

“We know that exercise has innumerable benefits to health overall and for these specific conditions,” says corresponding author Professor Junichi Shoda. “With this study, we sought to characterize underlying mechanisms—that is, show how exercise alters physiology and how altered physiology induces changes in oral bacteria.”

The researchers carried out biochemical and genetic analyses on saliva from overweight men with NAFLD and gum disease before and after 12-week exercise or diet programs. Men in both groups were able to lose fat mass, but those following dietary restrictions also lost muscle mass, whereas those following the exercise program gained muscle mass. “More importantly, we found that reductions in lactoferrin, lipopolysaccharide, and IgA concentrations were only evident in the men who followed the exercise regimen,” Professor Shoda explains, “which suggested that the oral environment had been significantly altered by exercise.”

The samples from the exercise group also showed increased bacterial diversity and changes in the relative constituent bacterial populations. In the overall population, more bacteria expressed genes related to environmental information processing, and less bacteria expressed genes related to genetic information processing and metabolism. In fact, bacteria expressed fewer genes for producing lipopolysaccharides.

“Therefore, it seems that, in people with both non-alcoholic liver disease and gum disease, exercise causes a biochemical shift in the environment of the mouth that favors the survival of less harmful bacteria,” explains Professor Shoda.

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Aluminum is intricately associated with the neuropathology of familial Alzheimer’s disease

Aluminum is intricately associated with the neuropathology of familial Alzheimer's disease

A new study builds upon two earlier published studies (Mold et al., 2020, Journal of Alzheimer’s Disease Reports) from the same group. The new data, also published in the Journal of Alzheimer’s Disease Reports, demonstrate that aluminum is co-located with phosphorylated tau protein, present as tangles within neurons in the brains of early-onset or familial Alzheimer’s disease (AD). “The presence of these tangles is associated with neuronal cell death, and observations of aluminum in these tangles may highlight a role for aluminum in their formation,” explained lead investigator Matthew John Mold, Ph.D., Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.

The earlier research highlighted widespread co-localization of aluminum and amyloid-β in brain tissue in familial AD. The researchers used a highly-selective method of immunolabelling in the current study, combined with aluminum-specific fluorescence microscopy. Phosphorylated tau in tangles co-located with aluminum in the brain tissue of the same cohort of Colombian donors with familial AD were identified. “It is of interest and perhaps significance with respect to aluminum’s role in AD that its unequivocal association with tau is not as easily recognizable as with amyloid-β. There are many more aggregates of aluminum with amyloid-β than with tau in these tissues and the latter are predominantly intracellular,” remarked co-author, Professor Christopher Exley.

Per Dr. George Perry, Editor-in-Chief of Journal of Alzheimer’s Disease, “Aluminum accumulation has been associated with Alzheimer’s disease for nearly half a century, but it is the meticulously specific studies of Drs. Mold and Exley that are defining the exact molecular interaction of aluminum and other multivalent metals that may be critical to formation of the pathology of Alzheimer’s disease.”

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Distinct Parkinson’s disease symptoms tied to different brain pathways

Distinct Parkinson's disease symptoms tied to different brain pathways

Parkinson’s disease (PD) is well known as a debilitating disease that gradually worsens over time. Although the disease’s progression has been largely tied to the loss of motor functions, non-motor symptoms, including the loss of cognitive abilities, often emerge early in the disease.

Much less understood is the role that specific neural circuits play in these distinct motor and non-motor functions.

A new study led by neurobiologists at the University of California San Diego and their colleagues found that specific, identifiable neural pathways are charged with particular functions during stages of the disease. Their findings, published recently in Nature Neuroscience, can help form the basis for improving therapeutic strategies for precise symptoms of Parkinson’s at various levels of disease progression.

The researchers used a mix of approaches to shed more light on the anatomical and functional importance of a center of brain circuitry known as the basal ganglia, located deep in the cranium. Specifically, the researchers, working in mice, investigated circuit pathways tied to specific neurons in the external globus pallidus, or GPe, and their role in different Parkinson’s disease-related behaviors. The GPe is known for its strong output and influence on several downstream brain regions.

The investigations included a multi-pronged approach using electrophysiology, viral tracing and behavioral experiments. The researchers identified two populations of GPe neurons and their distinctive pathways tied to different behavioral symptoms.

“Our work demonstrates that the distinct neural circuitries in the basal ganglia are differentially involved in the motor and non-motor symptoms of Parkinsonian-like behaviors that occur at different stages of the disease,” said Lim, an associate professor in the Neurobiology Section of the Division of Biological Sciences at UC San Diego. “This suggests that evaluation of the detailed circuit mechanisms is needed to fully understand the changes in brain during the progression of PD, and could provide better therapeutic strategies for the treatment of PD.”

Lim said the most surprising finding from the research was the fact that dopaminergic neurons, those that are gradually lost during Parkinson’s disease progression, could be linked so specifically to changes in different brain areas.

“Selective manipulation of specific changes can rescue one type of symptom—without affecting other symptoms—of Parkinson’s Disease,” said Lim.

With the new framework in hand, Lim and his colleagues are now looking deeper at the circuit pathways and how they are tied to different disease symptom stages, in particular with an emphasis on delaying the progression of the disease.

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Study ratifies link of processed meat to cardiovascular disease and death

processed meat

A global study led by Hamilton scientists has found a link between eating processed meat and a higher risk of cardiovascular disease. The same study did not find the same link with unprocessed red meat or poultry.

The information comes from the diets and health outcomes of 134,297 people from 21 countries spanning five continents, who were tracked by researchers for data on meat consumption and cardiovascular illnesses.

After following the participants for almost a decade, the researchers found consumption of 150 grams or more of processed meat a week was associated with a 46 percent higher risk of cardiovascular disease and a 51 percent higher risk of death than those who ate no processed meat.

However, the researchers also found moderate levels of consumption of non-processed meats had a neutral effect on health.

“Evidence of an association between meat intake and cardiovascular disease is inconsistent. We therefore wanted to better understand the associations between intakes of unprocessed red meat, poultry, and processed meat with major cardiovascular disease events and mortality,” said Romaina Iqbal, first author of the study and an associate professor at the Aga Khan University in Karachi, Pakistan.

“The totality of the available data indicates that consuming a modest amount of unprocessed meat as part of a healthy dietary pattern is unlikely to be harmful,” said Mahshid Dehghan, investigator for the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

The Prospective Urban Rural Epidemiology (PURE) study was launched in 2003 and is the first multinational study that provides information on the association between unprocessed and processed meat intakes with health outcomes from low, middle and high-income countries.

“The PURE study examines substantially more diverse populations and broad patterns of diet, enabling us to provide new evidence that distinguishes between the effects of processed and unprocessed meats,” said senior author Salim Yusuf, executive director of the PHRI.

Participants’ dietary habits were recorded using food frequency questionnaires, while data was also collected on their mortality and major cardiovascular disease events. This allowed researchers to determine the associations between meat consumption patterns and cardiovascular disease events and mortality.

The authors believe that additional research may improve current understanding of the relationship between meat consumption and health outcomes. For example, it is unclear what study participants with lower meat intakes were eating instead of meat, and if the quality of those foods differed between countries.

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Gene therapy using ‘zinc fingers’ may help treat Alzheimer’s disease, animal study shows

brain

Researchers have used a genetic engineering strategy to dramatically reduce levels of tau—a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer’s disease—in an animal model of the condition. The results, which come from investigators at Massachusetts General Hospital (MGH) and Sangamo Therapeutics Inc., could lead to a potentially promising treatment for patients with this devastating illness.

As described in Science Advances, the strategy involves a gene regulation technology called zinc finger protein transcription factors (ZFP-TFs), which are DNA-binding proteins that can be harnessed to target and affect the expression of specified genes. In this case, the therapy was designed to target and silence the expression of the gene that codes for tau. Mice with Alzheimer’s disease received a single injection of the treatment—which employed a harmless virus to deliver the ZFP-TFs to cells—directly into the hippocampus region of the brain or intravenously into a blood vessel. Treatment with ZFP-TFs reduced tau protein levels in the brain by 50% to 80% out to 11 months, the longest time point studied. Importantly, the therapy reversed some of the Alzheimer’s-related damage that was present in the animals’ brain cells.

“The technology worked just the way we had hoped—reducing tau substantially for as long as we looked, causing no side effects that we could see even over many, many months, and improving the pathological changes in the brains of the animals,” says senior author Bradley Hyman, MD, Ph.D., who directs the Alzheimer’s disease research unit at the MassGeneral Institute for Neurodegenerative Disease. “This suggests a plan forward to try to help patients.”

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Using the power of artificial intelligence to detect disease

AI

A large international collaboration, led by A/Prof Xiu Ying Wang and Prof Manuel Graeber of the University of Sydney, has developed an innovative, advanced artificial intelligence (AI) application, PathoFusion, that could be used for the examination of routine tissue samples in order to identify indications of cancer.

The research melds contributions from computer scientists, neuropathologists, neuosurgeons, medical oncologists and medical imaging scientists.

ANSTO’s Prof Richard Banati, a Professor of Medical Radiation Sciences/Medical Imaging, who studies the brain’s innate immune system using advanced medical imaging techniques, is a co-author on the paper published in the journal, Cancers.

“The idea behind PathoFusion was to create a novel advanced deep learning model to recognize malignant features and immune response markers, independent of human intervention, and map them simultaneously in a digital image,” explained Banati.

Scientists specifically designed a bifocal deep learning framework which is analogous to how a microscopist works in histopathology image analysis. The framework uses a convolutional neural network (ConvNet/CNN), which was originally developed for natural image classification.

This deep learning algorithm can take in an input image, assign importance to various aspects/objects in the image and differentiate one from another.

The experiment to evaluate the model involved the examination of tissue from cases of glioblastoma, an aggressive cancer that affects the brain or spine.

The team used the expert input of neuropathologists to ‘train’ the software to mark key features.

Experiments confirmed that the application achieved a high level of accuracy in recognising and mapping six typical neuropathological features that are markers of a malignancy.

Pathofusion reliably identified forms and structural features with a precision of 94% and sensitivity of 94.7%. and an immune markers at a precision of 96.2% and sensitivity of 96.1%.

The application combines layers of information about dead or dying tissue, the proliferation of microscopic blood vessels and other vasculature with the expression of a tumor genetic marker, CD276, in an image that combines the data in a heatmap.

The image uses strong colors to depict the features and their distribution. Conventional staining techniques are often monochromatic.

“The research confirmed that it is possible to train neural networks effectively using only a relatively small number of cases, that should be useful for some scenarios,” said Banati.

The research was successful in efficiently training a convolutional neural network to recognize key features in stained slides, improving the model and increasing the effectiveness of feature recognition (with fewer physical cases than conventionally needed for neural network training) and establishing a method to include immunological data.

Painstaking and time-consuming routine morphological diagnostic work is carried out by pathologists, who examine individual slides under a microscope to mark and quantify features that are markers of disease and provide the information to clinicians.

“Anticipating further hardware improvements in computing, it should exceed the speed of human microscopic feature recognition by orders of magnitude when whole histological slides are used at high resolution,” said Prof Manuel Graeber of the University of Sydney and Brain and Mind Centre.

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Aspirin use for cardiovascular disease may reduce likelihood of COVID-19 infection

aspirin

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.

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Accelerating gains in abdominal fat during menopause tied to heart disease risk

heart

Women who experience an accelerated accumulation of abdominal fat during menopause are at greater risk of heart disease, even if their weight stays steady, according to a University of Pittsburgh Graduate School of Public Health-led analysis published today in the journal Menopause.

The study—based on a quarter century of data collected on hundreds of women—suggests that measuring waist circumference during preventive health care appointments for midlife women could be an early indicator of heart disease risk beyond the widely used body mass index (BMI)—which is a calculation of weight vs. height.

“We need to shift gears on how we think about heart disease risk in women, particularly as they approach and go through menopause,” said senior author Samar El Khoudary, Ph.D., M.P.H., associate professor of epidemiology at Pitt Public Health. “Our research is increasingly showing that it isn’t so important how much fat a woman is carrying, which doctors typically measure using weight and BMI, as it is where she is carrying that fat.”

El Khoudary and her colleagues looked at data on 362 women from Pittsburgh and Chicago who participated in the Study of Women’s Health Across the Nation (SWAN) Heart study. The women, who were an average age of 51, had their visceral adipose tissue—fat surrounding the abdominal organs—measured by CT scan and the thickness of the internal carotid artery lining in their neck measured by ultrasound, at a few points during the study. Carotid artery thickness is an early indicator of heart disease.

The team found that for every 20% increase in abdominal fat, the thickness of the carotid artery lining grew by 2% independent of overall weight, BMI and other traditional risk factors for heart disease.

They also found that abdominal fat started a steep acceleration, on average, within two years before the participants’ last period and continued a more gradual growth after the menopausal transition.

Saad Samargandy, Ph.D., M.P.H., who was a doctoral student at Pitt Public Health at the time of the research, explained that fat that hugs the abdominal organs is related to greater secretion of toxic molecules that can be harmful to cardiovascular health.

“Almost 70% of post-menopausal women have central obesity—or excessive weight in their mid-section,” said Samargandy, also the first author of the journal article. “Our analysis showed an accelerated increase of visceral abdominal fat during the menopausal transition of 8% per year, independent of chronological aging.”

Measuring abdominal fat by CT scan is expensive, inconvenient and could unnecessarily expose women to radiation—so El Khoudary suggests that regularly measuring and tracking waist circumference would be a good proxy to monitor for accelerating increases in abdominal fat. Measuring weight and BMI alone could miss abdominal fat growth because two women of the same age may have the same BMI but different distribution of fat in their body, she added.

“Historically, there’s been a disproportionate emphasis on BMI and cardiovascular disease,” said El Khoudary. “Through this long-running study, we’ve found a clear link between growth in abdominal fat and risk of cardiovascular disease that can be tracked with a measuring tape but could be missed by calculating BMI. If you can identify women at risk, you can help them modify their lifestyle and diet early to hopefully lower that risk.”

Late last year, El Khoudary led a team in publishing a new scientific statement for the American Heart Association that calls for increased awareness of the cardiovascular and metabolic changes unique to the menopausal transition and the importance of counseling women on early interventions to reduce cardiovascular disease risk factors.

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