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Scientists at the University of Birmingham, UK, have shown that a novel low molecular weight dextran-sulphate, ILB® could play a key role in treating open angle glaucoma (OAG), a neurodegenerative disease that affects over 70 million people worldwide and causes irreversible blindness.

OAG develops slowly over many years. Excessive matrix deposition (fibrosis) within the eye's main fluid drainage site can lead to increased intraocular pressure (IOP), resulting in damage to the optic nerve.1

The research, reported in npj Regenerative Medicine, has shown that that ILB can normalise matrix deposition inside the eye and lower IOP in a pre-clinical model used to mimic these aspects of human glaucoma, paving the way for new anti-fibrotic therapies to be developed for the disease.

OAG is a complex disease and it has proved difficult to develop effective therapeutics to target the biochemical pathways involved. Existing therapies mainly work by reducing fluid production in the eye, not the underlying causes, and even the newer therapies have shown limited success in the clinic.2

The Birmingham scientists focussed on an inflammatory pathway that is common to several diseases, and involves Transforming Growth Factor β (TGFβ), a signalling molecule that communicates between cells and orchestrates both inflammation and fibrosis. TGFβ's role in OAG is well known, with patients demonstrating higher levels in their aqueous humour and laboratory studies showing that artificially increasing TGFβ within the eye can lead to fibrosis3,4.

The scientists found that ILB has multimodal actions across many genes that resolve inflammatory and fibrotic cellular processes. When they progressed their work into a pre-clinical experimental model of glaucoma, they found that daily subcutaneous injections of ILB significantly (p

Clinicians working in ophthalmology generally prefer local over systemically delivered therapeutics, as it is a safer route of administration that is more acceptable to patients.

Dr Hill is leading a project to formulate a topical alternative that will avoid the need for injection. She is working closely on this with Mr Imran Masood, a consultant ophthalmic surgeon at Sandwell and West Birmingham NHS Trust and Professor Liam Grover, a biomaterials expert from the University's Healthcare Technologies Institute, to assess the use of a novel shear thinning fluid gel for the resolution of glaucoma.

The shear thinning fluid gel was developed for use as eye drops that are retained for an extended period of time following administration, and patents have been filed for its use both alone, and in combination with other therapeutics.5 Previous studies have shown the fluid gel reduces corneal scarring when applied topically, and it is an effective carrier molecule for other therapeutics.6

Stomach cancer, or gastric cancer, is a common gastrointestinal malignancy. Peritoneal metastasis occurs in a majority of patients with advanced stomach cancer and is considered as an aggressive disease with poor outcomes.

Patients with peritoneal metastasis are typically not eligible for curative surgery. Therefore, preoperative detection and diagnosis of peritoneal metastasis are critical to inform treatment decision-making and avoid unnecessary surgery.

A new study published in the JAMA Network Open on Jan. 5 shows that deep learning can help predicting the occult peritoneal metastasis in stomach cancer. It provides a novel and noninvasive approach for stomach cancer patients and may inform individualized surgical management of stomach cancer.

The study was conducted by Dr. XIE Yaoqin's group from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, Dr. LI Ruijiang from Stanford University, Dr. LI Guoxin from Nanfang Hospital, and Dr. ZHOU Zhiwei from Sun Yat-sen University Cancer Center.

The researchers developed a deep learning model called Peritoneal Metastasis Network (PMetNet) to predict clinically occult peritoneal metastasis using preoperative computed tomography (CT) images in patients with stomach cancer.

Dr. JIANG Yuming from Stanford University, one co-first author of this study, explained that the proposed deep learning model may serve as a reliable noninvasive tool for the early identification of patients with clinically occult peritoneal metastasis.

"It can also inform individualized preoperative treatment decision-making and may avoid unnecessary surgery and complications," said Ph.D. candidate LIANG Xiaokun from SIAT, the other co-first author.

What The Study Did: Changes in out-of-hospital cardiac arrests and fatalities in the Detroit area during the COVID-19 pandemic are compared with year-earlier events for the same period in this observational study.

Authors: Adrienne V. Nickles, M.P.H., of the Michigan Department of Health and Human Services in Lansing, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.32331)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Sophia Antipolis, 7 January 2021: Patients with acute heart failure nearly double their risk of dying if they get COVID-19, according to research published today in ESC Heart Failure, a journal of the European Society of Cardiology (ESC).1 The small, single centre study highlights the need for patients with heart failure to take extra precautions to avoid catching COVID-19.

"Our results support prioritising heart failure patients for COVID-19 vaccination once it is available," said study lead investigator Dr. Amardeep Dastidar, a consultant interventional cardiologist at North Bristol NHS Trust and Bristol Heart Institute, UK. "In the meantime, heart failure patients of all ages should be considered a high-risk group and be advised to maintain social distance and wear a face mask to prevent infection."

Heart failure refers to progressive weakening of the heart's pump function with symptoms of breathlessness, ankle swelling and fatigue. Sudden and severe worsening of symptoms is called acute heart failure - this is a medical emergency and requires admission to hospital for intravenous medication and intensive monitoring.

This study examined referral rates for acute heart failure during the pandemic and 30-day mortality. The analysis included 283 patients with acute heart failure admitted to the cardiology department of North Bristol NHS Trust. Two-thirds of the patients had chronic heart failure and presented with an acute deterioration. The date of the first UK coronavirus death, 2 March 2020, was the cut-off to define two groups: before-COVID (7 January to 2 March; eight weeks) and after-COVID (3 March to 27 April; eight weeks; i.e. during the pandemic).

There was a substantial, but statistically non-significant, drop in admissions for acute heart failure during the pandemic. A total of 164 patients were admitted in the eight weeks before-COVID compared to 119 patients after-COVID - a 27% reduction (p=0.06).

"This finding may reflect public concerns about social distancing at the start of the national lockdown, delayed reporting of symptoms, and anxiety regarding hospital attendance," said Dr. Dastidar. "In support of these explanations, our data demonstrate an increase in referrals during the later weeks of lockdown in line with UK media reports encouraging patients to seek medical attention if needed."

The 30-day mortality rate of patients with acute heart failure nearly doubled during the pandemic. Some 11% of patients in the before-COVID group died within 30 days compared to 21% of the after-COVID group - a relative risk of 1.9 (95% confidence interval 1.09-3.3).

The researchers examined what factors may have been responsible for the higher death rate during the pandemic. Older age and admission during the pandemic were linked with death after adjusting for other factors that could influence the relationship, with hazard ratios of 1.04 and 2.1, respectively. When patients with a positive COVID test were removed from the analysis, there was no difference in mortality between the before- and after-COVID groups - indicating that patients with both acute heart failure and COVID-19 had a poorer prognosis.

"This may suggest a direct interaction or susceptibility to worse outcomes for acute heart failure patients with superimposed COVID infection," said Dr. Dastidar. "It is noteworthy that our region had very low rates of COVID infection during the study and yet a connection with higher mortality was still apparent."

Dr. Dastidar pointed out that routine testing for COVID-19 infection was not in place at the time of the study. He said: "It would be informative to review more recent admissions when COVID testing was more widely implemented to further support our findings. As this was a single centre study, it would be valuable to confirm the findings in a countrywide analysis. Additionally, we are keen to review longer term data to look for patterns of prognosis at later stages in this patient population."

WHO H. Gilbert Welch MD, MPH, Senior Investigator, Center for Surgery and Public Health, Brigham and Women's Hospital; co-author of a new Sounding Board article published in The New England Journal of Medicine.

WHAT Melanoma of the skin is now the third most commonly diagnosed cancer in the U.S. Diagnoses of melanoma are six times as high today as they were 40 years ago. While incidence of melanoma has been rising steeply, melanoma mortality has been generally stable. In a Sounding Board article, Welch and colleagues present evidence for why they believe that increased diagnostic scrutiny is the primary driver of the rapid rise in melanoma diagnoses.

"Melanoma is now the posterchild for overdiagnosis," said Welch. "Although the conventional response has been to recommend regular skin checks, it is far more likely that more skin checks are the cause of the epidemic -- not its solution."

Among many examples, Welch and co-authors describe a study in which nine dermatopathologists reviewed skin-biopsy specimens used for diagnosis 20 years earlier. Many of the specimens previously diagnosed as benign were now diagnosed as melanoma. Welch and co-authors also share data showing that among the Medicare population, the proportion of beneficiaries biopsied increased every year from 2004 to 2017, nearly doubling over that time. Over the same period, the incidence of melanoma in adults 65 and older also doubled.

The authors point out that there are many potential harms in over-diagnosing melanoma, from the immediate -- scarring, wound infection, out-of-pocket costs -- to longer term effects such as impeding access to care for people with symptomatic skin diseases.

"Despite the best of intentions by all parties, increased diagnostic scrutiny can produce a cycle of increasing overdiagnosis and intervention in any disease with a reservoir of subclinical forms. Melanoma is no exception," the authors write. "The economic disruption caused by Covid-19 obliges clinicians to protect people from the financial stress of needlessly being turned into a patient."

CLEVELAND - In a new paper, researchers describe their development of a near-real time spatial assessment of COVID-19 cases to help guide local medical responses to clusters of outbreaks of the virus at the local level.

The paper, entitled "Geographic monitoring for early disease detection (GeoMEDD)," appeared in the Dec. 10 issue of Nature Scientific Reports and comes from researchers at Case Western Reserve University (CWRU) School of Medicine, University Hospitals (UH) Cleveland Medical Center, and Texas A & M University.

While developing a tracking system during the beginning stages of the COVID-19 pandemic, the authors realized that there was a need to refocus more traditional spatial mapping towards a more granular cluster detection methodology that provides syndromic surveillance, or early indicators of emergent disease by leveraging a health system's access to data streams from various sources which account for location and timing of cases.

"Without such integration, there are missed opportunities for hospitals, health departments, and community leaders to mobilize early intervention activities and save lives. This information provides insights to targeted community testing opportunities, post-acute care intervention, and targeted community education in areas with community spread," said lead author Andrew Curtis, PhD, Co-Director of the GIS Health & Hazards Lab and Professor in the Department of Population and Quantitative Health Sciences at the CWRU School of Medicine.

"From a hospital and health system perspective, such disease propagation can rapidly tax capacity and resources. From a humanitarian dimension, being able to communicate with local communities, municipality or even building managers requires both time and space insights," said Curtis.

The authors propose, for example, that positive COVID-19 test results could be analyzed in real time as they flow into a health system, which when combined with severity of the associated symptoms, details such as age and previous medical histories of the patient, and the background neighborhood "risk" could all be added to provide a contextualized understanding of not only where disease occurs but why, and where it is likely to spread next.

"Early detection is critical to interception and potential spread of disease, and is helpful at identifying areas of vulnerability so that efforts can be adequately prioritized," said Jayakrishnan Ajayakumar, PhD, Lab Manager of the GIS Health & Hazards Lab in the Department of Population and Quantitative Health Sciences at the CWRU School of Medicine, who developed the necessary software. "The tracking system also helps prepare medical and first response teams for potential surge planning."

GeoMEDD does not replace traditional forms of disease cluster detection, rather it enhances investigation in near real-time and in the context of health system operations to a dynamic situation.

"Syndromic surveillance interest lies in the first case in a post-acute care home, or the timing pattern of emerging positives in an apartment complex, or along a rural street, or how houses on city streets 'emerge' suggesting a local transmission mechanism," said Maulik Purohit, MD, MPH, Associate Chief Medical Information Officer at UH. "With this information, teams can mobilize to minimize the spread. This methodology will be relevant for many infectious diseases and operational responses, not just COVID."

By identifying these emergent patterns in the continuous data streams available to health systems, rational and evidence-based strategies could potentially be used to reduce further transmission.

"COVID spreads very efficiently in congregate housing and narrowing the time lag between knowledge of an emergent case and implementation of evidence-based interventions could help to save lives," said Justin Yax, DO, Director of Population Health, Department of Emergency Medicine at UH.

These data have also been helpful to local health departments and community leaders and has gained interest and support from the state.

While contact tracing remains a vital part of understanding disease spread, the clusters described here reveal geographic patterns and aspects of diffusion in near real time -- much sooner than other public health monitoring currently available in the region.

While COVID-19 provided the stimulus for these new method developments, the application extends far beyond this pandemic to potentially other future epidemics, to regular flu seasons, to outbreaks of overdoses, and to surveillance looking for bioterror or radiological symptoms.

"GeoMEDD should be seen as the first step in the development of a suite of clusters nuanced to varying geographies (urban versus rural, even vertical living environments), or specific topics," said Jacqueline Curtis, PhD, Co-Director of the GIS Health & Hazards Lab and Associate Professor in the Department of Population and Quantitative Health Sciences at the CWRU School of Medicine.

DALLAS - Jan. 6, 2020 - UT Southwestern scientists have developed a new method to study the molecular characteristics of T cells, critical immune cells that recognize and attack invaders in the body such as viruses, bacteria, and cancer.

The approach, described today in the journal Nature Methods, enables researchers to more easily analyze the roles of T cell receptors (TCRs) - the molecules on the surfaces of T cells that are responsible for recognizing pathogens.

"This could lead to a better understanding of how T cells work as well as new ways to harness T cells to fight disease," says study leader Tao Wang, Ph.D., assistant professor of population and data sciences and a member of the Quantitative Biomedical Research Center at UTSW.

While some immune cells can simultaneously attack different pathogens, T cells are more targeted - every individual T cell has a distinct set of T cell receptors (TCRs) on its surface. Each receptor usually recognizes only one specific molecule, or "antigen." One TCR, for instance, might bind only to a protein found in lung cancers, while a different TCR might bind just to an influenza virus. When a T cell encounters an antigen that binds to one of its TCRs, it becomes activated, prompting an immune response. To ward off the diverse set of potential invaders, humans have millions of different T cells in their bodies.

Scientists have attempted to study what makes different T cells and TCRs more or less effective, hampered so far by a lack of information about what various TCRs do. Generally, they assume that TCRs that look alike must bind to similar antigens, and that all TCRs activate T cells in a similar way.

To eliminate this guesswork, the research team developed a statistical model combining two existing technologies: TCR analysis, which measures a person's TCR diversity, and single-cell RNA sequencing, which identifies the particular genes that are turned on or off in a T cell. Combining these technologies has been challenging since they both generate many thousands of pieces of data per experiment, and the data comes in two different forms. The new model, dubbed Tessa, uses powerful statistical methods to bridge this gap. Tessa reveals what happens to an individual T cell when its TCR recognizes an antigen, and in what way TCRs impact the function of the T cells. (Tessa stands for TCR functional landscape estimation supervised with scRNA-sequencing analysis.)

Using Tessa, the researchers studied 100,288 T cells from both healthy people and cancer patients. In cancer patients, they discovered that the variety of TCRs in T cells has a weaker influence on the functional status of T cells than on those found in healthy patients. This is likely because a plethora of other immune molecules, secreted into the tumor micro-environment, are influencing T cell activity in other ways. This observation - and others that are likely to result from more widespread use of Tessa - could have implications for scientists designing immune-based cancer treatments.

David Gerber, M.D., professor of internal medicine and population and data sciences, and associate director of clinical research in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, believes this work provides a completely new way of using single T cell sequencing data. "We envision deploying this promising tool to study the roles of T cells in immune-related adverse events caused by cancer immunotherapy through a recently funded NIAID U01 award," he says.

"Previous techniques have involved a lot of guessing when it comes to the exact function of T cells and how T cell receptors associate with function," adds Todd Aguilera, M.D., Ph.D., a UTSW assistant professor of radiation oncology, and an expert in immunotherapy, who is also collaborating with Wang. "I believe this method could help the identification of the most promising TCRs for personalized TCR-based immunotherapy and better define productive immune responses to guide identification of the optimal immunotherapy strategies."

Using a blood test, a German-Dutch research team has predicted the risk of Alzheimer's disease in people who were clinically diagnosed as not having Alzheimer's disease but who perceived themselves as cognitively impaired (Subjective Cognitive Declined, SCD). The researchers analyzed blood samples from an SCD cohort supervised at the Alzheimer Center Amsterdam. Using a test developed at Ruhr-Universität Bochum (RUB) called the Immuno-Infrared Sensor, they identified all 22 subjects at study entry who developed Alzheimer's dementia, thus the clinical symptoms, within six years. The test also showed which subjects were at very low risk to develop Alzheimer's dementia within six years. The team describes the results in the journal Alzheimer's Research and Therapy, published online 24 December 2020.

For the study, the team led by biophysics Professor Klaus Gerwert and Julia Stockmann of the Bochum Research Center for Protein Diagnostics (Prodi) collaborated with RUB statistician Professor Nina Timmesfeld, Department of Medical Informatics, Biometry and Epidemiology, and researchers from the Amsterdam University Medical Centers, Location Vrije University (VUmc) led by Professor Charlotte Teunissen and Professor Philip Scheltens.

Sensor detects misfolded proteins in blood

The SCD cohort included 203 individuals. At study entry, blood samples were taken from all the participants and analyzed using the patented immuno-infrared sensor that detects misfolding of the amyloid-beta (Aβ) peptide, which is a biomarker for Alzheimer's disease. In addition, the subjects underwent extensive Alzheimer's disease diagnostic testing; at study entry, this did not provide a diagnosis of Alzheimer's disease in any of the subjects studied. The immuno-infrared sensor, on the other hand, detected misfolded Aβ peptides at study entry in all 22 subjects who developed the clinical disease in the following six years. In subjects who showed mild misfolding, it took on average longer (3.4 years) for conversion to clinical Alzheimer than in subjects with severe Aβ misfolding (2.2 years).

Together with statistician Nina Timmesfeld, the researchers predicted the risk of developing clinical Alzheimer's disease. According to the statistical model, SCD subjects with mild misfolding have an 11-fold higher risk and SCD subjects with severe misfolding have a 19-fold higher risk of developing clinical Alzheimer's in the following six years than subjects without misfolded Aβ peptide. "Misfolding of Aβ is therefore a very precise prognostic plasma biomarker," concludes Klaus Gerwert.

Combination of two biomarkers further improves prognosis

In addition, the team checked whether the combination of two different measurement methods in the plasma biomarker panel could further improve the prediction of disease risk. For this purpose, they combined the misfolding of all Aβ isoforms with a concentration decrease for Aβ42 as ratio to Aβ40 in plasma. The Amsterdam group measured Aβ concentrations using the new single-molecule array (SIMOA) technology. This increased the assay accuracy from an AUC (area under the ROC curve) of 0.94 to 0.99.

"We can now very accurately predict the risk of developing clinical Alzheimer's disease in the future, with a simple blood test on symptom-free individuals with subjective concerns," explains Klaus Gerwert. "However, we can just as confidently give the all-clear for SCD patients who have a very low probability of developing Alzheimer's disease in the next six years."

"Through the plasma biomarker panel, we can monitor disease progression over 14 years, beginning in the asymptomatic state with misfolding of Aβ and subsequent plaque deposition of Aβ42 in the brain associated with the first cognitive impairments," Julia Stockmann adds.

Hope for early-stage treatment

Such a blood test, which can detect the onset of Alzheimer's dementia even in the asymptomatic state, would be particularly useful if an active substance were available to treat the disease. In March 2021, the U.S. Food and Drug Administration will decide whether to approve the drug aducanumab. "Our results indicate that Alzheimer's drugs should be applied as early as possible in a non-clinical stage to improve therapy response," Klaus Gerwert said. The Bochum researcher is promoting the immuno-infrared sensor to be used in the selection of trial participants in the future to achieve a significantly better therapy response.

Naturopathic medicine, or herbal medicine, is all the rage, especially among young people. But how much of this is supported by science?

Ginger is known to have anti-inflammatory and anti-oxidative effects, making it a popular herbal supplement to treat inflammatory diseases.

And according to a Michigan Medicine led study published in JCI Insight, the main bioactive compound of ginger root, 6-gingerol, is therapeutic in countering the mechanism that fuels certain autoimmune diseases in mice. Researchers specifically looked at lupus, a disease which attacks the body's own immune system, and its often associated condition antiphospholipid syndrome, which causes blood clots, since both cause widespread inflammation and damage organs overtime.

In mice with either antiphospholipid syndrome or lupus, 6-gingerol prevented neutrophil extracellular trap release, which is triggered by the autoantibodies that these diseases produce.

"Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils," says lead author Ramadan Ali, Ph.D. "These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil's surface."

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The study question was, "will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?"

"This pre-clinical study in mice offers a surprising and exciting, 'yes'," Ali says.

Ali discovered that after giving 6-gingerol, the mice had lower levels of NETs. Their tendency to make clots was also drastically reduced and 6-gingerol appeared to inhibit neutrophil enzymes called phosphodiesterases, which in turn reduced neutrophil activation.

But the most surprising find of all was that the mice, regardless of whether they had antiphospholipid syndrome or lupus, had reduced autoantibodies suggesting the inflammatory cycle, autoantibodies stimulating NETs which stimulate more autoantibodies, was broken.

Next steps and potential implications

"Through my years of medical training I wasn't taught much about supplements, but it's something that so many patients ask me about," says study author and rheumatologist Jason Knight, M.D. "When Ramadan brought the concept to me, I was enthusiastic to pursue it in my lab, as I knew it would matter to them. Sometimes our patients give us really good ideas!"

Although the study was done in mouse models, Ali and Knight think the preclinical data, showing that 6-gingerol has anti-neutrophil properties that may protect against autoimmune disease progression, encourages clinical trial development.

"As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol," Knight says. "It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit."

The bioactive compound can't be the primary therapy for someone with active antiphospholipid syndrome or lupus, but the team is interested to see if the natural supplement may help those at high risk for disease development.

"Those that have autoantibodies, but don't have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice," Ali says, who's passionate about natural medicine research for rheumatic diseases.

"Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?"

Cardiovascular disease is the leading cause of death associated with smoking cigarettes. But as use of e-cigarettes ("vaping") becomes more popular, including as a way to cut back on cigarettes, little is known about its effect on cardiovascular health.

Now, a new Boston University School of Public Health (BUSPH) study, published in the journal Circulation, finds that vaping may not cut risk of cardiovascular disease in the way that most adults use them--in combination with cigarettes.

"Dual use of cigarettes and e-cigarettes appears to be as harmful to cardiovascular health as exclusive cigarette smoking," says study lead author Dr. Andrew Stokes, assistant professor of global health at BUSPH.

Stokes notes that an estimated 68% of people in the US who vape also smoke traditional cigarettes. "If e-cigarettes are used in quit attempts, cigarette smoking should be completely replaced, and a plan to attain freedom from all tobacco products should be advised," he says.

Stokes and colleagues from the American Heart Association Tobacco Regulation and Addiction Center used data on 7,130 participants in the 2013-2014 first wave of the nationally-representative PATH (Population Assessment of Tobacco and Health) study.

The long lag time between tobacco exposure and cardiovascular disease makes it difficult to evaluate how newer products, such as e-cigarettes, affect cardiovascular health. So, the researchers instead looked for cardiovascular inflammation and oxidative stress, biomarkers that are known predictors of cardiovascular events such as heart attacks and heart failure.

They found that study participants who exclusively vaped were no more likely to have cardiovascular inflammation or oxidative stress than participants who didn't smoke or vape. But participants who both smoked and vaped were no less likely to show these biomarkers than participants who exclusively smoked traditional cigarettes.

The researchers then conducted extensive sensitivity analyses to account for other related risks, including use of other tobacco products, marijuana use, and secondhand smoke exposure. In all of these analyses, the results were the same: Dual use of e-cigarettes and traditional cigarettes showed the same level of predictors of cardiovascular disease as exclusively smoking.

"The finding that the levels were similar between exclusive e-cigarette users and non-users (no cigarettes or e-cigarette use) is unexpected," Stokes says, "but exclusive e-cigarette use was rare in our sample, so additional studies are needed.

"We do know that a variety of harmful or potentially harmful constituents have been found in e-cigarette aerosols--such as volatile organic compounds, polycyclic aromatic hydrocarbons, and metals--albeit with lower concentrations compared to cigarettes, so using these products is not without risks."

A growing body of research points to other areas of health harmed by vaping. In another recent study, published in JAMA Network Open, Stokes and colleagues found that vaping alone can increase the risk of respiratory disease by more than 40%.

Irvine, Calif., Jan. 6, 2021-- In the United States, Black, Latino and low-income communities have historically lacked nearby access to pharmacy services. To provide the first record of these "pharmacy deserts" in Los Angeles County, a University of California, Irvine study identified communities where the nearest pharmacy was at least one mile away.

Unlike previous studies, this one describes pharmacy deserts in terms of social determinants of health - such as owning a vehicle, crime rates and poverty - to determine which communities have the greatest need for pharmacy access. Published in the Journal of Racial and Ethnic Health Disparities, it is the first study to look at pharmacy deserts in the state of California.

"My goal is to bring these concepts together at the intersection of pharmacy practice, public health and social justice to reduce health disparities," said Cheryl Wisseh, a health sciences assistant clinical professor of clinical pharmacy practice at UCI and the study's first author.

The study was conducted in collaboration with researchers at Charles R. Drew University of Medicine and Science in Los Angeles.

They found that some Los Angeles County areas lacking pharmacy access are characterized by denser populations, larger numbers of Latino and Black residents, less vehicle and home ownership, higher crime rates, and greater poverty.

"These social determinants of health compound the negative effects of pharmacy shortage through competing needs," Wisseh said. "For example, some residents living below the poverty line may choose to forgo picking up their medications so that they can pay for food, rent and other necessities."

A pharmacy shortage likely equates to fewer clinical pharmacy services, such as health screenings, vaccines and medication management, Wisseh added.

Since pharmacies are a large distributor of vaccines across the U.S., the COVID-19 pandemic makes access to pharmacists even more pressing.

"As the COVID-19 vaccines start rolling out, pharmacists will be key to the rapid and equitable distribution and administration of doses, just as they have been with COVID-19 testing," said Jan D. Hirsch, founding dean of the UCI's School of Pharmacy & Pharmaceutical Sciences.

Wisseh added that the communities within pharmacy deserts are particularly vulnerable to COVID-19.

"The same forces of structural inequity and systemic racism that contribute to the formation of Los Angeles pharmacy deserts contribute to the disproportionate test positivity, incidence and mortality rates of COVID-19 in racial and ethnic minorities," she said.

"Residents in Los Angeles County pharmacy deserts might benefit greatly from equitable, innovative, community-based interventions that increase access to medications, pharmacy services and pharmacists," the researchers wrote in the study. For instance, the county could add pharmacists to local clinics and other primary care settings to provide clinical services. In her own clinical practice, Wisseh works with county-led programs in South Los Angeles to improve pharmacy access for patients.

Wisseh plans to conduct a similar study on a larger scale - perhaps across California - to examine how pharmacy deserts contribute to whether minority communities take medications as prescribed and investigate disparities in available medications within pharmacies.

A study led by University of Ottawa researchers provides empirical evidence that mindfulness has a significant impact on the brain of women suffering from neuropathic pain related to breast cancer treatment. The researchers showed that mindfulness-based stress reduction (MBSR) helps modulate neuropathic pain.

Their findings could make a difference in the lives of many women. In Canada, over a quarter of a million women are expected to be diagnosed with breast cancer - the most diagnosed cancer among women worldwide - in 2020. In addition to the psychological impacts of breast cancer, approximately 20 to 50 percent of survivors report experiencing chronic neuropathic pain following treatment.

We talked to senior author Dr. Andra Smith, Full Professor at the uOttawa School of Psychology, to learn more about the most recent findings published in the journal Mindfulness.

Why did you and your team decide to look at mindfulness to improve pain-related problems?

"Neuropathic pain is a very common side effect of chemotherapy and other breast cancer treatments. Pain killers do not always work and quality of life, cognitive abilities, and overall well-being can be reduced due to this pain. Due to these negative effects and the complexity of treatment for this type of pain following breast cancer treatment, it is important to provide adjunct treatment and management options.

We have heard a lot about mindfulness over the past few years, about how it helps people relax and feel better. If mindfulness, a non-pharmacological tool, can be used to help with neuropathic pain, women will feel better and might not experience such disruptive pain.

Pain is a subjective experience and mindfulness is often dismissed as a "buzz word." But our research provides objective, empirical evidence of a significant impact of mindfulness on the brain of these women."

How was the research conducted?

"We investigated the impact of an 8-week mindfulness-based stress reduction (MBSR) program on emotional reactivity among a sample of breast cancer survivors with chronic neuropathic pain. We used state-of-the-art brain imaging at The Ottawa Hospital, on their 3T MRI scanner and collected data on white matter health, brain activity during emotional pain related word processing and during resting state.

Women with neuropathic pain were imaged before and after an MBSR program, or treatment as usual. Pain, quality of life, and imaging were compared between the two groups and within the MBSR group pre- and post-MBSR."

What did you find?

"We observed major reductions in brain activity following mindfulness-based stress reduction in regions related to pain, emotional regulation, and cognitive processing. Both pain severity and pain interference, for the MBSR group, were significantly reduced after the 8-week training.

Our results show a significant improvement in brain health as well as in pain perception.

There are many anecdotal reports of how this or that made a person "feel better" but the really exciting results here are that we can see that there are actual changes in the brain and the way a person can alter their response to pain."

Why is it important?

"This research provides hope for a non-invasive method of easing the struggle of chronic neuropathic pain in women following breast cancer treatment.

Pain is something that people fear, and many people run into significant secondary problems because of their pain medication use, including drug misuse and mental health issues. Mindfulness has a neurophysiological effect that can alter one's perception of pain.

This research shows that there are adjunctive treatment options. If used properly, the information we have published can improve health outcomes for the people involved and could potentially also reduce health costs, as well as some of the related problems - particularly those related to mental health."

Who worked on this research?

"Dr. Patricia Poulin, at The Ottawa Hospital, was the clinical principal investigator with her research team of Heather Romanow, Yaad Shergill, Emily Tennant, and Eve-Ling Khoo. This included recruitment of the women and all clinical assessments.

My lab performed the scanning component of the study, including my imaging team of Dr. Taylor Hatchard, Ola Mioduszewski and Dr. Lydia Fang.

The data was collected over two years, from 2017 to 2019, funded by both Canadian Institutes of Health Research (CIHR) and Canadian Breast Cancer Foundation grants. We published three articles on our research in the last four months. The latest, "Reduced Emotional Reactivity in Breast Cancer Survivors with Chronic Neuropathic Pain Following Mindfulness-Based Stress Reduction (MBSR): an fMRI Pilot Investigation" was published in November 2020 in the journal Mindfulness."

Other papers related to this research:
Breast cancer survivors living with chronic neuropathic pain show improved brain health following mindfulness-based stress reduction: a preliminary diffusion tensor imaging study

Mindfulness-based stress reduction alters brain activity for breast cancer survivors with chronic neuropathic pain: preliminary evidence from resting-state fMRI

Indianapolis, Ind. - A team of researchers led by the Indiana Biosciences Research Institute Diabetes Center's Scientific Director Decio L. Eizirik, MD, PhD, has found that identifying new treatments for autoimmune diseases requires studying together the immune system AND target tissues. This study, "Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis and rheumatoid arthritis," is featured in the Jan. 6, 2021, edition of Science Advances.

"We must move away from the present "immune-centric-only" view of autoimmune diseases," explains Eizirik. "Indeed, trying to understand these diseases focusing on the immune system only, and forgetting the target tissues, may be similar to attempting to fly a plane with only one wing."

Autoimmune diseases, which affect up to 5 percent of the population in different regions, suffer from a case of mistaken identity. The immune system is supposed to protect us from infectious diseases or tumors. Yet, during autoimmune diseases the immune system mistakenly attacks and destroys components of our body, which then causes, for example, type 1 diabetes (T1D), systemic lupus erythematosus (SLE), multiple sclerosis (MS) or rheumatoid arthritis (RA). These four autoimmune diseases share almost half of the same genetic risks, chronic local inflammation and mechanisms leading to target tissue damage.

Despite these common features, autoimmune disorders are traditionally studied independently and with a focus on the immune system rather than on the target tissues. Knowing that there is increasing evidence that the target tissues of these diseases are not innocent bystanders of the immune system attack, but instead are active participants, Eizirik and his team hypothesized that key inflammation-induced mechanisms, potentially shared between T1D, SLE, MS and RA, may drive similar molecular signatures at the target tissue level.

"This research is significant in reaching the JDRF's mission to cure, treat and prevent T1D," said Frank Martin, Ph.D., JDRF director of research. "Discovering the common pathways of tissue destruction across multiple autoimmune diseases will dramatically accelerate our path to a cure for T1D. Drugs that are effective in one autoimmune disease could be equally beneficial for another and quickly repurposed to make a big impact for people living with that disease. Characterizing the similarities and differences between multiple autoimmune diseases has the potential to transform the way we treat and cure these diseases in the future."

To test this hypothesis, the research team obtained gene expression data from diseased tissue sampled from controls or individuals affected by T1D, SLE, MS and RA. This indicated major common gene expression changes at the target tissues of the four autoimmune diseases evaluated. One candidate gene in common between the four diseases is TYK2, a protein that regulates interferon signaling. The team showed in its research that use of TYK2 inhibitors - already in use for other autoimmune diseases - protect β-cells against immune-mediated damage. This finding reinforces the importance of studying the target tissue of autoimmune diseases, in dialogue with the immune system, to better understand the genetics and natural history of these devastating diseases and to identify novel therapies.

The authors of this study include:

Decio L. Eizirik, Indiana Biosciences Research Institute, Indianapolis, IN, USA and Université Libre de Bruxelles, Brussels, Belgium

Florian Szymczak, Université Libre de Bruxelles, Brussels, Belgium

Maikel Colli, Université Libre de Bruxelles, Brussels, Belgium

Mark Mamula, Yale University School of Medicine, New Haven, USA

Carmella Evans-Molina, Indiana University School of Medicine, Center for Diabetes and Metabolic Diseases, Indianapolis, IN, USA

Researchers at Rush University Medical Center have found that opioid use might increase a person's risk of developing pancreatic cancer.

Published Jan. 6, the study, titled "Opioid Use as a Potential Risk Factor for Pancreatic Cancer in the United States," is the first in the country to show evidence that opioid use may be an unidentified risk factor contributing to the increasing incidence of pancreatic cancer.

In fact, opioid misuse and overdose have evolved into a public health crisis. Approximately 70,000 drug overdose deaths were reported in 2017, 68% of which involved an opioid.¹ The use of prescription opioids for the management of chronic pain has increased remarkably, with more than 191 million opioid prescriptions given to patients in the United States in 2017. Not surprisingly, the opioid addiction rates among patients who are given opioid for chronic pain have increased, with 29% of such patients misusing opioids, and 12% developing an opioid use disorder.²

Pancreatic cancer rates also are increasing in the United States. Opioids have been shown to have a harmful effect on multiple types of cancer with recent data suggesting opium use as a possible risk factor for pancreatic cancer in West Central Asia. Population-based studies have suggested opium use to increase risk of pancreatic cancer in a dose dependent manner.³?? While opium use is not a common recreational habit in the United States, opioid use has been rising remarkably over the past decade.

Faraz Bishehsari, MD, PhD, the corresponding author of the study, and his team aimed to examine the possible association between the pattern of opioid use and the changes in the rates of pancreatic cancer during the years 1999-2016. Using the Center for Disease Control's Wonder online data (procured from the Vital Statistics Cooperative Program) the team extracted the opioid death rate as a surrogate for prescription and illicit opioid use. Incidence of pancreatic cancer was retrieved from the CDC's online database gathered from the U.S. Cancer Statistics Working Group. They extracted the pattern of the lifestyle and behavioral factors that over time could potentially affect the risk of pancreatic cancer.

Usman Barlass, MD, Ameya Deshmukh, PhD, and Todd Beck, MD, worked with Bishehsari on the study. Using national datasets, the team evaluated whether the trend in opioid usage could explain increasing pancreatic cancer diagnoses at the national and state levels over time after correcting for the potential confounding factors. They found that both pancreatic cancer and opioid death rates rose over time at the national and state levels. A prior state's opioid death rate significantly predicted the trend in the incidence of pancreatic cancer years after and had a significant effect on the estimated annual change in the rate of this cancer.

The collected data suggests a link between opioid consumption and the risk of pancreatic cancer. The next step to directly establish the role of opioids as a novel risk factor for pancreatic cancer is to conduct large population-based studies or longitudinal datasets that reliably register long-term outcomes in opioid users. Findings from the current study, once confirmed by the individual-level data on opioid consumption and risk of pancreatic cancer, could have direct clinical relevance by considering non-narcotic (alternative) pain control approaches in these patients.

The team proposes to investigate possible mechanisms that may link opioid use to the development and/or progression of pancreatic cancer. Consistent with the current findings, a recent post hoc analysis of two randomized controlled trials of patients with advanced cancers (including pancreatic cancer), revealed that that those treated frequently with an opioid antagonist had significantly improved overall survival compared to placebo.?

"Our mechanistic studies could provide further insights on the pathways that opioid could potentially impact progression of cancer," Bishehsari added.

Related to new research published in the January issue of Science Translational Medicine, Patrick McNutt, PhD, of the Wake Forest Institute for Regenerative Medicine, was part of the research team that demonstrated a new "Trojan horse" approach that produces strong antidotal efficacy in treating lethal botulism in mice, guinea pigs and rhesus macaque monkeys.

Furthermore, in a companion article, an independent team demonstrated that a related drug has robust efficacy in mice.

"This is one of those serendipitous moments in science where two groups, working independently, demonstrate similar results for a long-standing problem," McNutt said. "We are currently modifying this drug to enhance its therapeutic properties against botulism and exploring whether the same approach can be repurposed to treat other neuronal diseases."

In 2010, Konstantin Ichtchenko (New York University School of Medicine) conceived of a novel 'trojan horse' strategy to treat botulism. This strategy is based on using a non-toxic form of BoNT to deliver therapeutic antibodies to paralyzed neurons, blocking wild-type toxin activity and accelerating recovery from paralysis. Over the past decade, Konstantin established collaborations with Patrick McNutt (Wake Forest Institute of Regenerative Medicine), Phil Band (Cytodel, Inc.) and Chuck Shoemaker (Tufts University) to develop and test this new drug in a variety of experimental models.

Botulinum neurotoxins (BoNTs) are a family of bacterial poisons responsible for the clinical disease known as botulism. BoNT acts within nerve terminals to destroy proteins necessary for evoking muscle contraction, causing muscle paralysis that develops into respiratory arrest at lethal concentrations. BoNT is the most poisonous substances known, with median lethal doses that are over a million-fold lower than cyanide.

Because of its extraordinary potency and long duration of action, the toxin is considered a Tier 1 agent by the CDC, which is reserved for the most dangerous public threats. These same properties render BoNT a highly effective cosmetic and therapeutic drug (e.g., BOTOX) with diverse clinical indications. Despite decades of effort, there are no antidotes for the life-threatening consequences of botulism. This failure is primarily because the toxin hides within the nerve terminal, where it poses a challenging target for delivery of therapeutic molecules.