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PHILADELPHIA (March 9, 2020) - While firearm violence is a major public health challenge in the United States, it has often been considered a law enforcement issue with only law enforcement solutions. An article by two University of Pennsylvania researchers advises that treating firearm violence as a disease and taking a public health approach to prevention and treatment can help reduce its harms.

Key to achieving that goal will be to overcome legislative mandates around research funding which have hampered investigators from establishing careers studying firearm violence and building a body of evidence. An important step this year is the allocation of $25 million in the federal budget to NIH and CDC specifically targeted to the study of firearm violence.

"Federal funding around firearm violence research lags far behind the burden of disease," says Therese S. Richmond, PhD, RN, FAAN, the Andrea B. Laporte Professor of Nursing and Associate Dean for Research & Innovation at the University of Pennsylvania School of Nursing (Penn Nursing). The consequences of firearm violence are broad and deep for individuals, families, and communities.

"Reducing the impact of firearm violence is contingent upon building a solid evidence base. Without this base, effective interventions may be under-used and ineffective ones may waste our collective time and money," says co-author Elinore J. Kaufman, MD, MSHP, from Penn's Perelman School of Medicine. Both Kaufman and Richmond are affiliated with the Penn Injury Science Center, which brings together university, community, and government partners around injury and violence intervention programs.

The article details how critical care providers can analyze the intersections among individuals, firearms, and environments across the continuum of care, and how public health research can design, test, and implement effective interventions at the environmental, policy, technological, and individual levels to prevent firearm violence. "Health care providers are perfectly positioned to change the current political diatribe from pro-gun/anti-gun to how we can systematically study approaches and implement evidence to reduce injury and death as we do with other diseases," says Richmond. The article, "Beyond Band-Aids for Bullet Holes: Firearm Violence As a Public Health Priority," has been published in the journal Critical Care Medicine.

Recently, Richmond presented the William Shoemaker Honorary Lecture on the impact of gun violence on public health during the Society of Critical Care Medicine's 49th Annual Critical Care Congress in Orlando, Florida. You can view a recording of the presentation here.

What The Study Did: This randomized clinical trial investigated if gabapentin, a drug often used to treat nerve pain, would be useful in the treatment of patients with alcohol use disorder (problem drinking that becomes severe) and a history of alcohol withdrawal symptoms. As many as 30 million people in the U.S. meet criteria for alcohol use disorder, yet less than 1 million receive medication that may be beneficial.

Authors: Raymond F. Anton, M.D., of the Medical University of South Carolina in Charleston, 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/jamainternmed.2020.0249)

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

What The Study Did: Findings in this observational study of almost 387,000 children born in the U.S. don't show evidence of an association between rotavirus vaccination (routinely recommended for all infants by age 8 months) and type 1 diabetes in children who were followed over a range of about 5 years. Researchers explain limitations of the study, as well as two potential unmeasured confounding variables that may have affected results.

Author: Jason M, Glanz, Ph.D., of the Institute for Health Research at Kaiser Permanente Colorado in Aurora, 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/jamapediatrics.2019.6324)

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

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Media Advisory: The full study is linked to this news release.

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New Rochelle, NY, March 9, 2020--A new study found that two-thirds of female adolescents ages 16-21 seen in a pediatric Emergency Department (ED) were interested in discussing contraception, despite having a high rate of recent visits to a primary care provider. More than 22% indicated that they would be likely to start or change contraception during the ED visit. Is the ED a "Golden Opportunity" for contraceptive education and initiation, ask the authors of this study in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through April 10, 2020.

The article entitled "Identifying a Golden Opportunity: Adolescent Interest in Contraceptive Initiation in a Pediatric Emergency Department" was coauthored by Colleen Gutman, MD and Atsuko Koyama, MD, MPH, Emory University, David Dorfman, MD and Patricia Kavanagh, MD, Boston University School of Medicine, and Halea Meese, University of Colorado School of Medicine.

Among the 381 women surveyed, 80.5% had been sexually active with a male partner and 28.2% had previously been pregnant. Thirty-nine percent of the women were currently using hormonal contraception, and 57.2 % were satisfied with their current method of contraception. Based on their findings, the researchers concluded that the ED provides an important opportunity to discuss and initiate effective contraception for young women.

The accompanying Editorial entitled "Contraception Provision in the Emergency Department: Are We Ready to Overcome the Obstacles?" details the challenges to providing contraceptive care in the ED, but concludes: "Despite these barriers, the benefits to providing contraception are undeniable." Obstacles include the variation in provider comfort with discussing contraceptive options, the training required for placing long-acting reversible contraception, such as implants, billing and insurance issues, and concerns related to parental and provider acceptance.

Editorial coauthors Kayleigh Fischer, MD, Washington University in Saint Louis School of Medicine, and Lauren Chernnick, MD, Columbia University Medical. Center, conclude, "If we can design novel ways to weave contraceptive provision in to the ED workflow, such as using technology or outside assistance such as health educators, we may be closer to finding the middle ground in which our female patients are receiving the evidence-based, patient-centered reproductive counseling they not only need but deserve."

Early-career family physicians who both provide maternity care and prescribe buprenorphine--a medication used to treat opioid use disorder--primarily completed their training in a small number of residency programs. Using data from the 2016, 2017 and 2018 National Family Medicine Graduate Survey, administered annually by the American Board of Family Medicine, the research team behind this study asked clinicians who graduated from family medicine residency programs within the past three years whether "maternity care" or "buprenorphine treatment" were part of their practice and whether they were currently delivering babies. Of the 5,103 respondents in their sample, 153 both deliver babies and prescribe buprenorphine. A further 108 respondents provide maternity care and prescribe buprenorphine but do not perform deliveries. The researchers note that it is not clear whether the surveyed physicians are necessarily providing pregnancy care and prescribing buprenorphine to the same patients.

Of 614 total family medicine residencies represented in the survey, only 15 of them, mostly in urban areas on the East and West Coasts, trained 25% of the respondents who provide this care. As data about the risks of maternal mortality from substance use disorder emerges, it will be important to increase training opportunities in family medicine residencies to meet the needs of pregnant women with substance use disorder.

The new study, published today in Scientific Reports, has found that machine learning has the potential to enhance and improve a veterinarian's ability to accurately diagnose herd mastitis origin and reduce mastitis levels on dairy farms.

Mastitis is an extremely costly endemic disease of dairy cattle, costing around £170 million in the UK. A crucial first step in the control of mastitis is identifying where mastitis causing pathogens originate; does the bacteria come from the cows' environment or is it contagiously spread through the milking parlour?

This diagnosis is usually performed by a veterinarian by analysing data from the dairy farm and is a cornerstone of the widely used Agriculture and Horticulture Development Board (AHDB) mastitis control plan, however this requires both time and specialist veterinary training.

Machine learning algorithms are widely used, from filtering spam emails and the suggestion of Netflix movies to the accurate classification of skin cancer. These algorithms approach diagnostic problems as a student doctor or veterinarian might; learning rules from data and applying them to new patients.

This study, which was led by veterinarian and researcher Robert Hyde from the School of Veterinary Medicine and Science at the University of Nottingham, aims to create an automated diagnostic support tool for the diagnosis of herd level mastitis origin, an essential first step of the AHDB mastitis control plan.

Mastitis data from 1,000 herds' was inputted for several three-month periods. Machine learning algorithms were used to classify herd mastitis origin and compared with expert diagnosis by a specialist vet.

The machine learning algorithms were able to achieve a classification accuracy of 98% for environmental vs contagious mastitis, and 78% accuracy was achieved for the classification of lactation vs dry period environmental mastitis when compared with expert veterinary diagnosis.

Dr Hyde said: "Mastitis is a huge problem for dairy farmers, both economically and in welfare terms. In our study we have shown that machine learning algorithms can accurately diagnose the origin of this condition on dairy farms. A diagnostic tool of this kind has great potential in the industry to tackle this condition and to assist veterinary clinicians in making a rapid diagnosis of mastitis origin at herd level in order to promptly implement control measures for an extremely damaging disease in terms of animal health, productivity, welfare and antimicrobial use."

In the 2020 February 25 issue of Scientific Reports, a research group from the Department of Hepatology in Osaka City University Graduate School of Medicine, Japan reported that levels of a circulating soluble immune checkpoint protein can be used as a potential marker to predict overall survival in patients with advanced HCC. In addition, treatment with an anti-angiogenic agent sorafenib, the current first-line systemic therapy, revealed dynamic changes of soluble checkpoint protein levels in patients with advanced HCC.

Immune checkpoint inhibitors, including monoclonal antibodies that target inhibitory immune receptors such as programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), have emerged as promising treatments for many types of cancer. However, immune checkpoint inhibitors have not been approved for treatment of un-resected, advanced HCC. Some anti-angiogenic agents including sorafenib are currently recommended as first-line or second-line treatments for patients with advanced HCC who have well-preserved liver function. Clinical trials that combine the use of an anti-angiogenic agent with an immune checkpoint inhibitor, such as bevacizumab plus atezolizumab, are ongoing.

This study profiled the baseline levels of 16 soluble checkpoint proteins and their changes following sorafenib treatment for HCC. Plasma samples were obtained from 53 patients with advanced HCC at baseline, week 1, 2 and 4 of sorafenib treatment, and tested for the concentrations of soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays. Multivariate analysis showed high soluble B- and T-lymphocyte attenuator (sBTLA) levels at baseline were an independent predictor of poor overall survival (Fig. 1). BTLA (indicated by arrows) was highly expressed in T cells and macrophages in peritumoral areas (Fig. 2). At week 2, the concentrations of most inhibitory proteins, including sBTLA, sLAG3, sCTLA-4, and sPD-1, had significantly increased (Fig. 3). The fold-changes of soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86, sPD-1 with sPD-L1; and the fold-changes of sCTLA-4 with sBTLA or sPD-1, were positively correlated (data not shown).

The preparation of molecular-targeted therapies is very costly, and therapeutic responses to treatment only occur in a minority of patients. Furthermore, reliable biomarkers that identify patients who would benefit from immunotherapy have yet to be identified. The research group will conduct further investigations in a large group of patients with HCC to explore potential biomarkers for predicting patient outcomes or therapeutic responses.

The design and rationale of the combinations of anti-angiogenic agents and immune checkpoint inhibitors were based on results of previous in vivo studies, indicating that anti-angiogenic agents might enhance anti-tumor immunity through multiple mechanisms. However, the immunomodulatory effects of anti-angiogenic agents in HCC had yet to be elucidated in a clinical setting. Associate Professor Masaru Enomoto said "it was quite surprising for us that even an anti-angiogenic agent alone resulted in the dynamic changes of the immune systems in patients with HCC. Further investigation is also necessary to determine which anti-angiogenic agents are optimal partners for specific immune checkpoint inhibitors, and how much the optimal doses are when used in combination."

PHOENIX, March 6, 2020 -- Large-scale analysis of electronic health record data from across the country reveals potential opportunities for improvement in how high blood pressure is managed, according to research presented today at the American Heart Association's Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2020. The EPI Scientific Sessions, March 3-6 in Phoenix, is a premier global exchange of the latest advances in population-based cardiovascular science for researchers and clinicians.

The study, along with a description of the Blood Pressure Control Laboratory (BP Control Lab) platform, is publishing simultaneously in the American Heart Association journal Circulation: Cardiovascular Quality and Outcomes.

Data from nearly 1.5 million eligible patients who completed 5.8 million clinic visits over one year, from 23 electronic health record datasets, found that 60% of patients had blood pressure controlled to below 140/90 mmHg. Readings above that level are considered too high and increase risk for heart attack and stroke.

In addition, only 12% of patients who had a high reading during a clinic visit received an order for a new class of blood pressure-lowering medication. The 2017 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommended adjusting blood pressure medications and/or doses when readings are high. When the best practice was followed, the average reduction in blood pressure was relatively large at 15 mmHg.

The researchers' analysis also found that only 22% of visits that had a high reading included a second reading to confirm the elevated blood pressure, as recommended by the guidelines.

"Our analysis of real world data from PCORnet indicates marked room for improving blood pressure control and blood pressure medication management for many patients," said Mark J. Pletcher, M.D., M.P.H., BP Control Lab principal investigator and professor of epidemiology and biostatistics at the University of California, San Francisco.

"We were particularly struck by the low rates of medication intensification when blood pressure is found to be high during a clinic visit - if we can improve medication prescribing rates, our data suggest we could make a big difference in blood pressure control," said Rhonda M. Cooper- DeHoff, Pharm.D., M.S., lead author of the abstract and associate professor in the College of Pharmacy at the University of Florida in Gainesville, Florida.

The BP Control Lab includes data from 23 health care organizations. The average age of patients in the system was 62 years; 10% were young adults (less than 45 years old); 18% were African American; 52% were female; 28% had diabetes; 15% had heart disease; and 14% had depression.

How individuals respond to government advice on preventing the spread of COVID-19 will be at least as important, if not more important, than government action, according to a new commentary from researchers at the University of Oxford and Imperial College London in the UK, and Utrecht University and the National Institute for Public Health and the Environment in the Netherlands.

As the UK moves into the "delay" phase of dealing with a possible COVID-19 epidemic, a new commentary, published today in The Lancet, looks at what we know so far about the new virus. The researchers, led by Professor Sir Roy Anderson at Imperial College and Professor Deirdre Hollingsworth at the University of Oxford's Big Data Institute, also suggest what can be done to minimise its spread and its impact.

Professor Hollingsworth said: 'Completely preventing infection and mortality is not possible, so this is about mitigation. Our knowledge and understanding of COVID-19 will change over time, as will the response. High quality data collection and analysis will form an essential part of the control effort. Government communication strategies to keep the public informed will be absolutely vital.'

Vaccine development is already underway, but it is likely to be at least a year before a vaccine can be mass-produced, even assuming all trials are successful. Social distancing is therefore the most important measure, with an individual's behaviour key. This includes early self-isolation and quarantine, seeking remote medical advice and not attending large gatherings or going to crowded places. The virus seems to largely affect older people and those with existing medical conditions, so targeted social distancing may be most effective.

Government actions will be important, including banning large events such as football matches, closing workplaces, schools and institutions where COVID-19 has been identified, and making sure that good diagnostic facilities and remotely accessed advice, like telephone helplines, are widely available. Ensuring the provision of specialist healthcare is also vital. The researchers warn, however, that large-scale measures may only be of limited effect without individual responsibility. All measures, of course, will have an economic impact, and some stricter measures, such as shutting down entire cities, as seen in Wuhan in China, may be less effective in Western democracies.

The aim of these social distancing measures is to "flatten the curve" of the infection, shown in the green trace in figure 1 (attached), slowing the spread and avoiding a huge peak in the number of new infections.

Flattening the curve can avoid overwhelming health services, keep the impact on the economy to within manageable levels and effectively buy more time to develop and manufacture effective vaccines, treatments and anti-viral drug therapies.

Sir Roy said: 'Government needs to decide on the main objectives of mitigation--is it minimising morbidity and associated mortality, avoiding an epidemic peak that overwhelms health-care services, keeping the effects on the economy within manageable levels, and flattening the epidemic curve to wait for vaccine development and manufacture on scale and antiviral drug therapies. We point out they cannot achieve all of these - so choices must be made.'

The researchers highlight that wider support for the health service and health care workers during an epidemic is vital in any case - during the Ebola epidemic in 2014-15, the death rate from other causes like malaria and childbirth rose sharply due to overwhelmed health services. The number of deaths indirectly caused by Ebola was higher than the number of deaths from Ebola itself.

While much has been made in the media of a number of "superspreading" events, where one infected individual has inadvertently spread the disease to many others, the authors warn that there are superspreading events in every epidemic, and care should be taken not to make too much of these.

Containing the spread of an infectious disease relies on keeping the "reproduction number", R0, the number of people infected by each infected person, below 1, when the pathogen will eventually die out. If R0 rises above 1, i.e. each infected person infects more than one other person, the pathogen will spread. Early data from China suggests that the R0 for COVID-19 could be as high as 2.5, implying that in an uncontained outbreak, 60% of the population could be infected. There are many unknowns in any new virus, however, and with COVID-19, it is not currently clear how long it takes for an infected person to become infectious to others, the duration of infectiousness, the fatality rate, and whether and for how long people are infectious before symptoms appear. It is also not currently clear if there are cases of COVID-19 which are non-symptomatic.

In comparisons with influenza-A (usual seasonal flu) and SARS, it currently seems likely that the epidemic will spread more slowly, but last longer, which has economic implications. Seasonal flu is generally limited by warmer weather, but as it is not known if this will affect COVID-19, the researchers say it will be important to monitor its spread in the Southern Hemisphere. Researchers will continue to collect and analyse data to monitor spread, while ongoing clinical research into treating seriously ill patients is also necessary.

One of the main priorities for researchers and policymakers will be contact tracing, with models suggesting that 70% of people an individual has come into contact with will need to be traced to control the early spread of the disease. The authors say other priorities include shortening the time from symptom onset to isolation, supporting home treatment and diagnosis, and developing strategies to deal with the economic consequences of extended absence from work.

Author Professor Hans Heesterbeek from the Department of Population Health Sciences at the University of Utrecht said: 'Social distancing measures are societally and economically disruptive and a balance has to be sought in how long they can be held in place. The models show that stopping measures after a few months could lead to a new peak later in the year. It would be good to investigate this further.'

A molecular marker in saliva is associated with the emergence of childhood obesity in a group of preschool-aged Hispanic children.

The intriguing discovery, reported in the journal BMC Medical Genetics, supports ongoing efforts to identify biomarkers associated with the emergence of childhood obesity before body mass index (BMI) is designated as obese, said Shari Barkin, MD, MSHS, director of Pediatric Obesity Research at Monroe Carell Jr. Children's Hospital at Vanderbilt.

"Understanding the factors that predispose children to obesity is important and will pave the way toward better prevention and early intervention," said Barkin, William K. Warren Foundation Professor of Medicine and chief of the Division of General Pediatrics.

The prevalence of pediatric obesity has been increasing at an alarming rate, Barkin noted, with a disproportionate burden in Hispanic populations. Pediatric obesity is associated with the onset of later comorbidities including Type 2 diabetes, high blood pressure and cancer.

"Right now, we only have crude markers to predict the emergence of obesity; we wait until the BMI is a certain number to intervene," Barkin said. "We're looking for markers that will allow us to intervene much earlier."

Barkin and her colleagues collected saliva samples at baseline from children who were enrolled in the Growing Right Onto Wellness (GROW) trial. A total of 610 parent-preschool child pairs, 90% of whom were Hispanic, received high-dose behavioral intervention during a three-year study period. At enrollment, the children were at-risk for obesity, but not yet obese.

"Even though many of the children in our intervention group compared to our control group improved their nutrition, maintained physical activity consistent with guidelines and got sufficient sleep, 30% of them still emerged into obesity," Barkin said. "This sheds new light on how we think about the interaction of behavior and genetics and how that might contribute to health disparities."

The investigators had collected saliva as an easily accessible, non-invasive tissue that they hoped would reveal genetic and epigenetic factors that might predispose a child to obesity.

In a previous study, they analyzed saliva samples from a subset of the enrolled children for methylation of genes associated with obesity. Methylation is an epigenetic "mark" on DNA that regulates gene expression. They found that methylation at 17 DNA sites in the child's baseline saliva was associated with the mother's BMI and waist circumference, suggesting that obesity risk may be transmitted from mother to child.

Now, they have evaluated associations between baseline salivary methylation and objective changes in child BMI after three years in the study.

"At baseline, these children were all non-obese, but based on their maternal BMI, their DNA was methylated differently at 17 sites," Barkin said. "Now we know that some of them emerged into obesity. We asked, 'Could we have predicted that from differences in methylation, even after accounting for maternal BMI and assessing other behavioral factors?'"

The answer looks like it is "yes." The investigators found that methylation of a gene called NRF1, which has roles in adipose tissue inflammation, was associated with childhood obesity. A child with the NRF1 methylation at baseline had a threefold increased odds of being obese three years later, after controlling for maternal BMI and other factors.

"This is a proof-of-principle study; it needs to be repeated with larger numbers of children," Barkin said. "But even with small numbers, we found a really important signal using salivary epigenetics."

The study demonstrates the utility of using saliva for epigenetic studies and points to at least one gene, NRF1, that should be more extensively studied for its role in the emergence of obesity.

"Most studies have looked for factors in children who are already obese," Barkin said. "Our study demonstrates that there are already changes in the physiology -- a pathway to obesity -- even before the phenotype of obesity emerges. If we can define a predictive epigenetic signature, we can intervene earlier to reduce health disparities in common conditions like obesity."

Over 30 percent of injury survivors who are treated in hospital emergency departments will have moderate-to-severe symptoms of posttraumatic stress disorder (PTSD) at some point in the first year following the initial incident, new research led by the Yale School of Public Health finds.

Assistant Professor Sarah Lowe, Ph.D., and colleagues pooled data from more than 3,000 people who were treated in emergency rooms in six countries: Australia, Israel, Japan, the Netherlands, Switzerland and the United States.

The study, published in the journal Psychological Medicine, examined PTSD symptoms over time and found that 64.5 percent of participants were resilient, exhibiting consistently low symptoms. The remaining 35.6 percent, however, fell into one of four other patterns, including initially high PTSD symptoms that decreased over time (16.9 percent), moderate symptoms (6.7 percent), delayed symptoms (5.5 percent) and chronically high symptoms (6.5 percent).

Factors associated with high PTSD symptoms were also identified in the study. Injuries that were due to physical assault, versus other causes, were shown to be especially predictive of immediate and longer-term symptoms over the first year. Survivors who had a history of interpersonal violence, including physical abuse and sexual assault, were also at greater risk.

Higher educational attainment was associated with fewer PTSD symptoms, the study found.

"By looking at PTSD symptom patterns across different contexts, we can have greater confidence in predicting which patients are likely to need short- and long-term mental health services," said Lowe, a member of the Department of Social and Behavioral Sciences. "Combining data from six countries was a major undertaking, but certainly worth the effort."

PTSD is characterized by a constellation of distressing symptoms, including nightmares, avoidance of reminders of the traumatic event, anger and irritability and an exaggerated startle response. The disorder is associated with increased risk for a variety of other negative consequences, including poor physical health, strained social relationships and disruptions in education and employment.

Lowe conducted the study with collaborators from the International Consortium to Predict PTSD, a large-scale effort to better understand the factors contributing to PTSD after a traumatic injury.

While the study is the first to examine PTSD symptom trajectories with pooled data, Lowe and colleagues hope that their work inspires researchers in other trauma exposed populations, including sexual assault and disaster survivors, to do the same.

The study was supported with a grant from the National Institutes of Health.

Tuberculosis is distinguished primarily by the persistent cough that serves to spread the disease. Stopping whatever triggers that cough could greatly reduce the transmission of the disease, which annually kills more than 1.3 million people worldwide.

Researchers from The University of Texas at Dallas' Center for Advanced Pain Studies worked with colleagues from UT Southwestern Medical Center to pinpoint a molecule that the tuberculosis bacterium manufactures to induce coughing.

Their findings, published online March 5 in the journal Cell, could help reduce the impact of tuberculosis, which remains one of the top 10 causes of death worldwide, according to the World Health Organization.

"Tuberculosis deaths have been greatly reduced in the United States, but it is still a huge issue in many parts of the world, and we would love to have an impact on stopping the spread of the disease," said Dr. Ted Price BS'97, Eugene McDermott Professor of neuroscience in the School of Behavioral and Brain Sciences (BBS) and one of five UT Dallas authors of the Cell paper. "Discovering the mechanism through which TB causes cough affords just such an opportunity, and our collective team has the appropriate expertise to tackle this problem, which we have started to accomplish through this work."

The idea that nociceptors -- the nerve cells that respond to pain stimuli -- cause the coughing associated with TB runs counter to existing suppositions that link the cough to infection-induced lung inflammation or irritation.

"No one had ever shown that TB produces an irritant that acts directly on the sensory innervation of the lungs," Price said. "We have now shown this directly through our collaborative work on this project."

In testing on rodents, researchers sought to identify the components or products of the Mycobacterium tuberculosis that cause coughing or trigger nociceptors. Ultimately, they identified a fatty acid called sulfolipid-1 (SL-1) as a pain-response trigger. They then reproduced that response in isolated human nociceptor cells. Finally, the researchers altered a strain of Mycobacterium tuberculosis to not produce SL-1. Rodents infected with this version developed other tuberculosis symptoms, but not coughing.

If researchers can show that suppressing cough does not worsen the condition of tuberculosis patients, the spread of the disease might be prevented by developing a drug that inhibits SL-1 production, Price said.

"People with active tuberculosis can cough for months and spread disease even when they are receiving appropriate treatment," said corresponding author Dr. Michael Shiloh, associate professor of internal medicine and microbiology at UT Southwestern. "Someday, doctors may give antibiotics in conjunction with a medication that prevents coughing, which in turn could prevent spread."

CHICAGO (March 6, 2020): Although papillary thyroid carcinoma is the most common form of thyroid malignancy, it is considered to be an indolent disease that progresses slowly and has an excellent prognosis. Patients, therefore, may be monitored on a regular basis rather than undergo a surgical procedure at the outset. But results from a new large-scale study show that in nearly 20 percent of patients, papillary thyroid tumors less than 1 cm in size had pathological signs of more aggressive disease that increased the risk that these patients might develop distant metastasis (spread of the disease to other areas of the body away from the primary site of cancer). The study demonstrates the need for developing sophisticated tests that will find patients with these pathological signs early on and for them to be counseled on all treatment options, including immediate surgical removal of part or all of the thyroid gland. The research study appears in an "article in press" on the Journal of the American College of Surgeons website in advance of print.

Thyroid carcinoma is the most common malignancy of the endocrine system, and the papillary form of the disease accounts for 70 to 90 percent of these malignancies. Papillary thyroid microcarcinoma (PTMC) is a specific subgroup of papillary thyroid carcinoma that accounts for 30 percent of all papillary thyroid malignancies.1,2

The prognosis for patients with PTMC is good; the disease is responsible for only 3 percent of all deaths from thyroid cancer and 5 percent of deaths of patients with papillary thyroid carcinoma.2 The indolent course of the disease is shown by the relatively high prevalence of PTMC in autopsies of individuals who died of other causes (3 to 36 percent) and comparable clinical outcomes for patients whether they underwent an operation or not.3 The American Thyroid Association's 2015 guidelines for treatment of PTMC support surgical removal of the thyroid gland of patients with PTMC. The guidelines also, however, discuss active surveillance or regular intensive monitoring and repeat testing, and at least one clinical trial recommended observation of patients with PTMC.4,5

Patients with suspected PTMC typically have preoperative ultrasound or biopsy. However, pathological features of aggressive disease can be found only on a full examination of tissue removed at the time of surgery.

"In general, PTMC tumors are not aggressive and not likely to affect overall survival. However, there are subsets within the patient population who may develop more serious cancers that could be life-threatening. With that in mind, we looked specifically at the risk of distant metastasis and the pathological profiles of patients with PTMC," said lead author of the study Zaid Al-Qurayshi, MD, MPH, department of otolaryngology-head and neck surgery, University of Iowa Hospitals and Clinics, Iowa City.

The researchers retrospectively analyzed 30,180 adult patient records in the National Cancer Database (NCDB) who were treated for PTMC between 2010 and 2014. NCDB is a joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Among these patients, 5,628 (18.7 percent) exhibited pathological signs of advanced disease, such as central lymph node metastasis (8 percent), lateral lymph node metastasis (4.4 percent), microscopic disease outside of the thyroid (6.7 percent), gross disease outside the gland (0.3 percent), invasion of the lymphatics and blood vessels (4.4 percent), and distant metastasis (.04 percent).

The presence of some of these pathological features was associated with spread of the disease or a lower survival rate. "The death rate for patients with disease in the lymph nodes was 3 times higher, and it was 6 times higher for those with distant metastasis or spread to the lungs," said Emad Kandil, MD, FACS, a study coauthor and a professor of surgery in the department of surgery, Tulane University School of Medicine, New Orleans, La.

"Having a lymph node metastasis triples the risk of having distant metastasis. Extrathyroidal extensive has a 5-fold risk of spreading to the lymph nodes and a 9-fold risk of distant metastasis. These factors are all connected," Dr. Kandil said.

"The study provides a good, general perspective about the landscape of PTMC. More granular, clinical data are needed to help understand the risk factors for advanced disease and develop a preoperative test that could identify these patients who have them," Dr. Al-Qurayshi said.

Dr. Kandil's laboratory is currently testing a panel of genes that may tell which cancers will progress and which will not. In the meantime, all patients with PTMC should be carefully counseled.

"We don't have enough information at this time to confirm how the disease may progress. However, we do need to let patients know about the possible presence of aggressive disease and all their options for treatment," Dr. Kandil concluded.

(Boston)-- While there is an association between liver fibrosis and heart failure, the mechanisms for this association are currently unclear but may be of particular importance for people living with human immunodeficiency virus (HIV) and/or hepatitis C, both of which are chronic infections that affect the liver and heart.

Prior research has shown that people with a certain type of liver disease that involves scarring of the liver (fibrosis) have a higher risk of heart failure. Now these same researchers have discovered that this higher risk may be specific to a certain kind of heart failure called heart failure with preserved ejection fraction (HFpEF).

A multidisciplinary team, led by a researcher from Boston University School of Medicine (BUSM) grouped U.S. Veterans from the Veterans Aging Cohort Study (VACS) who had never had heart failure into three categories representing advanced fibrosis, indeterminate fibrosis, and no advanced fibrosis. They then observed these individuals until they experienced new onset heart failure or death and then estimated the rates and risk of heart failure across the three liver fibrosis groups.

"Our findings suggest that the link between liver fibrosis and heart failure may be specific to one type of heart failure (preserved ejection) and not heart failure with reduced ejection fraction," explained corresponding author Kaku So-Armah, PhD, assistant professor of medicine at BUSM.

According to the researchers, implications of this work include the need for ongoing research focusing on the role of liver fibrosis in new onset heart failure, particularly HFpEF. Further implications include the need to screen for and reduce heart failure risk among people with liver disease, particularly among people with conditions like HIV or hepatitis C that enhance the overall risk of heart failure.

"People with advanced liver fibrosis, including people without HIV or hepatitis C, may have increased risk for heart failure with preserved ejection fraction compared to people without evidence of advanced liver fibrosis. Preventing liver fibrosis, particularly among people already at high risk for heart failure, may be an important factor in preventing or reducing risk of heart failure with preserved ejection fraction; an idea to be tested in future studies."

WEST LAFAYETTE, Ind. -- Our brains make our lives easier by predicting what will happen next based on previous experiences. But what happens when those predictive powers don't work like they should?

Autism spectrum disorder and other neurological disorders involve problems with brain prediction. For example, the brain usually remembers situations that can become dangerous - such as a hot stove or a car coming toward you while you're crossing the street. For someone with autism, the brain can't always predict those things.

A professor at Purdue University is discovering how complications with prediction lead to changes in sensory perception and learning impairments, both of which are common symptoms of autism.

"The brain precomputes everything," said Alexander Chubykin, assistant professor of biological sciences. "When you see something familiar, it immediately tries to remember what it is and that's how we know what will happen next. My lab is trying to understand how the brain distinguishes between something that is familiar and novel and how that plays into neurological disorders."

Through his research, Chubykin's goal is to work on developing new biomarkers to make diagnosing disorders such as autism easier and make advancements toward discovering potential new drugs for treatment.

Understanding how the brain predicts future events is critical when it comes to defining and understanding neurological disorders, Chubykin said. It's also a key to survival and normal brain function.

"If you see something dangerous, your brain usually recognizes that and predicts something bad could happen." Chubykin said. "If you have this previous experience and can process this information, you can escape in time. When your brain can't tell you those things, it's overwhelming and frightening."

Chubykin says understanding how the brain decides what it should pay attention to in the first place is key to understanding how prediction plays a role in disorders such as autism. In order for the brain to decide what is novel, it needs to first recognize a sensory stimulus. Recognition of the familiar stimulus leads to a generation of an expectation or prediction. However, when a prior expectation is violated, that leads to a surprise. These surprises are called prediction errors, which is when the senses do not correspond to the brain's predictions.

When the brain receives surprises, it then wants to minimize that surprise in the future by memorizing it and the corresponding environment, a process otherwise known as learning.

"We continually receive new sensory information, and we learn it," Chubykin said. "But for someone with a disorder such as autism, it's not that easy." In autism, the brain can't always accurately predict what will happen in the near future from senses such as vision, touch, and hearing.

That's why people affected by autism often experience "sensory overload," which is when sensory input overrides prediction. Sensory overload can cause stress and makes it difficult to focus.

"For instance, if I have an umbrella sitting in the corner of my office and I see it every day, my brain knows it's going to be there and it's not a surprise," Chubykin said. "I get used to it being there. But for patients with autism, it might take them a while to process it. It may also take them longer to get used to new environments with a lot of new sensory stimuli, and it's these details that overwhelm them."

Chubykin also led recently published research that revealed mice can perceive so-called Kanizsa optical illusions and the neural mechanisms that are involved. The work was published in the Journal of Neuroscience.

"Patients with autism and schizophrenia typically have difficulty perceiving this illusion," Chubykin said. "This could be significant for diagnostic testing of early detection of autism and schizophrenia in the future. The reason for that is that this illusion tests the ability to do spatial prediction."

He says in schizophrenia, prediction also is impaired, but it is the complete opposite of autism.

"For patients with schizophrenia, their brains have a higher emphasis on prediction compared to senses," Chubykin said. "When they're hallucinating or hearing voices, their internal predictions override their senses."

Chubykin wants his research to provide answers for both patients and their families. The earlier these disorders can be diagnosed, the quicker patients can get the help they need.

"The more we learn, the more we can help," Chubykin said.