Body

MADISON - Ten years ago, in Marathon County, Wisconsin, 55 people were sickened by an uncommon fungal infection called blastomycosis. Thirty patients were hospitalized. Two people died.

The fungus, Blastomyces dermatitidis, found naturally in wet soil and in decomposing wood throughout the Great Lakes region and the Mississippi Valley, can cause flu-like illness and in severe cases, death. Wisconsin has among the highest incidence rates of the disease in the U.S. and outbreaks ranging up to 100 cases periodically occur in the state.

Given the size of the Marathon County outbreak, the state asked the U.S. Centers for Disease Control and Prevention for help launching an investigation -- unusually, 20 patients infected with the fungus were of Hmong descent. Investigators found that Asian people had a disproportionate risk of developing blastomycosis infections relative to other groups in the U.S. and they ruled out lifestyle explanations, such as gardening practices and recreation.

Now, a new study led by University of Wisconsin-Madison researchers Caitlin Pepperell and Bruce Klein has identified a specific genetic vulnerability among Hmong people that renders them more susceptible to the disease-causing fungus.

"We were struck by this because it hadn't been described before ... rates were 10-to-100 times greater than one might expect based on population numbers alone," says Klein, an infectious disease physician and professor of pediatrics, internal medicine, and medical microbiology and immunology at the UW School of Medicine and Public Health (SMPH). "It's really been a holy grail question -- why are some people more vulnerable and what is the basis for this?"

Understanding these vulnerabilities is really important for patients, says Pepperell, also an infectious disease physician and associate professor of medicine and medical microbiology and immunology at SMPH, because it can help physicians make better-informed and more timely decisions about treatment for people who are at higher risk.

"Unfortunately, a really typical story with blastomycosis is having a long delay to diagnosis because it's a (relatively) rare disease and people are not familiar with it," Pepperell says. The earlier people are treated, the better their outcomes.

At the start of the study, recently published in the open-access journal mBio, Pepperell surmised that Hmong people in Wisconsin, who have "experienced a long series of forced displacements and migrations," might be more genetically isolated than other groups and thus have less genetic variation powering their fight against some diseases.

That's because every gene we inherit exists in pairs called alleles -- we get one copy from each parent. Having two alleles that are different creates variation, but as is often the case in genetically isolated groups, the alleles can also be identical, or homozygous. A person who inherits one good copy of a gene and one bad still has some protection from its effects, while a person who gets two bad copies is more vulnerable.

"Many disease-causing variants are homozygous," Pepperell explains.

With the help of her former graduate student, co-author Donny Xiong, the research team gained consent from nine of the affected Hmong patients to collect blood and examine their cells.

Pepperell and her graduate student, study co-author Mary O'Neill, looked for long stretches of homozygosity in the genomes of the Hmong participants. They found them in a region known to be important for immune responses to fungi.

Within that region are genes for an immune element known as cytokine interleukin-6 (IL-6), which helps lead to the development of another immune responder known as interleukin-17 (IL-17), involved in teaching the body to fight fungal infections. The research team found that the cells of Hmong people created less IL-6 than the cells of European donors.

The specialized cells that produce IL-17, called Type 17 cytokine T helper cells (TH17), "patrol the mucosal surfaces of the body and are important in alarming (the body's) first-line defenses," Klein explains. "They serve as the cavalry and mop up invaders."

Klein's research team found previously in mice that TH17 cells are particularly important for responding to fungal invaders and that IL-6 is pivotal to their creation. The finding suggested to the researchers that Hmong people who produce less IL-6 may have fewer TH17 cells, and thus, less IL-17.

So, Klein's team went back to the mouse model and found that mice lacking IL-6 had significantly fewer TH17 cells than normal mice, were extremely vulnerable to Blastomyces infection, experienced progressive disease, and died sooner.

The researchers also found that Hmong donor cells produced significantly less IL-17 than those from Europeans in response to infection with another more common fungus, Candida albicans. Both groups are more likely to have been exposed to this fungus before -- it's responsible for thrush and common vaginal yeast infections.

Klein and Pepperell continue to study genetic vulnerability to Blastomyces, which is part of a family of seven particularly pathogenic fungi that are harmless unless their spores are inhaled and take up residence in the lungs. Pepperell is interested in "zooming out" to see if other genes may be different in Hmong people, since this study looked specifically at immune-related genes and could be missing more of the big picture.

For Klein, the work has been "extremely gratifying." He has studied blastomycosis in Wisconsin since 1981, first as a trainee with the CDC's Epidemic Intelligence Service, and long worked alongside the late state epidemiologist, Jeff Davis, who passed away just last year. Together, they helped establish Wisconsin as the first state to make it a legally reportable infectious disease.

"It's like: 'Battle on,'" with this fungus," Klein says. He appreciates the implications the findings have not just for individual patients, but also for public health more broadly. It also helps lay the groundwork for the future, particularly as plans are forged by UW-Madison to establish the SMPH Center for Human Genomics and Precision Medicine.

"This is a great example of the Wisconsin Idea," Klein says. "This is something we should be doing -- the state and the university working together for the benefit of public health and people in Wisconsin."

Absorption heat transformers can effectively reuse the waste heat generated in various industries. In these devices, specialised liquids form thin films as they flow downward due to gravity. These liquid films can absorb vapour, and the heat is then extracted by a coolant so that it can be used in future processes. So far, however, there has been little research into how the performance of these films is influenced by the thermodiffusion effect - a behaviour seen in mixtures, where different types of mixture respond differently to the same temperature gradient. In a study recently published in EPJ E, researchers from the Fluid Mechanics group at Mondragon University and Tecnalia in Spain, led by M. M. Bou-Ali at Mondragon University, pooled their expertise in transport phenomena and absorption technology. Together, they explored for the first time the influence of the thermodiffusion property on the absorption, temperature and concentration profiles of falling films.

With the industrial sector currently producing vast amounts of waste heat, the study is part of a growing effort to increase its efficiency by recycling unused heat. The researchers discovered that when the mass transfer of different mixture components varies due to the thermodiffusion effect, as is seen in a liquid with a negative thermodiffusion coefficient (water-lithium bromide), the absorption of surrounding vapours can be increased. They also found that the absorption in the films changes significantly as they flow down, due to widely varying temperatures and concentrations. The team arrived at their conclusions by incorporating a variety of thermodiffusion effect equations into numerical models, and subsequently calculating the resulting degrees of vapour absorption in the films.

Since a third of our total energy consumption is currently in industrial processes, heat exchange devices are becoming more and more important to increasing their efficiency by recycling large amounts of heat. The work, therefore, offers valuable new insights into how the performance of falling film absorbers could be improved in the future.

Philadelphia, July 15, 2019 - Statins, the most commonly used effective lipid-lowering drugs, are significantly underutilized to treat lipid abnormalities in patients with and at risk for atherosclerotic cardiovascular disease (ASCVD), according to a retrospective study of more than 280,000 patients in Alberta, Canada. Investigators report in the Canadian Journal of Cardiology, published by Elsevier, that only two-thirds of these patients were receiving moderate/high-intensity statins, and of the ones treated, more than a third are under-treated based on the fact that they did not achieve recommended low-density lipoprotein cholesterol (LDL-C) levels at follow-up testing.

It should be noted that numerous studies have documented the benefits of appropriate statin use in at-risk populations, demonstrating reduction in atherosclerotic disease and the prevention of adverse outcomes like heart attacks, strokes, and deaths.

"Despite the known benefits of statins, a significant treatment gap persists in patients with ASCVD or at high risk of developing ASCVD. We need to conduct additional research to better understand contemporary management of these patients," said lead investigator Guanmin Chen, PhD, MD, MPH, Medlior Health Outcomes Research Ltd; Department of Community Health Sciences and Libin Cardiovascular Institute of Alberta; and O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Investigators assessed current patterns of lipid-lowering therapy for the management of LDL-C among 281,665 patients identified with ASCVD, based on administrative health system data for 2011-2015 from the province of Alberta. A retrospective study was conducted by linking multiple health system databases to examine clinical characteristics, treatments, and LDL. The objectives of the study were to characterize the proportion of patients with ASCVD and a statin prescription; to describe the intensity level of statins prescribed; and to determine the proportion of statin users who achieved recommended levels of LDL-C.

LDL-C was assessed at the first measurement (index test) and second measurement (follow-up test) during the study period. LDL-C levels were evaluated based on the 2016 Canadian Cardiovascular Society guideline recommendations for achieving less than 2.0 mmol/L or a 50 percent reduction. Statin therapies were categorized as low-, moderate-, and high-intensity.

Among the individuals identified with ASCVD during the study period, 78 percent had an index LDL-C test and 66 percent were prescribed lipid-lowering therapy. Most patients receiving any lipid-lowering therapy were on moderate-/high-intensity statins. Failure to achieve guideline-recommended levels of LDL-C was common among patients using moderate- or high-intensity statin therapy; and 40 percent of patients did not adhere to their treatment regimens.

"Given the remarkable treatment gap identified in these patients at-risk for ASCVD, the current study results may help to facilitate new strategies to reduce the number of untreated or under-treated patients," commented Dr. Chen. "Additional research is needed to assess the reasons for the observed treatment gaps and their effects on morbidity, mortality, and other important outcomes, such as health-related quality of life, functional status, as well as healthcare resource utilization and costs."

The authors recommend several strategies to help reduce this treatment gap: standardizing care through ASCVD-specific admission orders; implementing risk classification tools and corresponding statin treatment recommendations in lab orders; electronic medical record review; and a follow-up lipid profile at the time of discharge. US clinical guidelines have also recently highlighted new lipid-lowering therapies, including PCSK9 inhibitors, as an option for lipid management among very high risk ASCVD patients to lower risk of cardiovascular events.

"This study showed in a large contemporary Canadian population that statins are under-used to lower cholesterol. Increasing uptake of statins could drastically reduce the number of heart attacks, strokes, and death in patients with established vascular disease," explained co-investigator Todd Anderson, MD, Director, Libin Cardiovascular Institute; Professor & Head, Department of Cardiac Sciences; Professor in the Department of Medicine, Merck Chair, Cardiovascular Research, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada.

In an accompanying editorial, lead author Robert T. Sparrow, MD, Faculty of Medical Science, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, discusses the challenges of non-compliance, pointing out that statins are often the subject of negative news stories and internet postings that minimize their extremely well-established benefits and exaggerate their adverse effects to a degree not seen with other cardiovascular drugs. Therefore, patient education must often counter pre-existing biases introduced by the media.

"The results of this study bring to light an important principle: time and energy, not knowledge, are the real barriers to statin prescribing. The many health needs and perceptions of ASCVD patients, short appointments, and competing demands on physician time all combine to impede statin prescribing," commented Dr. Sparrow. "Reminder systems to identify undertreated patients and tools to streamline the treatment discussion process and encourage patient empowerment through education can lead to robust improvements. It is time to lighten the burden on physicians and encourage implementation of systems and programs around them to help improve their prescribing practices."

Low-density lipoprotein cholesterol (LDL-C) is sometimes called "bad" cholesterol because a high LDL level contributes to a build-up of plaque in the arteries, a condition called atherosclerosis. Measuring LDL-C in the blood is an important indicator in the development and management of ASCVD. The most commonly used medication to treat high LDL-C is a statin, which helps reduce LDL levels by interfering with cholesterol production in the liver.

What The Study Did: Blood samples taken over several years from cognitively normal study participants who developed Alzheimer disease were analyzed along with samples from individuals who did not develop the disease to evaluate whether there is an association between neuronal-enriched extracellular vesicle biomarkers (particles shed by all cells and found in blood) and Alzheimer disease.

Authors: Dimitrios Kapogiannis, M.D., of the National Institutes of Health in Baltimore is the corresponding author.

(doi:10.1001/jamaneurol.2019.2462)

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.

Babies whose mothers underwent surgery before pregnancy have an increased risk of opioid withdrawal symptoms at birth, according to a new study done by Dr. Nathalie Auger, researcher at the University of Montreal Hospital Research Centre (CRCHUM), and published in the Canadian Medical Association Journal : http://www.cmaj.ca/lookup/doi/10.1503/cmaj.181519.

"Use of opioids for pain control after surgery may increase the risk of opioid dependence in women and withdrawal in their newborns," said the study's lead author, Dr Auger, also a professor at the University of Montreal's School of Public Health.

"We found that mothers who had surgery before pregnancy had 1.6 times the risk of neonatal abstinence syndrome - that is, opioid withdrawal symptoms in their future newborns - perhaps because opioid use continues after surgery."

The large study included data on almost 2.2 million births in Quebec between 1989 and 2016. Of these, 2,346 newborns had neonatal abstinence syndrome, including 1,052 who had mothers who underwent prepregnancy surgery (14.9 per 10,000 babies) compared with 1,294 babies (8.8 per 10,000) born to mothers who did not have surgery.

Multiple surgeries, younger age at surgery, longer time between surgery and pregnancy, and cardiovascular, thoracic, urologic, or neurosurgery were associated with the largest risk of neonatal abstinence syndrome. There was also a strong association with general anesthesia, perhaps because this type of anesthesia is used in more complex surgeries, which can require longer use and higher dosage of pain relievers.

"Physicians have the potential to prevent neonatal abstinence syndrome with careful postoperative pain management in young women," Auger said. "Opioids continue to be overprescribed, despite calls to optimize postsurgical pain control through improvement of surgical guidelines and use of multipronged approaches with nonopioid painkillers or local anesthetics."

"Limiting postoperative opioid exposure, reducing overprescribing, and screening for opioid use in pregnant women who have had previous surgery may help reduce the risk of neonatal abstinence syndrome", she added.

It's marathon season, and every so often a news report will focus on an athlete who has collapsed from sudden cardiac arrest. Although uncommon, these events get attention. A new review in CMAJ (Canadian Medical Association Journal) looks at recent evidence to help physicians prevent and manage the risk of sudden cardiac arrest in competitive athletes.

Sudden cardiac arrest is rare and, in young athletes, is usually the first sign of heart disease, although one study found that 29% of athletes had symptoms of underlying disease before an arrest. It is very difficult to predict or prevent, and screening programs are challenging and of uncertain benefit. Physicians should routinely ask athletes if they feel dizzy, short of breath or experience chest pains during or after exercise and ask about family history to determine if there may be an inherited condition.

Survival rates after sudden cardiac arrest in athletes are quite high when automated external defibrillators are used.

"Establishing effective resuscitation protocols and increasing the availability of automated external defibrillators in settings where competitive sport is undertaken are the most effective strategies in helping reduce the incidence of sudden cardiac death among athletes," says Dr. Paul Dorian, a cardiologist at St. Michael's Hospital and the University of Toronto, Toronto, Ontario.

Visual abstract pre-embargo link: https://bit.ly/32fYNdl

Babies whose mothers underwent surgery before pregnancy had an increased risk of opioid withdrawal symptoms at birth, found a new study in CMAJ (Canadian Medical Association Journal).

"Use of opioids for pain control after surgery may increase the risk of opioid dependence in women and withdrawal in their newborns," says lead author Dr. Nathalie Auger, University of Montreal Hospital Research Centre, University of Montreal and McGill University. "We found mothers who had surgery before pregnancy had 1.6 times the risk of neonatal abstinence syndrome; that is, opioid withdrawal symptoms in their future newborns, perhaps because opioid use continues after surgery."

The large study included data on almost 2.2 million births in Quebec between 1989 and 2016. Of the total, 2346 newborns had neonatal abstinence syndrome and, of these, 1052 had mothers who underwent prepregnancy surgery (14.9 per 10 000 babies) compared with 1294 babies (8.8 per 10 000) born to mothers who did not have surgery. Multiple surgeries; younger age at surgery; longer time between surgery and pregnancy; and cardiovascular, thoracic, urologic, or neurosurgery were associated with the largest risk of neonatal abstinence syndrome. There was also a strong association with general anesthesia, perhaps because this type of anesthesia is used in more complex surgeries, which can require longer use and higher dosage of pain relievers.

"Physicians have the potential to prevent neonatal abstinence syndrome with careful postoperative pain management in young women," says Dr. Auger.

"Opioids continue to be overprescribed, despite calls to optimize postsurgical pain control through improvement of surgical guidelines and use of multipronged approaches with nonopioid painkillers or local anesthetics," she says.

Limiting postoperative opioid exposure, reducing overprescribing and screening for opioid use in pregnant women who have had previous surgery may help reduce the risk of neonatal abstinence syndrome.

PHILADELPHIA --Weight bias is a common form of prejudice against people who are viewed as having excess weight. Some individuals who struggle with weight may internalize the stigma directed toward them, blaming and devaluing themselves because of their weight. While it's known that weight "self-stigma" is associated with poor mental and physical health, it isn't clear who is most prone to this internalization. In a new study published today in Obesity Science and Practice, researchers at Penn Medicine and the University of Connecticut Rudd Center for Food Policy and Obesity surveyed more than 18,000 adults enrolled in the commercial weight management program WW International (formerly Weight Watchers Inc.), and found that participants who internalized weight bias the most tended to be younger, female, have a higher body mass index (BMI), and have an earlier onset of their weight struggle. Participants who were black or had a romantic partner had lower levels of internalization.

"We don't yet know why some people who struggle with their weight internalize society's stigma and others do not," said the study's lead author Rebecca Pearl, PhD, an assistant professor of Psychology in Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. "These findings represent a first step toward helping us identify, among people trying to manage their weight, who may be most likely to self-stigmatize. People who are trying to lose weight may be among the most vulnerable to weight self-stigma, but this issue is rarely discussed in treatment settings."

Research has found that, beyond the effects of BMI and depression, self-directed weight stigma is associated with increased risk for cardiovascular and metabolic disease. In this study--the largest investigation of weight self-stigma in the world--researchers surveyed adults to identify key characteristics and experiences of people who internalize weight bias.

Participants recalled when in their life they experienced weight stigma from other people, how frequent and how upsetting the experiences were, and who it was that called them names, rejected them, or denied them an opportunity simply because of their weight. Results showed that almost two-thirds of the participants reported experiencing weight stigma at least once in their life, and almost half reported experiencing these events when they were children or teens. The researchers examined the relationships between these experiences and levels of self-directed stigma.

Participants who reported experiencing weight stigma from others had higher levels of internalized weight bias than those who reported no experiences of weight stigma. Researchers say this was particularly true for participants who had weight-stigmatizing experiences early in life and continued to have these upsetting experiences as adults. People who experienced weight stigma from family members or friends, or from those in their workplace, community, or health care setting, also had greater evidence of weight self-stigma compared to participants who did not encounter weight stigma from those sources.

"Our findings can inform ways to support people who are experiencing or internalizing weight stigma, including opportunities to address weight stigma as part of weight management and healthy lifestyle programs," said the study's principal investigator Rebecca Puhl, PhD, a professor of Human Development and Family Sciences at the University of Connecticut.

The study sample, although the largest to date, represented only a small percentage of WW members, so the findings may not generalize to all members or to adults trying to lose weight in other ways. Some prior research has suggested that people who internalize weight bias may have worse long-term weight loss outcomes, but more research on this topic is needed.

In addition, Pearl's team is developing a psychological intervention for weight self-stigma that can be incorporated into weight management.

Young athletes who do not achieve a 90 percent score on a battery of tests that measure fitness to return to athletic competition, including quadricep strength, are at increased risk for a second knee injury, according to research presented at the Annual Meeting of the American Orthopedic Society of Sports Medicine.

Orthopedic surgeons and sports medicine professionals have established return-to-sports criteria to help guide patients as they consider participating in athletic competition after injury. Researchers pointed to the strength of the quadricep as one of the most important measures to predict risk for further injury to the anterior cruciate ligament.

Researcher Dr. Mark V. Paterno, Division of Sports Medicine, Cincinnati Children's Hospital, Cincinnati, and fellow researchers followed 181 patients, average age 16 years old, for two years.

Each patient was given a return-to-sport assessment that included six tests: isometric quadriceps strength, four functional hop tests and the International Knee Documentation Committee (IKDC) patient reported outcome survey. Limb symmetry index was calculated for strength and hop test assessments. Subjects were classified as patients who successfully passed all six return-to-sport tests at a level of 90 compared to those that failed to meet all six criteria.

The researchers sought to determine if successfully passing all six measures resulted in a reduced risk of second ACL injury in the first 24 months after returning to their sport, as well as to assess if ability to successfully pass individual return-to-sport criteria resulted in reduced risk of a second ACL injury.

Of the 181 patients enrolled, 39 suffered a second ACL injury with 18 ipsilateral graft failures and 21 contralateral ACL tears in the first 24 months after RTS following surgery. At the time of return-to-sport assessment, 57 patients achieved 90 percent or greater on all testing.

When individual return-to-sport criterion were evaluated, patients who failed to achieve 90 percent quadricep strength were 84 percent less likely to suffer an ipsilateral graft failure but three times more likely to suffer a contralateral ACL injury.

The doctors reported that current criteria to evaluate readiness to return young athletes to pivoting and cutting sports may not identify young, active patients independently at high risk for a future ipsilateral graft tear or contralateral ACL injury.

"Further investigation is needed on the relationship between quad strength and side of future ACL injury and whether other factors may help contribute to a predictive model of future ACL injury specific to limb," said Paterno.

Vast rings of electrically charged particles encircle the Earth and other planets. Now, a team of scientists has completed research into waves that travel through this magnetic, electrically charged environment, known as the magnetosphere, deepening understanding of the region and its interaction with our own planet, and opening up new ways to study other planets across the galaxy.

The scientists, led by Eun-Hwa Kim, physicist at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL), examined a type of wave that travels through the magnetosphere. These waves, called electromagnetic ion cyclotron (EMIC) waves, reveal the temperature and the density of the plasma particles within the magnetosphere, among other qualities.

"Waves are a kind of signal from the plasma," said Kim, lead author of a paper that reported the findings in JGR Space Physics. "Therefore, the EMIC waves can be used as diagnostic tools to reveal some of the plasma's characteristics."

Kim and researchers from Andrews University in Michigan and Kyung Hee University in South Korea focused their research on mode conversion, the way in which some EMIC waves form. During this process, other waves that compress along the direction they travel from outer space collide with Earth's magnetosphere and trigger the formation of EMIC waves, which then zoom off at a particular angle and polarization -- the direction in which all of the light waves are vibrating.

Using PPPL computers, the scientists performed simulations showing that these mode-converted EMIC waves can propagate through the magnetosphere along magnetic field lines at a normal angle that is less than 90 degrees, in relation to the border of the region with space. Knowing such characteristics enables physicists to identify EMIC waves and gather information about the magnetosphere with limited initial information.

A better understanding of the magnetosphere could provide detailed information about how Earth and other planets interact with their space environment. For instance, the waves could allow scientists to determine the density of elements like helium and oxygen in the magnetosphere, as well as learn more about the flow of charged particles from the sun that produces the aurora borealis.

Moreover, engineers employ waves similar to EMIC waves to aid the heating of plasma in doughnut-shaped magnetic fusion devices known as tokamaks. So, studying the behavior of the waves in the magnetosphere could deepen insight into the creation of fusion energy, which takes place when plasma particles collide to form heavier particles. Scientists around the world seek to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

Knowledge of EMIC waves could thus provide wide-ranging benefits. "We are really eager to understand the magnetosphere and how it mediates the effect that space weather has on our planet," said Kim. "Being able to use EMIC waves as diagnostics would be very helpful."

A new method of evaluating irregular heartbeats outperformed the approach that's currently used widely in stroke units to detect instances of atrial fibrillation.

The technology, called electrocardiomatrix, goes further than standard cardiac telemetry by examining large amounts of telemetry data in a way that's so detailed it's impractical for individual clinicians to attempt.

Co-inventor Jimo Borjigin, Ph.D., recently published the latest results from her electrocardiomatrix technology in Stroke. Among stroke patients with usable data (260 of 265), electrocardiomatrix was highly accurate in identifying those with Afib.

"We validated the use of our technology in a clinical setting, finding the electrocardiomatrix was an accurate method to determine whether a stroke survivor had an Afib," says Borjigin, an associate professor of neurology and molecular and integrative physiology at Michigan Medicine.

A crucial metric

After a stroke, neurologists are tasked with identifying which risk factors may have contributed in order to do everything possible to prevent another event.

That makes detecting irregular heartbeat an urgent concern for these patients, explains first author Devin Brown, M.D., professor of neurology and a stroke neurologist at Michigan Medicine.

"Atrial fibrillation is a very important and modifiable risk factor for stroke," Brown says.

Importantly, the electrocardiomatrix identification method was highly accurate for the 212 patients who did not have a history of Afib, Borjigin says. She says this group is most clinically relevant, because of the importance of determining whether stroke patients have previously undetected Afib.

When a patient has Afib, their irregular heartbeat can lead to blood collecting in their heart, which can form a stroke-causing clot. Many different blood thinners are on the market today, making it easier for clinicians to get their patients on an anticoagulant they'll take as directed.

The most important part is determining Afib's presence in the first place.

Much-needed improvement

Brown says challenges persist in detecting intermittent Afib during stroke hospitalization.

"More accurate identification of Afib should translate into more strokes prevented," she says.

Once hospitalized in the stroke unit, patients are typically placed on continuous heart rhythm monitoring. Stroke neurologists want to detect possible intermittent Afib that initial monitoring like an electrocardiogram, or ECG, would have missed.

Because a physician can't reasonably review every single heartbeat, current monitoring technology flags heart rates that are too high, Brown says. The neurologist then reviews these flagged events, which researchers say could lead to some missed Afib occurrences, or false positives in patients with different heart rhythm issues.

In contrast, Borjigin's electrocardiomatrix converts two-dimensional signals from the ECG into a three-dimensional heatmap that allows for rapid inspection of all collected heartbeats. Borjigin says this method permits fast, accurate and intuitive detection of cardiac arrhythmias. It also minimizes false positive as well as false negative detection of arrhythmias.

"We originally noted five false positives and five false negatives in the study," Borjigin says, "but expert review actually found the electrocardiomatrix was correct instead of the clinical documentation we were comparing it to."

More applications

The Borjigin lab also recently demonstrated the usefulness of the electrocardiomatrix to differentiate between Afib and atrial flutter. In addition, the lab has shown the ability of electrocardiomatrix to capture reduced heart-rate variability in critical care patients.

Borjigin says she envisions electrocardiomatrix technology will one day be used to assist the detection of all cardiac arrhythmias online or offline and side-by-side with the use of ECG.

"I believe that sooner or later, electrocardiomatrix will be used in clinical practice to benefit patients," she says.

A new study finds that trends in colonoscopy rates did not fully align with the increase in colorectal cancer (CRC) in younger adults, adding to evidence that the rise in early onset CRC is not solely a result of more detection. The study is published early online in the Journal of Medical Screening.

CRC incidence rates are declining rapidly in adults older than 55 years in the US, partly because of the widespread uptake of colonoscopy, which can remove precancerous growths, lowering incidence rates. In contrast, CRC incidence in younger adults is rising.

There remains debate whether the rise in incidence in younger adults reflects an actual increase in disease, or rather increased detection as a result of more colonoscopies being performed over time.

To add clarity to this debate, American Cancer Society researchers led by Stacey Fedewa, Ph.D. determined past-year colonoscopy rates among more than 50,000 respondents ages 40-54 in the National Health Interview Survey data. Colorectal cancer incidence rates and incidence rate ratios were calculated based on 18 population-based Surveillance Epidemiology and End Results registries during the same period.

Between 2000 and 2015, past-year colonoscopy rates were fairly stable among people aged 40-44 (remaining under 3%), while colorectal cancer incidence rates increased by 28%. Among those ages 45-49, colonoscopy rates doubled (from 2.5% in 2000 to 5.2% in 2015), while colorectal cancer incidence rates increased by 15%. In those ages 50-54, colonoscopy rates increased by about 2.5 times (from 5.0% to 14.1%), while incidence rates rose 17%.

If the growing incidence of young onset CRCs were a result of more detection, larger increases in early-stage diagnoses would be anticipated because screening is most likely to detect localized disease. To investigate this, researchers examined stage-specific CRC incidence trends from 2000-2015. Increases for localized stage disease occurred in ages 40-44, among whom colonoscopy was stable, but not in ages 45-49, among whom colonoscopy had increased. However, distant stage disease increased in every age group, and was steeper (2.9% per year) than that for localized stage (1.1% per year) in ages 40-44 years.

"The changes in past-year colonoscopy rates did not fully align with the rise in overall and distant stage colorectal cancer incidence rates in all three age groups during the corresponding period," said Dr. Fedewa. "There were some concordant patterns, like the rise in both colonoscopy and early stage incidence among 50-54 years, but there were also some discordant patterns, such as the lack of increase in colonoscopy among people in their early 40's to match the increasing rates of CRC in this age group."

"Future studies should examine reasons for the rising CRC incidence rates in young adults," the study concludes.

Finding a new doctor for health checkups and general care can pose a challenge to anyone. But for people who take prescription opioid pills for their chronic pain, it might be far harder, according to a new study.

In fact, 40% of 194 primary care clinics contacted for the study said they wouldn't accept a new patient who takes Percocet daily for pain from a past injury, no matter what kind of health insurance they had.

Another 17% of the clinics said they would want more information before deciding whether to take the patient; two-thirds of these said they would want the patient to come for a preliminary appointment before making a decision. All the clinics in the study were accepting new patients at the time.

The findings, published in JAMA Network Open by a team from the University of Michigan, suggest that more patients who take opioids for chronic pain face could health care access problems than previous studies have suggested.

However, the team did find that larger clinics and those that offer safety-net coverage were three times more likely than others to accept patients who currently take opioids for chronic pain.

More than just pain care

For such patients, getting access to primary care goes beyond checkups, preventive care and management of medical conditions, says lead researcher Pooja Lagisetty, M.D., M.Sc.

Having a regular provider could enable them to receive other pain-relieving treatments, and if indicated, provide guidance in safely and gradually tapering their use of opioids.

Primary care providers can also equip patients who take opioids, or their loved ones, with a "rescue" drug to use in case of an opioid overdose, screen patients for signs of opioid use disorders, and treat such disorders if the patient is among the minority of people on long-term prescription opioid treatment who develop an addiction to the drugs.

Without access to such care, the researchers note, patients may turn to other means of obtaining opioids, outside of a prescription from a regular provider. It also may lead to worsened health outcomes for their other medical issues like their diabetes or high blood pressure.

In fact, Lagisetty says, that's what led her and her colleagues to launch the study with funding from the Michigan Health Endowment Fund. Lagisetty is a general internal medicine physician at Michigan Medicine, U-M's academic medical center, and the VA Ann Arbor Healthcare System.

"Anecdotally, we were hearing about patients with chronic pain becoming 'pain refugees', being abruptly tapered from their opioids or having their current physician stop refilling their prescription, leaving them to search for pain relief elsewhere," she says. "However, there have been no studies to quantify the extent of the problem. These findings are concerning because it demonstrates just how difficult it may be for a patient with chronic pain searching for a primary care physician."

Calling around for care

The team did the study using a "secret shopper" method, to get a realistic sense of what clinics would tell someone who called to inquire about whether her parent could get an appointment as a new patient. The first round of calls went to 667 randomly chosen Michigan clinics, to ask if they were accepting new primary care patients and other questions.

For the second round of calls, the researchers used the scenario of an adult child calling on behalf of a parent, so that the conversations did not need to include detailed information about the patient for the purposes of scheduling an appointment.

The callers also said that their "parent" was taking medications for high blood pressure and high cholesterol, two conditions that primary care providers play key roles in managing.

The researchers wanted to find out if type of insurance, size or type of clinic, or population density around the clinic played any role. Half of the callers said their parent had Medicaid, the other half said they had Blue Cross Blue Shield coverage. Nearly half the clinics were in rural areas, and nearly one-third had a single provider. Nine percent were community health centers, which provide care to anyone regardless of ability to pay.

"Our results did not differ by insurance status, which was surprising because previous studies on primary care access have showed that patients on Medicaid tend to have lower access to primary care than those with private insurance," says Lagisetty. "This may indicate that providers and clinics are not making these decisions to restrict access based upon reimbursement. Larger clinics and community health centers were more likely to accept new patients suggesting that they may be some system level factors that affect access to care."

There was no difference in access between rural and urban areas.

Getting help for addiction issues

The researchers also looked at the availability of treatment for opioid use disorder at the primary care clinics.

Such treatment, which requires providers to get special training and permission from the federal government, involves counseling and prescriptions for medications that can block the symptoms of withdrawing from opioids. Lagisetty has looked at the feasibility of primary care clinics offering such treatment, and differences in access to it.

The front-line staff at 12% of the clinics in the study said their providers offered this kind of medication-based OUD care. Nearly 41% told callers they didn't know if their providers were able to offer it.

Next steps

What factors play a role in a clinic's decision to take on new patients with chronic pain who take prescription opioids? Lagisetty notes that patient advocates have placed blame on a 2016 chronic pain treatment guide from the Centers for Disease Control and Prevention, which they see as swinging the pain-treatment pendulum too far away from prescription opioids.

"I suspect this is only a small part of the problem," says Lagisetty, who is a member of the U-M Institute for Healthcare Policy and Innovation. "States, including Michigan, have implemented many other policies that are only occasionally based on the guidelines, in an effort to restrict opioid prescribing."

The Michigan team wants to study the factors responsible for this phenomenon further, and determine how much is related to recent guidelines and policies, how much is stigma against patients on opioid therapy, and how much is provider fear of legal repercussions.

"We hope to use this information to identify a way for us to fix the policies to have a more patient-centered approach to pain management," says Lagisetty. "Everyone deserves equitable access to health care, irrespective of their medical conditions or what medications they may be taking."

Washington, DC - July 12, 2019 - Surgical gowns and stainless steel remained contaminated with the pathogen Clostridium difficile even after being treated with the recommended disinfectant. The research is published July 12 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

"The spores of the bacteria were able to grow after decontamination," said principal investigator Tina Joshi, BSci, PhD, Lecturer in Molecular Microbiology, University of Plymouth, UK. "This shows that spores are becoming resistant and we need to reconsider how we decontaminate and employ hygiene measures in hospitals."

C. difficile infects roughly half a million Americans annually, killing 29,000. New strains are responsible for hard-to-treat cases of severe illness. Symptoms can range from diarrhea to fever, rapid heartbeat, inflammation of the intestines, and kidney failure. This pathogen commonly affects older adults in hospitals and in long-term care facilities.

The motivation for the research was a case in an American hospital in which gowns were suspected of contributing to transmission of C. difficile, said Dr. Joshi. The gowns were found to be contaminated with the deadly 027 strain of C. difficile.

The researchers examined the ability of C. difficile to adhere to, and subsequently transfer from hospital surgical gowns, by applying spores in sterilized water, at a concentration of 1 million per ml, directly to the surgical gowns in liquid for 10 seconds, 30 seconds, 1 minute, 5 minutes, and 10 minutes before being removed and discarded.. That methodology was designed to mimic transfer of infectious bodily fluids in the clinical setting in order to assess the potential for transmission to patients.

The numbers of spores recovered from gowns did not increase with contact time, suggesting that the spore transfer between surfaces occurred within the first 10 seconds of contact, said Dr. Joshi.

The single use gowns are... ineffective at trapping spores within their fibers and preventing the onward transmission of spores as demonstrated by spore recovery from the gowns, according to the investigators. This highlights the importance of ensuring that single-use surgical isolation gowns are used appropriately in infection prevention and control; i.e. [that personnel don the gowns upon entering and dispose of them when] exiting a single room to prevent spore transmission and incidence of [C. difficile infection].

The gowns were ultimately treated with disinfectant containing 1,000 ppm chlorine for 10 minutes. The disinfectant failed to clear the gowns of C. difficile. That "showed that the gowns can pick up and retain the spores," said Dr. Joshi. The spores on stainless steel and vinyl flooring also remained viable after treatment with the disinfectant.

"Due to this resistance, it may be prudent to reconsider how much biocide we use currently, and to ensure infection control is standardized. This work can be applied to hospitals anywhere in the world, and should help inform future guidelines on infection control and biocides," said Dr. Joshi.

A review addressing the challenges of testing for Clostridioides (Clostridium) difficile infection (CDI) and recommendations for newer diagnostic tests was recently published in Clinical Microbiology Reviews, a journal of ASM.

CLEMSON, South Carolina - Researchers from Clemson University's Environmental Toxicology Program have published research connecting an enzyme associated with detoxification to obesity and fatty liver disease, especially in males.

William Baldwin, professor and graduate program coordinator in the College of Science's department of biological sciences, and members of his laboratory used a novel mouse model developed in their laboratory to study the role of the Cyp2b gene in obesity. Cyp2b is a key enzyme involved in metabolism, particularly in the detoxification of chemicals in the body. Among other results, the research indicates a role for Cyp2b in unsaturated fatty acid metabolism, regardless of diet. Certain chemicals could inhibit Cyp2b, a phenomenon modeled by Cyp2b-null mice.

The study titled "Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis" was published in the Journal of Nutritional Biochemistry. It is part of a three-year, $362,000 grant Baldwin received from the National Institutes of Health to continue studies on how exposure to chemicals is likely to inhibit our bodies' internal mechanisms. Contributing to the paper were Melissa Heintz, Ramiya Kumar, Meredith Rutledge and Baldwin.

"The male Cyp2b-null mice are obese - and much more obese - than the wild-type mice that are also fed a high fat diet," Baldwin said.

There are several possible implications to human health.

"If you are exposed to chemicals that are metabolized by Cyp2b or inhibitors of Cyp2b, this might mean that you are not metabolizing something else in the body that is important," Baldwin said. "In turn, maybe your likelihood of retaining white adipose tissue increases and therefore your likelihood of being obese increases."

In addition, male Cyp2b-null mice had increased fatty liver disease without being fed a high-fat diet.

"Cyp2b must be signaling something and telling the fat to go someplace, indicating that Cyp2b has dual roles: metabolizing toxicants and chemicals in the environment and pharmaceuticals, but it is also involved in metabolism of lipids and probably involved in signaling to tell us how to distribute fat," Baldwin said.

With 40 percent of adults and 18.5 percent of youth in the United States now considered obese, the discovery that enzymes associated with detoxification may play a role in obesity - beyond the compounding effects of diet, exercise and general genetics - is critical.

Female Cyp2b-null mice did not show any greater propensity toward obesity, though there were indications that they have a higher rate of liver damage than wild-type female mice.

Gene expression was also affected. Cyp2b-null mice fed a normal diet have gene expression profiles similar to wild-type mice fed a high-fat diet.

"When the Cyp2b-null mice are fed a regular diet, their livers are acting like they are being fed a high fat diet," Baldwin said.

Heintz, a third-year Ph.D. candidate in environmental toxicology, said there are still many pathways to explore in this area of research.

"You might be healthy but you might be exposing yourself to a chemical in the workplace," she said. "Even though your diet is pretty good, if you are losing this activity of an enzyme in your liver, what you may not have thought would be important may be important in metabolizing fat."

This discovery also opens the door to exploring other enzymes that are currently thought to have one role but may also metabolize fat.

"Very little work has been done on this one particular enzyme, Cyp2b, and looking at its role in fatty acid metabolism," Heintz said. "It's just one gene and there could be more that do similar things."

"For all the obesity that occurred, the relative levels of fatty liver disease were not as high as we expected," Baldwin added. "We did the study for only 10 weeks, and if we want to study liver disease, we need to go further. We need to study the fatty liver disease phenomenon because that is the problem: 25 percent of the world's population has nonalcoholic fatty liver disease. That's increasing quite a bit."

Kumar earned a Ph.D. at Clemson and is now a senior clinical process associate with a clinical research company in Bangalore, India. Kumar said future research will show whether chemical inhibitors of these genes, such as plasticizers and pesticides, could also elicit a similar change in metabolism and lead to obesity.

"It will help us to plan better treatment regimens for obesity, along with changes in lifestyle and diet," Kumar said.

This research has the potential to inform how scientists look at a host of metabolic disorders and chronic conditions, all with the goal of increasing human health.

"I think it tells us that obesity - and potentially fatty liver disease - is a multi-component disease," Baldwin said. "It is about, first and foremost, eating the wrong foods or eating too much. But we can make it worse by external factors - whether that's chemicals, a lack of exercise or the components of our diets. There are a lot of little pieces to that, and this is one study that indicates that a healthy lifestyle involves a healthy diet, having the right calories and potentially avoiding some chemicals as well."