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CHICAGO --- Total deaths from heart disease, stroke, diabetes and hypertension - known collectively as cardiometabolic disease - have been increasing since 2011, a new Northwestern Medicine study shows. Cardiometabolic disease is the leading cause of preventable death worldwide.

While the overall rate of heart disease deaths decreased over time, the rate of decline slowed after 2010, the study found. Deaths from stroke and diabetes declined from 1999 to 2010 but leveled off after that. Deaths from high blood pressure increased between 1999 and 2017. Cardiometabolic death rates for black Americans remain higher than those for white Americans, the study found.

The findings will be published Aug. 27 in JAMA. Reporters can receive a copy of the paper by emailing mediarelations@jamanetwork.org.

"We know the majority of deaths attributable to cardiometabolic disease are preventable," said senior author Dr. Sadiya Khan, assistant professor of cardiology and epidemiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine cardiologist. "Our findings make it clear that we are losing ground in the battle against cardiovascular disease. We need to shift our focus as a nation toward prevention to achieve our goal of living longer, healthier and free of cardiovascular disease."

Until 2011, advancements in the diagnosis and medical and surgical treatment of cardiovascular disease had led to significant declines in deaths related to heart disease, stroke, diabetes and high blood pressure Khan said. Since then, however, age-adjusted mortality rates due to heart disease, stroke and diabetes have flattened, and death rates due to hypertension are increasing.

The scientists examined data from all United States deaths between 1999 and 2017 from the Centers for Disease Control's Wide-Ranging Online Database for Epidemiological Research (WONDER), with a specific focus on deaths caused by heart disease, stroke, diabetes and hypertension. They adjusted for age to account for different ages in the population.

The culprit, Khan said, may be the rise in obesity in recent decades. Although this dataset did not allow for identification of the causes of the worsening cardiometabolic disease trends, the prevalence of obesity has risen significantly since 2011, and obesity is a major risk factor for heart disease, Khan said.

"Cornerstones of good cardiometabolic health include maintaining a normal body weight, eating a healthful diet, staying physically active and not smoking," said first author Dr. Nilay Shah, a cardiology fellow at Feinberg and Northwestern Medicine. "These actions are important to preventing heart disease, no matter your age."

It is critical that prevention and management of risk factors for cardiometabolic health begins early in life, Khan said. This means consulting your doctor to assess your risk factors and engaging in heart-healthy behaviors.

Additionally, Khan said policy makers need to develop public health prevention strategies to support Americans in eating a healthy diet and having safe places to exercise in their neighborhoods, and increasing Americans' access to affordable health care and medications to equitably improve cardiovascular health on the population level.

Carrying ten kilograms of excess body fat increases the risk of depression by seventeen per cent. The more fat, the greater the probability of developing depression. This is the main conclusion of a new study carried out by researchers from Aarhus University and Aarhus University Hospital, Denmark.

"Our study also indicated that the location of the fat on the body makes no difference to the risk of depression. This suggests that it is the psychological consequences of being overweight or obese which lead to the increased risk of depression, and not the direct biological effect of the fat. If the opposite was true we would have seen that fat located centrally on the body increased the risk the most, as it has the most damaging effect in biological terms," says the study's last author Dr. Søren Dinesen Østergaard.

He is professor at the Department of Clinical Medicine at Aarhus University and affiliated with the Department of Affective Disorders at Aarhus University Hospital.

Prior studies in the field have predominantly used Body Mass Index (BMI) to measure obesity. BMI is calculated solely on the basis of body weight and height and is therefore a fairly crude measure, that does not, for example, take build and muscle mass into account.

"BMI is an inaccurate way of measuring overweight and obesity. Many elite athletes with a large muscle mass and a low body fat mass will have a BMI above 25, which is classified as overweight according to the common definition. This obviously doesn't make much sense. Therefore, one of the strengths of our study is that we've been able to zoom in and look at the specific relationship between the amount of body fat and the risk of depression," explains Dr. Østergaard.

In the study, which has been published in the journal Translational Psychiatry, the researchers have analysed data from two large genetic data sets: the UK Biobank, which contains data on the correlation between genetic variants and physical measurements (including body fat mass distributed around parts of the body); and the Psychiatric Genomics Consortium, which contains information on the correlation between genetic variants and depression.

Dr. Østergaard also highlights his research group's choice of the 'Mendelian randomization' method as the main reason why the study was successful. He also emphasises that the findings are particularly significant in light of the fact that almost 40 per cent of the world's adult population is overweight.

"In addition to the known physical consequences of obesity such as diabetes and cardiovascular disease, there is also a significant and now well-documented psychological component, which needs to be dealt with as well. This is yet another argument for resolving the obesity epidemic," he says, before emphasising that it is important to have a balanced approach to the issue:

"As it appears to be the psychological consequences of obesity, such as a negative body image and low self-esteem that is the main driving force behind the increased risk of depression, society's efforts to combat obesity must not stigmatise, as this will probably increase the risk of depression even further. It is important to bear this in mind so we can avoid doing more harm than good in the effort to curb the obesity epidemic," says Dr. Østergaard.

FACTS ABOUT MENDELIAN RANDOMIZATION:

Mendelian randomization (named after the Austrian monk Gregor Mendel, who was the father of modern genetics) is a method which in recent years has helped researchers to overcome a major challenge associated with observational studies - namely that of making causal inference. In observational studies researchers often find correlations between two conditions - e.g. between obesity and depression - where it is difficult, or rather impossible, to determine whether there is indeed a causal effect going from obesity to depression - or vice versa. Mendelian randomization may solve this challenge.

Mendelian randomization can be described as nature's version of the randomised controlled trials that are carried out when testing whether a new drug has the desired (causal) effect in the treatment of a disease. In the clinical trials of drugs, lots are drawn to determine whether individual participants will receive the active drug or a placebo, without them knowing which treatment they have been assigned to. Instead, Mendelian randomization takes advantage of the fact that a completely natural randomization takes place during the formation of the sex cells (egg cells and sperm cells), which represent the origin of all human beings. When sex cells are formed, the parents' genetic variants - including those that give rise to increased body fat- are randomly distributed. Therefore, some individuals will have received many of these variants and others less. In the study in question, the researchers have utilised this natural and random source of variation to determine whether people who have received many genetic variants for increased body fat have an increased risk of suffering depression.

THE RESEARCH RESULT - MORE INFORMATION

Genetic epidemiological study utilising data from the UK Biobank (with information on the association between genetic variants and fat mass based on a study of 330,000 people) and the Psychiatric Genomics Consortium (with information on the association between genetic variants and depression based on a study of 135,000 people with depression and 345,000 control subjects).

The research group comprises Maria S. Speed, Oskar H. Jefsen, Anders D. Børglum, Doug Speed and Søren D. Østergaard - all from Aarhus University.

TAMPA, Fla. (Aug. 27, 2019) -- Lymphedema, resulting from a damaged lymphatic system, can be a debilitating disease in which excess protein-rich fluid (lymph) collects in soft tissues and causes swelling -- most often in the arms or legs. Symptom severity varies, but the chronic swelling can lead to pain, thickened skin, disfigurement, loss of mobility in affected limbs, and recurrent infections.

While lymphedema can be managed with massage and compression garments or electronic sleeve-like pumps, no treatment exists to address its underlying cause: the abnormal build-up of lymph fluid that expands tissue like a water-logged sponge.

Now, a mouse model study led by the University of South Florida (USF Health) Morsani College of Medicine has identified new cellular processes controlling development of the small valves inside lymphatic vessels, which prevent lymph fluid from flowing the wrong way back into tissues. The one-way valves work with muscles to help propel lymph fluid through the body and regulate flow. The new findings suggest that targeting signaling pathways involved in creating and maintaining lymphatic valves may one day be a viable therapy for patients coping with lymphedema.

The study was published online Aug. 27 in Cell Reports.

"We knew that lymph flow was required for the valves to form and function throughout life, but we did not know how the endothelial cells that make up the inner lining of lymphatic vessels can 'sense' the flow," said senior author Joshua Scallan, PhD, assistant professor in the USF Health Department of Molecular Pharmacology and Physiology. "This study is the first to identify signaling pathways by which cells sense and respond to the mechanics of flow to keep the valves operating effectively -- so that lymph fluid keeps moving forward."

The lymphatic circulatory system - a parallel system to the blood vessels - is an extensive drainage network that acts as a conduit for immune cells (such as lymphocytes) and helps protect the body against infections. One of its primary jobs is to remove extra fluid (mostly water containing proteins, lipids, and other substances) that continuously leaks from tiny blood vessels into surrounding tissues just under the skin, Dr. Scallan said.

The lymph vessels, which carry lymph around the body, collects the leaked fluid (as much as 12 liters a day) and transports it away from the tissues. This lymph fluid is checked and filtered for bacteria, viruses and other harmful substances by lymph nodes clustered in various areas of the body, and eventually returned to the blood circulatory system through veins in the neck. If forward lymph flow is blocked or impaired, fluid does not drain from the tissues and results in the disease known as lymphedema.

In a series of experiments, the researchers used a "conditional knockout" mouse model, developed in Dr. Scallan's laboratory, in which production of the junction protein VE-cadherin was inactivated in lymphatic vessels. The gene for VE-cadherin, located where neighboring cells lining lymph vessels connect, was deleted in mice both before and after birth.

Among key findings of the preclinical study detailed in Cell Reports:

Deletion of VE-cadherin prevented lymphatic valves from forming in the embryonic mice and caused disintegration of valves already developed in the postnatal mice. This indicates that the protein is required for lymphatic valves to form, mature and maintain the normal movement of lymph fluid away from tissues.

Stimulating two different signaling pathways dependent upon VE-cadherin activation -- β-catenin and AKT - partially rescued the loss of valves.

The AKT signaling pathway was shown to promote the growth of new valves in normal, healthy mice.

"Our data explain how fluid forces at the lymphatic endothelial cell membrane regulate genes to control valve formation and maintenance," Dr. Scallan and his fellow study authors concluded. "Future studies are needed to investigate the AKT signaling pathway to identify therapeutic targets that may safely enhance valve formation in lymphedema patients."

Millions of people worldwide suffer from lymphedema, predominantly in tropical and subtropical regions where filariasis (a parasitic infection) is common. In the U.S. and most other developed countries, acquired (secondary) lymphedema is most commonly caused by breast cancer treatment: surgical removal of lymph nodes or radiation therapy. Hereditary (primary) lymphedema, caused by defective lymph vessels at birth, is rare.

(Boston)--After decades of research, a new study links optimism and prolonged life.

Researchers from Boston University School of Medicine (BUSM), National Center for PTSD at VA Boston Healthcare System and Harvard T.H. Chan School of Public Health, have found that individuals with greater optimism are more likely to live longer and to achieve "exceptional longevity," that is, living to age 85 or older.

Optimism refers to a general expectation that good things will happen, or believing that the future will be favorable because we can control important outcomes. Whereas research has identified many risk factors that increase the likelihood of diseases and premature death, much less is known about positive psychosocial factors that can promote healthy aging.

The study was based on 69,744 women and 1,429 men. Both groups completed survey measures to assess their level of optimism, as well as their overall health and health habits such as diet, smoking and alcohol use. Women were followed for 10 years, while the men were followed for 30 years. When individuals were compared based on their initial levels of optimism, the researchers found that the most optimistic men and women demonstrated, on average, an 11 to 15 percent longer lifespan, and had 50-70 percent greater odds of reaching 85 years old compared to the least optimistic groups. The results were maintained after accounting for age, demographic factors such as educational attainment, chronic diseases, depression and also health behaviors, such as alcohol use, exercise, diet and primary care visits.

"While research has identified many risk factors for diseases and premature death, we know relatively less about positive psychosocial factors that can promote healthy aging," explained corresponding author Lewina Lee, PhD, clinical research psychologist at the National Center for PTSD at VA Boston and assistant professor of psychiatry at BUSM. "This study has strong public health relevance because it suggests that optimism is one such psychosocial asset that has the potential to extend the human lifespan. Interestingly, optimism may be modifiable using relatively simple techniques or therapies."

It is unclear how exactly optimism helps people attain longer life. "Other research suggests that more optimistic people may be able to regulate emotions and behavior as well as bounce back from stressors and difficulties more effectively," said senior author Laura Kubzansky, PhD, MPH, Lee Kum Kee Professor of Social and Behavioral Sciences and co-director, Lee Kum Sheung Center for Health and Happiness at the Harvard T.H. Chan School of Public Health. The researchers also consider that more optimistic people tend to have healthier habits, such as being more likely to engage in more exercise and less likely to smoke, which could extend lifespan. "Research on the reason why optimism matters so much remains to be done, but the link between optimism and health is becoming more evident," noted senior author Fran Grodstein, ScD, professor of epidemiology at the Harvard T.H. Chan School of Public Health and professor of medicine at the Channing Division of Network Medicine at Brigham and Women's Hospital and Harvard Medical School.

"Our study contributes to scientific knowledge on health assets that may protect against mortality risk and promote resilient aging. We hope that our findings will inspire further research on interventions to enhance positive health assets that may improve the public's health with aging," added Lee.

HOUSTON -- (Aug. 26, 2019) -- A cancer therapy invented at Rice University has crossed a milestone in clinical trials, a major development in a decadeslong quest to develop a treatment that destroys tumors without the debilitating side effects of chemotherapy, invasive surgery and radiation.

Thirteen of the first 15 prostate cancer patients treated in a clinical trial of the nanoparticle-based, focal therapy showed no detectable signs of cancer a year after treatment, according to a study published this week in the Proceedings of the National Academy of Sciences (PNAS).

The paper presents the results from 16 patients who were treated at the Icahn School of Medicine at Mount Sinai in New York. It is believed to be the first published clinical study of a photothermal cancer therapy -- one that uses illuminated nanoparticles to heat and destroy tumors -- in a refereed scientific journal, said the study's authors.

In the study, 16 men ages 58 to 79 with low- to intermediate-risk localized prostate cancer agreed to participate in a trial of AuroLase Therapy, a focal ablation treatment that uses gold nanoparticles to heat and destroy tumors. Fifteen of the 16 patients underwent the two-day treatment, receiving an intravenous infusion of nanoparticles on day one and undergoing an image-guided ablation treatment on day two. All of the patients went home on the day of the treatment and returned for follow-up tests at three months, six months and one year after treatment. Of the 15 who completed treatment, only two showed detectable signs of cancer in follow-up biopsies and MRIs one year later.

"Gold-silica nanoshell infusion allows for a focused therapy that treats the cancer while sparing the rest of the prostate, thus preserving a patient's quality of life by reducing unwanted side effects, which could include erectile dysfunction and/or the leakage of urine," said study lead author and trial principal investigator Dr. Ardeshir Rastinehad, associate professor of urology and radiology at the Icahn School of Medicine at Mount Sinai.

The trial, which is ongoing and has treated 44 patients at Mount Sinai and two other clinical sites in Michigan and Texas, is the culmination of a 20-year quest by Rice University engineer and nanoscientist Naomi Halas and Duke University bioengineer Jennifer West. Halas and West, co-authors of the new study, first envisioned the nanoparticle-based therapy around 2000 while working together in Rice's Brown School of Engineering.

The particles, tiny silica spheres with a thin outer layer of gold, are called nanoshells. They are about 50 times smaller than a red blood cell, and Halas invented them at Rice in 1997. By varying the thickness of the gold shell, Halas had shown she could tune nanoshells to interact with specific wavelengths of light. Around 2000, she and West invented a method of destroying cancer cells by heating nanoshells with a low-power, near-infrared laser that could pass harmlessly through healthy tissue.

The work garnered national awards and press coverage, and by the early 2000s Halas and West had co-founded a Houston-based startup, Nanospectra Biosciences, to develop the technology for clinical use.

Around that time, Halas' father, then 85, was diagnosed with prostate cancer.

"He had profound hearing loss and was legally blind, so I had to be the communications link between him and his urologist," Halas said. "I know a lot about what people go through with prostate cancer because of my dad."

Halas said she'll never forget when her father asked if her invention might be the answer for his prostate cancer.

"He knew about nanoshells," she said. "The story had been in Business Week, and he had posted the clipping on a wall in his office."

At the time, Nanospectra was still conducting the necessary pre-clinical work to show that nanoshells could be safely used in humans.

Two years after his radiation therapy, it became almost impossible for him to urinate.

"It was terrible," Halas recalled. "He was in and out of the hospital weekly. The doctor would catheterize him. He'd go home. Things would be fine for a few days, and then he'd have to go to the emergency room. It was unbelievable what he went through."

She vividly recalls a conversation that still motivates her.

"He said to me, 'If you could prevent just one person from having to go through the hell that I went through, it would be worth it,'" Halas said.

From the outset, West and Halas had imagined a treatment that would destroy cancer without the debilitating side effects often associated with chemotherapy, invasive surgery and radiation. And that had been borne out in their early studies in cell cultures and mice.

"The science hasn't changed," West said. "If you look back to our original PNAS paper, where we did the first animal studies, there's nothing fundamentally different in the science."

But getting clinical trials approved by the Food and Drug Administration was not easy, in part because the technology was groundbreaking.

"We were the first, really engineered nanoparticle to go into human beings," West said. "In the beginning, the FDA wasn't sure how to handle these types of materials. We had something that looked like an injectable liquid in an IV bag. Was it a drug or a device? There was a point in time where the FDA was discussing creating a whole new division just for nano."

In the end, the agency opted to regulate the treatment, which Nanospectra branded as AuroLase Therapy, as a medical device. Clinical trials focused on safety began almost 10 years ago with a study in late-stage head and neck cancer. Halas said Nanospectra learned valuable lessons at every step, but she said it was another big advance -- this one in medical imaging -- that set the stage for the success in prostate cancer.

In 2011, researchers from the National Institutes of Health published results of a new technique that combined ultrasound and MRI imaging to resolve prostate tumors with millimeter-scale precision, Halas said. Clinicians began adoption of the technique for "fusion biopsies," a procedure for targeting needle biopsies to the specific site of suspected tumors.

One of the lead researchers working to develop fusion biopsy technology was Rastinehad, who joined Mount Sinai in 2015 and was an early proponent of using the fusion imaging platform for "focal therapy," minimally invasive treatment that could target tumors without the risks of incontinence and impotency that were associated with whole-gland treatments like surgical removal of the prostate or radiation.

For Halas and West, the newly published study is another, important step in a 20-year journey that's always been personal and deeply moving.

"Tropical Storm Allison hit while we were doing our earliest animal experiments in the Texas Medical Center," West recalled. "Many of the MRI instruments in animal research facilities were destroyed, and we ended up having to run MRIs on our mice in the same facilities they were using to image patients. It was profoundly moving to see the impact that cancer was having on people, to be waiting there with them and think that what we were developing might one day, hopefully, really help them."

Halas' father died several years ago, but she said she thinks about him every day.

"There's a bigger picture here," she said. "This (study) is 16 men, but when does it get to be 16,000? Sixteen million? Because 1 in 9 men are going to have to deal with this in their lifetime. The thought that this treatment could alleviate the side effects, and the misery, that my dad experienced is truly heartwarming."

West said the results show what is possible when physicians and engineers work together to solve problems.

"This work demonstrates the power of collaboration across engineering and medicine," she said. "It shows how collaboration can enable the translation of exciting new technologies into clinical medicine to improve the lives of patients."

An innovative graphene-based film helps shield people from disease-carrying mosquitos, according to a new study funded by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. The research, conducted by the Brown University Superfund Research Center, Providence, Rhode Island, is published in the Proceedings of the National Academy of Sciences.

"These findings could lead to new protective methods against mosquitos, without the environmental or human health effects of other chemical-based repellants," said Heather Henry, Ph.D., a health scientist administrator with the NIEHS Superfund Research Program.

Researchers found dry graphene film seemed to interfere with mosquitos' ability to sense skin and sweat because they did not land and try to bite. When they looked closely at videos taken of the mosquitos in action, they noticed the insects landed much less frequently on graphene than on bare skin. The graphene film also provided a strong barrier that mosquitos could not bite through, although when wet it did not stop mosquitos from landing on skin.

"We set out imagining that graphene film would act as a mechanical barrier but after observing the mosquitos' behavior, we began to suspect they were not interested in biting," said Robert Hurt, Ph.D., director of the Superfund Research Program at Brown University.

Until this study, insect-bite protection was an unexplored function of graphene-based materials. Results show that graphene, a tight, honeycomb lattice of carbon, could be an alternative to chemicals now used in mosquito repellants and protective clothing.

Mosquitos threaten public health by carrying infectious viruses such as Yellow Fever, West Nile, and Zika, leading to disability and death for millions of people every year.

Several years ago, Hurt began devising suits with graphene to protect workers against hazardous chemicals at environmental clean-up sites. He pointed out a wealth of literature demonstrates graphene's impermeable qualities. Graphene is invisible to the unaided eye, yet harder than diamonds, stronger than steel, and more conductive than copper. Since its discovery in 2004, graphene has been used for a variety of barrier and filtration purposes.

"This innovation using graphene to repel mosquitos could help reduce the burden of ill health associated with a number of infectious diseases and might reduce the need for pesticides to eradicate the mosquitos that carry them," said William Suk, Ph.D., director of the NIEHS Superfund Research Program. "New material such as this one should be assessed in the field to determine full public health implications."

Targeting the mosquito population within a defined area is the primary way scientists and public health officials mitigate the spread of diseases caused by viruses like Zika, dengue fever, and West Nile. But researchers have discovered that evaluating how humans commute to and from an affected area, as well as their living habits, is key to successful mitigation planning, according to a study published in PLOS Neglected Tropical Diseases and coauthored by a University of Tennessee, Knoxville professor.

"We have advanced our understanding of how much information cities need to make good cost-effective public health decisions," said coauthor Nina Fefferman, a professor in UT's Department of Ecology and Evolutionary Biology.

For the study, researchers analyzed commuting patterns of people in San Juan, Puerto Rico; Recife, Brazil; and Jakarta, Indonesia. The cities were chosen because all three were recently exposed to Zika or dengue fever infections and have different patterns of human movement. People bitten and infected in one part of a city can spread the disease to a mosquito that bites them in another community.

The research team used the commuter flow and human distribution data to model different scenarios, informing the design of mosquito control strategies.

Based on the model results, researchers considered the optimal scale at which to implement interventions; how they planned their attack on the mosquitos was dependent on the behavior of the humans in those cities.

Different control scenarios were modeled as well. In all models where interventions were implemented, the severity of the outbreak was successfully limited.

Researchers also found that investment in control measures and the efficacy of those measures affect disease risks. The success of control strategies depends on a city's structure and human movement within the city.

There is not a one-size-fits-all approach that is economically and practically efficient, Fefferman warns. "But it means it's really important to know what kinds of information, and how much information, we need to inform public health policy in using our resources most effectively."

The paper is part of an ongoing project by Fefferman's research group to incorporate real-world constraints into epidemiological models to shape public health policy around controlling mosquito-borne infections.

Having simple text conversations with patients one week before they are scheduled for a colonoscopy dramatically decreased the "no-show" rates, according to a recent study conducted by Penn Medicine researchers. Through sending reminders and instruction, opening the door for patients to ask questions, and sharing helpful links, the team increased rate of colonoscopies to 90 percent--well above the 62 percent success rate seen in a group who did not receive this extra communication. The results of this study were published in Health Education & Behavior.

"Automated text messaging and new insights from behavioral science offer opportunities to effectively and efficiently engage with patients before important health prevention activities," said the study's senior author, Shivan Mehta, MD, MBA, an assistant professor of Medicine and the associate chief innovation officer at Penn Medicine. "It's also important to keep in mind that these programs should be conducted in close partnership with clinical operations, and that we understand patient perspectives about these interventions."

In the United States, colorectal cancer is the second-deadliest form of cancer. Despite the danger presented by this disease, one in three people are not up-to-date on screening. As such, doctors like Mehta and the study's lead author, Nadim Mahmud, MD, MPH, a Hepatology fellow at the Hospital of the University of Pennsylvania, are exploring how technology and the framing of messages affect screening rates.

In April 2018, the researchers asked 22 patients scheduled for outpatient colonoscopy to participate in their text messaging program, featuring automation and two-way messaging powered by Penn Medicine's Way to Health platform. These 22 patients were compared to 50 patients in the control group who received the standard paper instructions and phone call reminder.

Examples of the automated messages patients were sent included: a congratulatory text and colonoscopy date reminder upon enrollment; a reminder with the office's address linked and a prompt for any questions about the procedure one-week before the appointment; a nudge to pick up prep materials (such as sports drinks and laxatives) from the pharmacy five days prior; and messages to prompt each step of the prep sequence the night before the appointment.

If patients responded with questions to any of the text prompts -- which three-quarters of them did -- the queries were escalated to gastroenterology staff, who answered within 24 hours.

"We think text messaging is successful because it is patient-centered. It is already widely used by our patient population, does not require much effort by the patient to participate, and patients can read or respond whenever they choose," said Mahmud. "Texting is also especially appealing to health systems because it is scalable and efficient - it's a tactic many others have employed in order to communicate with patients."

While the texting dramatically increased rates of success and was popular among the patients, the study showed that it didn't actually change the quality of prep among patients compared to those who just got a reminder call and paper instructions. This aspect of the program will likely be examined somewhat closer in the next phase of this study, which is being conducted currently with roughly 750 patients.

"We are evaluating the effectiveness of this service among a broader population and, in this new trial, we are automating some aspects of recruitment and engagement so that it will be easier to scale to routine operations across multiple endoscopy clinics," Mehta explained.

Passion fruit woodiness caused by cowpea aphid-borne mosaic virus (CABMV), the disease that most affects passion fruit (Passiflora edulis) grown in Brazil, can be combated with a relatively simple technique.

A study published in the journal Plant Pathology shows that systematic eradication of plants with symptoms of the disease preserves the crop as a whole and keeps plants producing for at least 25 months.

The technique currently used to combat CABMV entails renewing the entire orchard every year. This is, of course, a costly procedure. According to the authors of the study, economic factors are critical for this crop, which is mostly grown by small producers.

CABMV occurs in all states of Brazil and impairs plant development. Passion fruit woodiness disease causes leaf mosaic, blisters, deformation and reduced fruit size, making the produce unmarketable. Vines are typically eliminated only when the disease is detected in the early stages of their life cycle. The researchers propose systematic roguing - removal of weak, diseased or abnormal plants - throughout the life of the crop.

The study was funded by FAPESP and CAPES, the Brazilian Ministry of Education's Coordination for the Improvement of Higher Education Personnel. It was conducted by Brazilian researchers affiliated with the University of São Paulo's Luiz de Queiroz College of Agriculture (ESALQ-USP), the Federal University of São Carlos (UFSCar) at Araras, the University of Southwest Bahia (UESB), and the Semiarid Agriculture Unit of the Brazilian Agricultural Research Corporation (EMBRAPA), as well as colleagues at Argentina's National Agricultural Technology Institute (INTA).

"Roguing is a technique that has been used to combat papaya disease in Espírito Santo state since the 1980s. After several experiments, it was found to be the best way to control papaya ringspot virus type P [PRSV-P]," said Jorge Alberto Marques Rezende, Full Professor at ESALQ-USP and principal investigator for the study, which began in 2010.

CABMV is transmitted by aphid saliva and spreads throughout an orchard in a few months. The aphid species in question do not colonize the plants but merely visit them, and insecticide is not effective for control purposes.

"Insecticide affects their nervous system but takes hours to kill them. Meanwhile, they're stimulated to feed on more plants, spreading the virus farther, so insecticide helps propagate the disease instead of controlling it," said David Marques de Almeida Spadotti, first author of the article. The research was part of Spadotti's postdoctoral fellowship at ESALQ-USP.

In previous experiments, the use of transgenic passion fruit plants and inoculation with attenuated variants of CABMV as a kind of vaccine also failed to control the disease. In this new study, an experimental orchard was planted in three areas belonging to ESALQ-USP in Piracicaba, São Paulo state, and two areas in Vitória da Conquista, southwestern Bahia. The experiments took place between 2013 and 2018. Approximately 100 healthy seedlings were planted in two areas of each city using trellises or T-shaped arbors connected by wires.

The vines were trained on the trellises and arbors for support but also to separate them so that the disease could easily be observed. Any buds with symptoms were identified and removed in weekly inspections.

In two other areas distant from the others, the same number of vines were planted using trellises and allowed to interlace without roguing, as in commercial plantations. The results of the two strategies were then compared.

In the absence of roguing, the virus spread throughout the crop in 120 days. In the areas submitted to systematic roguing, 8% of the vines were infected and removed after 180 days. In Piracicaba, only 16% had to be removed after 25 months, and the plants remained productive throughout this period.

The presence of CABMV in all infected or preventively removed vines was confirmed by PTA-ELISA serological testing.

"The symptoms appear eight days after inoculation of the virus on average. Roguing enables the grower to identify diseased plants visually and base control on visual inspection. Inspection should ideally be carried out at least once a week," Spadotti said.

Cultural change

According to the researchers, the next step in the study entails larger pilot plantings of 1,000-2,000 passion fruit vines. In addition to eradicating diseased plants, they plan to replace them with healthy plants. The idea is to maintain the orchard for three to four years and compare it with another orchard maintained in the conventional manner, in which all plants are replaced every year.

"Because passion fruit is semiperennial, this longer production period is more advantageous from an economic standpoint than complete annual substitution," said Rezende, principal investigator for the Thematic Project "Begomovirus and Crinivirus in Solanaceae", which also relates to viruses in food crops.

The researchers stress, however, that if the strategy is to succeed, it should be implemented by all passion fruit growers in any given region. In addition to other plantations, the virus can spread from old or abandoned orchards, which should be eliminated.

CABMV-susceptible wild species of passion fruit in forests near plantations may also spread the disease. One of the experimental areas in Vitória da Conquista failed for this reason. When the wild plants were eliminated, the incidence of CABMV was considerably reduced.

According to IBGE, the national statistics and census bureau, Brazil is the world's leading grower of passion fruit, with more than 550,000 metric tons produced in 2017.

Oncologists at VCU Massey Cancer Center were invited to co-author an editorial published in the Journal of Clinical Oncology providing expert commentary on findings from a large study conducted by German investigators that a modified drug combination may lead to a decreased chance of disease recurrence for women with high risk, HER-2 negative breast cancer.

Masey Ross, M.D., medical director of the Integrative Health Program and breast medical oncologist at Massey, and Charles Geyer, Jr., M.D., associate director for clinical research, Harrigan, Haw, Luck Families Chair in Cancer Research and breast medical oncologist at Massey, shed an optimistic light on the potential for a shift in the treatment protocol for an important subset of patients with early breast cancer.

Neoadjuvant chemotherapy (given before surgery) is the current standard of care for most women with lymph node positive or high risk, lymph node negative breast cancer. The regimen typically includes the use of the solvent-based drug paclitaxel (Taxol), which often contributes to allergic reactions and nerve damage in many patients.

Research reported by the German Breast Group (GBG) in 2016 had demonstrated that the substitution of the albumin-based drug nab-paclitaxel (Abraxane) instead of Taxol prior to surgery improved chances for a complete pathologic response at the time of surgery in patients with triple negative breast cancer, but not with other disease subtypes. A complete pathologic response refers to the elimination of all invasive cancer in the breast and lymph nodes.

Nab-paclitaxel was initially approved as a treatment for metastatic breast cancer in 2005.

New findings published by the GBG revealed that the groups of patients who received nab-paclitaxel instead of the standard paclitaxel before surgery experienced improved long-term outcomes, meaning more of them were alive and disease-free following their surgery. This was found to be the case for women with triple negative, hormone receptor positive and HER-2 positive breast cancers.

These findings challenge a prevailing viewpoint in oncology by suggesting that drugs that aren't effective in increasing the percentage of complete pathologic responses could still result in better long-term outcomes.

"The study is interesting because it makes us rethink whether drugs administered prior to surgery that do not improve chances of having a complete response should be discarded under the assumption that they will not decrease a patient's risk of recurrence after surgery," said Ross, who is also an assistant professor of internal medicine at the VCU School of Medicine.

While the GBG findings indicate that nab-paclitaxel was more effective than standard paclitaxel for breast cancer patients across the board, Geyer and Ross believe that these study results could be particularly important for one breast cancer subtype over the other types.

"In our opinion, this information is most applicable in women with hormone receptor positive, HER-2 negative breast cancer," said Geyer, also a member of the Developmental Therapeutics research program at Massey and a professor of internal medicine at the VCU School of Medicine. "We feel it may not be particularly relevant for patients with HER-2 positive breast cancer because substantial improvements in HER-2 directed therapies co-administered with chemotherapy in this subset have occurred since the German study finished accruing patients. The improvements seen with nab-paclitaxel came at a cost of increased rates of neuropathy, and alternative approaches available for patients with HER-2 positive breast cancer are associated with less neuropathy."

Neuropathy, a debilitating form of nerve damage, may prevent HER-2 positive breast cancer patients from being able to tolerate subsequent administration of highly effective drugs such as T-DM1 that are significantly beneficial for women who did not have a complete pathologic response at the time of surgery.

For triple negative breast cancer patients, some oncologists incorporate the use of a chemotherapy agent called carboplatin, which has been shown to improve chances for a complete response when administered before surgery. The study conducted by the GBG did not factor in the use of carboplatin; therefore, it remains unclear how nab-paclitaxel will interact with it for this patient group.

"We suggest that physicians who do not incorporate carboplatin into treatment for women with triple negative breast cancer should consider nab-paclitaxel over standard paclitaxel," Ross said.

PITTSBURGH, Aug. 26, 2019 - Over the course of a decade, out-of-pocket costs for multiple sclerosis drugs rose more than sevenfold for Medicare Part D beneficiaries, according to a JAMA Neurology study published today by researchers at the University of Pittsburgh.

Using Medicare claims data from 2006-2016, the researchers looked at trends in multiple sclerosis drug prices over time. Not only did they find steep increases in list prices -- the starting point before rebates, coupons or insurance kicks in -- but also in the ultimate costs to both Medicare and its recipients.

"We wanted to see how increases in list prices translated to increases in out-of-pocket spending, and we discovered that actual price increases do get passed down to patients, and that can negatively affect access," said study senior author Inmaculada Hernandez, Pharm.D., Ph.D., assistant professor of pharmacy at Pitt.

Several drugs on the market reduce the frequency and severity of multiple sclerosis flare-ups, which can involve a variety of disabling neurological symptoms, such as vision loss, pain, fatigue and muscle weakness.

From 2006-2016, the annual list prices of these drugs more than quadrupled, ballooning from about $18,000 to nearly $76,000 per patient per year.

Some of the most popular drugs for treating multiple sclerosis are Copaxone, Tecfidera and Avonex, and, despite increased market competition over time, prices have been rising steadily for nearly all of them.

"One of the most significant findings was that the prices of these drugs have increased in parallel," said lead author Alvaro San-Juan-Rodriguez, Pharm.D., a pharmacy fellow at Pitt. "Only a couple exceptions deviate from that general trend."

Although this trend among list prices is alarming on its own, critics have argued that since some of the cost is canceled out by manufacturer rebates and other kinds of discounts, rising list prices may not be translating into increased spending.

But since Medicare claims provide a detailed cost breakdown, the researchers were able to measure changes in what Medicare Part D beneficiaries actually paid out of pocket for multiple sclerosis drugs, as well as what Medicare itself paid.

What they found was that from 2006-2016, Medicare spending increased by more than tenfold, and the patients themselves saw more than a sevenfold increase in their share of the bill.

"We're not talking about patients without health insurance here," Hernandez said. "We're talking about insured patients, under Medicare. Still, they are paying much more for multiple sclerosis drugs than they were 10 years ago."

PROVIDENCE, R.I. [Brown University] -- Brown University researchers have developed a simple method for isolating placental cells from cervical swabs. The technique, described in the journal Scientific Reports, could aid in developing less invasive ways of diagnosing genetic disorders in developing fetuses.

The technique isolates trophoblast cells -- placental cells that carry the complete fetal genome -- by taking advantage of their tendency to settle to the bottom of microwell plates. The researchers lay out a procedure for optimally isolating the cells, enabling them to be picked individually from the plate.

"This is the first study to use cell settling for enriching trophoblast cells from a heterogeneous cervical cell population," the researchers write. "Ultimately, we provide a technique that is quick, inexpensive, minimizes cell loss, and results in retrieval of individual trophoblast cells."

The work was led by the lab of Anubhav Tripathi, a biomedical engineering lab at Brown that specializes in lab-on-a-chip diagnostics -- in collaboration with the Shukla Lab for Designer Biomaterials at Brown's School of Engineering, led by Anita Shukla, and with PerkinElmer, Inc.

Currently, the only way to diagnose genetic disorders in developing fetuses is by retrieving trophoblasts through amniocentesis or chorionic villus sampling, both invasive procedures that carry a small risk of miscarriage. Blood tests that look for fetal genetic material in the mother's bloodstream can be useful screening tools, but they can't be used for definitive diagnosis. And screening is limited to whatever genetic material happens to turn up in the blood, which limits the range of disorders that can be screened.

Trophoblasts are known to be present in the cervical canal in the early stages of pregnancy, but the quantities are small, and isolating those cells from cervical cells and mucus is difficult. For this new study, a team of researchers led by Christina Bailey-Hytholt, a Ph.D. candidate in biomedical engineering at Brown, wanted to see if there were any physical characteristics of trophoblasts that might help in isolating them from cervical cells and other material.

The researchers found that trophoblasts are smaller than cervical cells, differ in shape and have relatively large nuclei. Those characteristics suggested that they may settle more quickly than cervical cells when cell mixtures are placed on microwell plates.

Using polystyrene plates, the researchers found that the trophoblasts did indeed settle more quickly than cervical cells. The study showed that the maximum separation of cell types was achieved around four minutes after the cells were put on the plate. At that point, the cervical cells and mucus on top of the cells could be removed, leaving a large concentration of trophoblasts behind. The technique increased the proportion of trophoblasts in samples by 700%, enabling individual trophoblasts to be picked out for genetic testing.

No specialized equipment beyond what any diagnostic lab would already have is required to perform the technique, the researchers say. And takes only a few minutes to produce the cells necessary for genetic testing.

"There is a large need for biomedical engineering techniques toward advancing prenatal and women's health," Bailey-Hytholt said. "Our work is a step toward more non-invasive prenatal testing options."

AUGUSTA, Ga. (Aug. 26, 2019) - Heart muscle can continue to die even after restoring blood following a heart attack, and scientists have new evidence that one way to help it live is by boosting levels of a tiny RNA that helped the heart form.

In their mouse model of this ischemia/reperfusion injury of the heart, they've found they can reduce heart muscle death 40 percent by giving a manmade version of the microRNA miR322, they report in the Journal of Molecular and Cellular Cardiology.

MiR322 is known to coax stem cells to make heart cells during development but is typically found at a lower, more basal level and with an unclear purpose in the adult heart, says Dr. Yaoliang Tang, cardiovascular researcher in the Vascular Biology Center and Department of Medicine at the Medical College of Georgia at Augusta University.

Tang and his team were looking for better ways to protect the heart from additional damage, doing high throughput analysis of microRNAs, which help regulate gene function, and miR322 was the first standout as the most dramatically reduced after blood flow to the heart was restored.

So Tang's team began looking for the source of miR322 in adult hearts -- which turned out to be the endothelial cells that line the blood vessels -- and in the process they also found miR322's target.

For these studies, they caused an occlusion in the left coronary artery of mice for about 45 minutes, then enabled reperfusion to reflect what happens when a human has a heart attack, then gets treatment. During the period of ischemia --when the heart attack happens -- they saw seriously reduced miR322 levels, which recovered after blood and oxygen were restored but dropped dramatically again one day later, the lowest point was seven days later.

When they increased miR322 by giving what scientists call its mimic, they saw levels of the endogenous heart cell protector Notch 1 significantly increase while levels of cell suicide promoter FBXW7 significantly decreased, and heart damage reduced.

When they gave both miR322 mimic and FBXW7 plasmid -- a plasmid is small DNA molecule, which can be used to increase expression of a gene -- Notch 1 levels instead decreased and the heart benefit was lost, implicating FBXW7 as a direct target of miR322.

"We still need to see how and if it can protect the heart long term, but we find in the short term when we give enough of this microRNA, it protects the heart from reperfusion injury," Tang says.

While the half-life of miR322 is just a few seconds and it's very expensive, it likely could one day be used in the immediate aftermath of a heart attack to reduce permanent heart damage, Tang says. A great therapeutic advantage is that it's so small it's easily taken up by heart cells, he adds. Still a better option might be finding a way to instead bolster the body's natural method for increasing miR322, which the team is now looking to find.

Heart disease is the leading cause of death in Georgia and the United States, according to the Centers for Disease Control and Prevention.

Inadequate blood and oxygen to the heart, or ischemia, resulting from a clot or other occlusion of a big blood vessel in the heart, is the primary problem. However solutions, including cardiac bypass surgery and angioplasty to reopen blocked coronary arteries, can result in a second period of adjustment and injury that can be responsible for as much as half of the size of the damage done to the heart muscle, called the infarct size.

If it seems odd that reestablishing blood rich in oxygen and nutrients back to heart cells that are screaming for both and dying without them, would also cause injury, Tang explains that it's a fragile transition period. When oxygen levels drop, heart cells' metabolic rate drops as well to reduce their needs, much like cooling the body during cardiac surgery.

"Heart cells are fragile and when oxygen reenters they need to switch back to their normal metabolic rate," Tang says. "A lot of cells just don't adjust well and will die."

The state of ischemia also produces and recruits a variety of factors and cells that promote inflammation to help protect from infection and haul off debris from dying cells. This highly inflammatory state produces a lot of free radicals, unstable atoms that can cause even more damage to heart cells. "That is why a lot of patients don't die because of ischemia, they die because of reperfusion," Tang says.

Notch 1 signaling is an endogenous method of protecting the heart from oxidative stress that can prevent cell suicide -- which is in direct conflict with the tagging for death work of FBXW7 -- so here FBXW7 modifies active Notch 1 so it can't function.

FBXW7 is called an ubiquitin enzyme, because it adds the small molecule ubiquitin to proteins, which basically tags them for delivery to the garbage. "It's a bad enzyme," says Tang. In this scenario, one of the things it's modifying is active Notch 1 and when FBXW7 goes us up, miR322 goes down. In fact, there is not just an association of the two but miR322 typically regulates FBXW7, physically binding to it to keep it from doing anything bad. When ischemia reduces miR322 levels, FBXW7 is freer to tag and eliminate, Tang says.

MiR322 overexpression, which increases Notch 1, has been shown to have similar protective effects in the brain, where an ischemic stroke has pretty much the same effect as a heart attack.

MiR322, called miR-424 in humans, was known to show up following ischemia but where it came from and what exactly it was doing remained unknown.

Next steps include studies in a larger animal model, and Tang also wants to learn more about two other microRNAs that seem to function as partners to miR322. Because while miR322 was the first microRNA they found dramatically impacted, they would also find two others whose levels seemed to rise and fall in tandem with miR322's. There is clearly crosstalk between them, Tang says.

(Boston)--Heavy alcohol consumption (three drinks or more/day for women and four drinks or more/day for men) is linked to alterations in immune function among people with HIV.

While it has been known that alcohol impacts immune function, it's been unclear the effect of alcohol on immune function in the context of HIV, a disease whose progression is dependent on immune dysfunction.

Researchers from Boston University School of Medicine (BUSM) looked at biological markers of innate immune function, a kind of immune response that acts quickly and non-specifically to new infections and pathogens. They investigated biological markers of three specific immune processes: systemic inflammation, monocyte activation and altered coagulation. Higher levels of biological markers for these processes have previously been associated with higher risk of death. In the current study, the researchers assessed self-reported alcohol use over time (three times over two years) and also measured alcohol use using a blood-based marker of alcohol consumption called PEth (phosphatidylethanol) that detects alcohol consumption up to about 21 days after drinking. Additionally they measured other behaviors and health conditions that could obscure the true relationship between alcohol consumption and these biomarkers.

"We found that people who reported drinking more alcohol or had high PEth had higher levels of these biomarkers of immune function. The fact that heavy alcohol consumption was linked to elevated levels of these biomarkers, which are linked to mortality, suggests that alcohol may be contributing to mortality risk through immune dysfunction among people with HIV," said corresponding author Kaku So-Armah, PhD, assistant professor of medicine at BUSM.

According to the researchers, it is important to note they observed elevated levels of these biomarkers of immune activity in a relatively young HIV population with a low occurrence of chronic inflammatory diseases of aging like diabetes, obesity or renal disease. "Further we observed that the relationship between alcohol consumption and some of these biomarkers was not linear, suggesting a complex relationship between alcohol use and biomarkers of systemic inflammation and monocyte activation."

While the researchers stress that this is an observational study and the findings do not prove causality, they hope the study highlights the harms associated with heavy alcohol consumption among people living with HIV.

HOUSTON - (Aug. 22, 2019) - How do you know a cell has a fever? Take its temperature.

That's now possible thanks to research by Rice University scientists who used the light-emitting properties of particular molecules to create a fluorescent nano-thermometer.

The Rice lab of chemist Angel Martí revealed the technique in a Journal of Physical Chemistry B paper, describing how it modified a biocompatible molecular rotor known as boron dipyrromethene (BODIPY, for short) to reveal temperatures inside single cells.

The molecule is ideally suited to the task. Its fluorescence lasts only a little while inside the cell, and the duration depends heavily on changes in both temperature and the viscosity of its environment. But at high viscosity, the environment in typical cells, its fluorescence lifetime depends on temperature alone.

It means that at a specific temperature, the light turns off at a particular rate, and that can be seen with a fluorescence-lifetime imaging microscope.

Martí said colleagues at Baylor College of Medicine challenged him to develop the technology. "Everybody knows old thermometers based on the expansion of mercury, and newer ones based on digital technology," he said.

"But using those would be like trying to measure the temperature of a person with a thermometer the size of the Empire State Building."

The technique depends on the rotor. Martí and Rice graduate student and lead author Meredith Ogle constrained the rotor to go back and forth, like the flywheel in a watch, rather than letting it rotate fully.

"It pretty much wobbles," Martí said.

"What we measure is how long the molecule stays in the excited state, which depends on how fast it wobbles," he said. "If you increase the temperature, it wobbles faster, and that shortens the time it stays excited."

The effect, Martí said, is conveniently independent of the concentration of BODIPY molecules in the cell and of photobleaching, the point at which the molecule's fluorescent capabilities are destroyed.

"If the environment is a bit more viscous, the molecule will rotate slower," Martí said. "That doesn't necessarily mean it's colder or hotter, just that the viscosity of the environment is different.

"We found out that if we constrain the rotation of this motor, then at high viscosities, the internal clock -- the lifetime of this molecule -- becomes completely independent of viscosity," he said. "This is not particularly common for these kind of probes."

Martí said the technique might be useful for quantifying the effects of tumor ablation therapy, where heat is used to destroy cancer cells, or in simply measuring for the presence of cancers. "They have a higher metabolism than other cells, which means they're likely to generate more heat," he said. "We'd like to know if we can identify cancer cells by the heat they produce and differentiate them from normal cells."