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Public health experts report August 22 in the journal Cell that surveillance of international travelers for infectious disease can help reconstruct unreported or undetected outbreaks of Zika and other viruses. By sequencing virus genomes from infected travelers, analyzing travel patterns and mosquito modeling, the researchers unearthed a spike in Zika cases from travelers returning from Cuba during the summer of 2017 that was not captured by local reports, says study co-author Nathan D. Grubaugh (@NathanGrubaugh), an epidemiologist at the Yale School of Public Health.

Three years ago, a well-publicized Zika epidemic in Brazil was tied to microcephaly and other congenital abnormalities. Zika is also associated with neurologic disorders, including Guillain-Barré syndrome. However, disparities in data make it unclear whether the virus--transmitted by the mosquito Aedes aegypti--is still a threat in the Americas.

"As the larger Zika epidemic in the Americas appeared to be waning towards the end of 2016, we became interested in understanding whether the epidemic was truly gone or whether 'hidden' transmissions could still be occurring," says study co-author Scott F. Michael, a biologist at Florida Gulf Coast University.

Accurately pinpointing cases of Zika can be challenging: its symptoms mimic those of other diseases; and regions with inadequate health care systems often lack reliable, inexpensive diagnostic tools. Early and rapid pathogen detection is critical in preventing outbreaks from spinning into large-scale epidemics, says co-author Kristian Andersen, an infectious disease researcher at Scripps Research.

Based on travel incidence rates reported by other countries, in 2017, Cuba would have experienced 1,000 to 20,000 Zika cases, Andersen says. However, only 187 cases were reported in 2016 and none in 2017.

Between June 2017 and October 2018, more than 98 percent of the travel-associated cases reported in Florida and Europe came from Cuba. The timing of this outbreak was a mystery: conditions in Cuba could have supported a large Zika outbreak in 2016. Why did Cuba's cases jump in 2017?

The main resource for reporting Zika cases is the Pan-American Health Organization (PAHO), which relies on local case reporting from member countries. To check the accuracy of PAHO results, the researchers sequenced Zika virus genomes from infected travelers in Florida and detected the unreported spike in cases in 2017.

The researchers determined that the delay was likely caused by a successful mosquito eradication campaign that had taken place in Cuba in 2016. "We show that the 2017 Zika outbreak was sparked by long-lived lineages of Zika virus introduced a year prior," Grubaugh says. "Our data suggest that while mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures may need to be maintained to be effective."

WASHINGTON -- Researchers at Georgetown Lombardi Comprehensive Cancer Center have decoded a chain of molecules that are critical for the growth and survival of pancreatic ductal adenocarcinoma (PDAC) - the most common and also the most lethal form of pancreatic cancer.

They say their findings, published in Developmental Cell, suggest that inhibiting this "Yap" biological network may effectively regress early stage PDAC and could be paired with other drugs to halt more advanced stage tumors. Yap inhibitors have been developed and are moving into clinical trials.

Their study builds upon Georgetown Lombardi research that previously identified Yap as an oncogene central to the initiation of PDAC as well as a variety of other cancers. In the current study employing advanced animal models, they have managed to switch off Yap in pre-established PDAC tumors, and discovered that suppressing Yap blocks the metabolic pathways that provide the fuel and building materials for maintaining the growth of the cancer.

This study revealed the "flow chart" of key molecules in the Yap signaling network, which could be used to design novel and more effective therapies for advanced pancreatic cancer, says the study's senior investigator, Chunling Yi, PhD, associate professor of oncology at Georgetown Lombardi.

"Our research suggests that inhibiting Yap as well as Sox2, a molecule that gets turned on when Yap is inhibited, could be very important to long-term control of pancreatic cancer," says Yi. "In later stages of this cancer, when a Yap inhibitor is used, Sox2 could takes its place to allow PDAC to survive and grow, so therapy that targets both molecules would be ideal."

Five-year survival for PDAC is in the single digits because 80 percent of patients are diagnosed with late-stage disease. Although the disease is the 12th most common cancer in the U.S., it is the 4th leading cause of cancer death, according to the National Cancer Institute.

The vast majority PDAC (95%) is caused by a mutation in an oncogene known as Kras, which keeps cell growth switched on. There is no approved treatment for tumors with Kras mutations, which are found in a number of cancers.

Kras mutations activate the Yap pathway. Yi and her colleagues, which include investigators from Germany and France, show, in animal models, that the Yap protein is required for the maintenance of Kras mutant PDAC tumors.

In preclinical work, Yi demonstrated that inhibiting Yap can force PDAC tumors to regress into cells that resemble what are normally found within the organ. Eventually, however, Sox2 is activated to compensate for loss of Yap, causing some tumors to relapse.

"To effectively control tumor growth, you have to know the molecular network that drives that growth. This study takes a good look under the hood and gives us the key drivers that could be targeted to shut that engine down," Yi says.

BOSTON - A gene that can become mutated and cause a rare balance disorder also regulates the behavior of an enzyme that increases the risk for Alzheimer's disease (AD), according to a new study by researchers at Massachusetts General Hospital (MGH) to be published in the journal Cell on August 22, 2019. This discovery may help to identify new targets for experimental medications designed to delay or stop the onset of AD.

In 2008, neuroscientist Rudolph E. Tanzi, PhD, director of the Genetics and Aging Research Unit and co-director of the McCance Center for Brain Health at MGH, and his colleagues identified several genes that are closely associated with AD. They include ATXN1, which carries the genetic code for producing a protein called ataxin-1. At the time, it was already known that a variation known as a "gain of function" mutation in ATXN1 causes a condition called spinocerebellar ataxia type 1 (SCA1), which afflicts one to two people per 100,000 worldwide. SCA1 leads to loss of coordination and balance, among other symptoms, which can include cognitive problems such as learning and memory difficulties.

However, the ATXN1 mutation that causes SCA1 is not associated with AD, and the role ataxin-1 might play in the disease remained unknown. "So the big question facing us was, How does a gene involved in a balance disorder somehow increase the risk for Alzheimer's disease?" says Tanzi, senior author of the Cell paper.

The answer to that question eventually came by posing another. "We asked whether loss of ataxin-1 function could lead to Alzheimer's disease," says MGH neuroscientist Jaehong Suh, PhD. Suh supervised a team that crossbred mice that were specially bred to have the ATXN1 gene deleted, causing them to lack ataxin-1, with a second group of mice that had been bred to have AD (AD mice). These pairings produced offspring that were missing ataxin-1, which in turn made their levels of an enzyme called beta-secretase 1 (BACE1) to rise dramatically.

BACE1 plays an essential role in the formation of amyloid plaques, which are clusters of damaged nerve cells and other proteins in the brain that are one of the hallmarks of AD. To be sure, mice lacking ataxin-1 had significantly greater deposits of amyloid plaque than the AD mice. They also had higher levels of inflamed brain tissue, formed fewer new neurons in regions associated with memory and learning, and had impaired axons, which are fibers that carry signals between neurons.

"The idea that the same protein will cause one neurodegenerative disease in a 'gain' situation, and cause vulnerability to another neurodegenerative disease in a 'loss' situation, is fascinating," says neurogeneticist Huda Y. Zoghbi, MD, a professor at Baylor College of Medicine, director of the Jan and Dan Duncan Neurological Research Institute in Houston, and a coauthor of the Cell study.

Several experimental drugs that block BACE1 have failed due to toxicity, but discovering ataxin-1's role in regulating this enzyme "could provide a new avenue to safely stop formation of amyloid plaques and potentially prevent this disease before it causes symptoms," says Tanzi.

WASHINGTON, Aug. 22, 2019 -- Many forms of birth control are hormone-based, but not everything mixes well with those hormones. This week on Reactions, learn about some common products that could make your birth control less effective or cause dangerous side effects: https://youtu.be/34tp9CCpOA0.

Reactions is a video series produced by the American Chemical Society and PBS Digital Studios. Subscribe to Reactions at http://bit.ly/ACSReactions, and follow us on Twitter @ACSreactions. For more of the latest research news, journalists and public information officers are encouraged to apply for complimentary press registration for the ACS fall 2019 national meeting in San Diego.

Surgeons wielding their life-saving scalpels, laparoscopic tools, or other implements to repair or remove what ails their patients understand all too well that pain is an unavoidable part of the healing process. Yet the current opioid crisis has made the standard prescribing practices for these highly effective analgesics fraught with risk.

New research from Michigan Medicine could help clinicians mitigate that risk by identifying which patients are more likely to continue to use opioids after their immediate recovery period.

"There is not much research on which surgical patients require more or less opioids, despite a push in the field for personalized medicine," says first author Daniel Larach, M.D., M.T.R., M.A., a resident at U-M at the time of the study and now assistant professor of clinical anesthesiology at the University of Southern California.

"Often with postoperative opioid prescribing, personalization falls by the wayside, with surgeons using the same amounts for every person receiving a certain procedure."

He and the study team looked at data for more than 1,000 people undergoing an elective hysterectomy, thoracic surgery, or a total knee or hip replacement. Before their procedures, each patient provided demographic information and filled out several screening questionnaires. They were given scores measuring their degree of depression, anxiety, fatigue, sleep disturbance, physical function, as well as the severity of their overall and surgical site pain. The research team also measured how many pills were prescribed per patient. Each patient was then contacted one month following surgery to assess how many opioid pills they had consumed.

"We found that anxiety is linked with more opioid use, which is disheartening to see but also heartening in the sense that this is something we could potentially target," says Larach.

Other patient factors linked to increased opioid use included younger age, non-white race, no college degree, alcohol and tobacco use, and sleep disturbance.

Chad Brummett, M.D., associate professor of anesthesiology and director of anesthesia clinical research and pain research, says people may be knowingly or unknowingly medicating for other conditions.

"The only thing we're giving them is opioids and we're not giving them alternatives or other options," he says. For example, patients with high anxiety around the time of surgery could be offered behavioral care or other non-opioid medications for anxiety and resulting pain.

Brummett, senior author on the Annals of Surgery paper, also notes that this study found overprescription of opioids for all surgical procedures and a correlation between the prescription size and use.

"I think it is striking that you see once again that the more you prescribe, the more patients take, even after adjusting for all of these other risk factors," explains Brummett.

Larach and Brummett note that right-sizing prescriptions through initiatives such as the Michigan Opioid Prescribing Engagement Network (OPEN), which provides recommendations for prescription amounts for various medical procedures, is a critical first step. But, they say, this step should be followed by more research into specific patient factors that can be addressed in other ways.

Says Brummett, "We are asking surgeons to learn about and think about pain and behavioral health in ways that we have not previously done. It will require an open mind."

Every year, more than 250,000 women in the U.S. are diagnosed with breast cancer. When detected early, patients with the most common form--which tests positive for hormone receptors (HR+) and negative for the HER2 receptor--usually respond well to treatment. But for those in advanced stages, few treatment options existed until the recent emergence of a new class of drugs known as CDK4/6 inhibitors.

These inhibitors showed remarkable efficacy in blocking tumor growth, halting disease progression and boosting survival, leading the FDA to fast-track the approval of three such drugs to date. Today, they are used as frontline medications for patients with advanced, HR+/HER2- breast cancers. While these drugs have the same biological targets and are often used interchangeably, a growing body of evidence suggests they have important underlying differences.

Now, Harvard Medical School researchers based in the Laboratory of Systems Pharmacology at the Blavatnik Institute and the Massachusetts General Hospital have carried out the first head-to-head comparison of the three currently approved CDK4/6 inhibitors in breast cancer cell lines and animals.

Their findings, published Aug. 15 in Cell Chemical Biology, reveal significant and thus far poorly understood differences in biological activity among members of a drug class designated as breakthrough therapies by the FDA. One inhibitor in particular--abemaciclib--exhibited unique and potentially advantageous therapeutic activity that could help inform the design of better treatment strategies, including optimized combination therapies and circumventing drug resistance, the authors said.

"Despite the sophistication of industrial drug discovery, the activities of many drugs are not fully understood at the time of their approval by the FDA," said senior study author Peter Sorger, the HMS Otto Krayer Professor of Systems Pharmacology in the HMS Department of Systems Biology and director of the Laboratory of Systems Pharmacology. "In this case, it appears that the drug abemaciclib may unexpectedly work in patients who are not responsive to other drugs in the class."

In their study, Sorger and colleagues, spearheaded by co-first authors Marc Hafner and Termeer Fellow Caitlin Mills, partnered with investigators based at the Termeer Center for Targeted Therapies at Mass General to form a cross-disciplinary team with the basic science and clinical expertise needed to comprehensively compare the drugs.

"Characterizing the exact target inhibition profile and the biological effects of these therapeutic agents is essential, because in some instances these differences may explain why one works and why another doesn't," said study co-senior author Dejan Juric, director of the Termeer Center. "Thorough and carefully designed studies are the only way to understand how best to sequence or combine these transformative drugs, and to identify which will be most beneficial for any individual patient."

Breakthrough family

Cells rely on a family of proteins known as CDKs (cyclin-dependent kinases) to control the complex process of cell division. These proteins are often dysfunctional in cancer cells, fueling aberrant division and uncontrolled cell growth. Early attempts to block CDK activity in tumors resulted in unsuccessful clinical trials as first-generation inhibitors affected a broad range of CDK proteins, causing the indiscriminate death of both normal and cancerous cells.

In 2015, the FDA approved palbociclib, a promising drug designed to target exclusively the CDK4 and CDK6 proteins. This high specificity led to dramatic improvements in halting tumor growth and extending progression-free survival with reduced toxicity. Two other CDK4/6 inhibitors, abemaciclib and ribociclib, were approved shortly after, all for patients with advanced HR+/HER2- breast cancer.

Although approved for the same clinical indications, these drugs differ in their chemical structures. Despite reports of different side effects in patients, it remained unclear whether they were indeed functionally equivalent.

To investigate, Sorger, Juric and colleagues applied a series of powerful experimental approaches. Over the course of several years, the team profiled the molecular activity of each of the three CDK4/6 inhibitors across a wide range of doses and dosage timings in cell lines and animal models. They analyzed the effects of these drugs on cellular growth rate, viability, gene expression and protein activity, among other indicators.

Sweet spot

Tests on a panel of 35 different breast cancer cell lines revealed a key difference in the drugs' biological activity. As expected for CDK4/6-specific inhibitors, all three agents stopped the growth of cells, the analyses showed.

At higher doses, however, only abemaciclib caused significant cancer cell death, suggesting the drug may be affecting proteins other than only CDK4/6. Palbociclib and ribociclib had minimal effects on cell death even when administered at higher doses.

Further analyses confirmed that abemaciclib has a unique profile. The drug most potently inhibited CDK4/6, and at high dosages, it also affected the activity of other proteins, acting in some ways as a pan-CDK inhibitor. Tests in mice transplanted with human breast cancer tumors affirmed these observations.

In additional experiments, the researchers developed breast cancer lines resistant to the drug palbociclib, a common occurrence that also affects patients in the clinic. These cell lines were unaffected by ribociclib, with cells continuing to grow and proliferate, but did respond to treatment with abemaciclib. Cells engineered to be unaffected by CDK4/6 inhibition also responded to abemaciclib, but not the other two drugs--further evidence of abemaciclib's pan-CDK activity.

"Whether by accident or design, abemaciclib appears to have hit a sweet spot where it is more efficacious in some regards than the other CDK4/6 inhibitors, but potentially less toxic than earlier pan-CDK inhibitors," said study co-author Kartik Subramanian, HMS postdoctoral fellow in the Laboratory of Systems Pharmacology.

Based on these results, the authors suggest that abemaciclib may have additional therapeutic benefits for a subset of tumors that remain unresponsive to treatment or have grown resistant to other CDK4/6 inhibitors. They cite a case study in which a patient's metastatic tumor reappeared after she developed resistance to palbociclib. She was switched onto abemaciclib, resulting in a notable decrease in tumor size, and continued to be successfully treated with the drug.

However, the authors caution that their study was based on preclinical, laboratory-based experiments and their findings do not present conclusions that should be used for decision-making in the clinic at this time. Rather, their data lay the necessary foundation for the design of clinical studies that can carefully and thoroughly assess which strategies for CDK4/6 inhibitor treatment would be of greatest benefit to patients.

Importantly, the same head-to-head comparison approach to profile similar drugs could be applied to other classes of drugs, the authors said.

"Our findings are an important reminder that just because drugs are marketed to have the same nominal targets, it doesn't mean they are necessarily equally effective in all situations," Mills said. "The most common form of breast cancer is hormone receptor positive, and for CDK4/6 inhibitors, there is the potential to make an enormous difference for a very large number of women by understanding how these drugs could be optimally used."

"The study also highlights the complex and often surprising ways, in which independent but complementary research by scientists in industry and academia can advance precision medicine," Sorger said.

PROVIDENCE, R.I. [Brown University] -- A team of Brown University researchers has developed a new computer model that simulates the way red blood cells become misshapen by sickle cell disease. The model, described in a paper published in Science Advances, could be useful in the preclinical evaluation of drugs aimed at preventing the sickling process.

"There are currently only two drugs approved by the FDA for treating sickle cell disease, and they don't work for everyone," said Lu Lu, a Ph.D. student in the Division of Applied Mathematics at Brown and the study's co-lead author. "We wanted to build a model that considers the entire sickling process and could be used to quickly and inexpensively pre-screen new drug candidates."

Sickle cell disease is a genetic disorder that affects millions of people worldwide. The disorder causes red blood cells, which are normally soft and round, to become stiff, sticky and sickle-shaped (a bit like a crescent moon). The irregularly shaped cells get stuck in blood vessels, causing pain, swelling, strokes and other complications.

At the cellular level, sickle cell disease affects hemoglobin, a protein in red blood cells responsible for transporting oxygen. When oxygen-deprived, sickle cell hemoglobin clumps together inside the cell. The clumps then form long polymer fibers that push against the cell wall, stiffening the cells and forcing them out of shape.

George Karniadakis, a professor of applied mathematics at Brown and senior author of the new research, has worked for years to better understand the disorder. Most recently, he's worked with Lu and He Li, a research professor at Brown, to create detailed biophysical models of each stage of the sickling process, including a model of red blood cell function called OpenRBC and a supercomputer model of sickle cell fiber formation.

This new model combines and simplifies the previous models to create a single kinetic model of the entire sickling process. Using information gleaned from the detailed supercomputer models, the researchers were able to build a simplified version that captures all the important dynamics of the sickling process, yet can be run on a laptop.

To validate the model, the researchers showed that it could reproduce the outcomes of prior experiments in the lab and in people.

Because the dynamics of the sickling process can vary depending upon where in the body it's happening, researchers designed the model to simulate sickling process in different organs. For example, because oxygen plays a key role in the process, sickling unfolds very differently in oxygen-rich areas like the lungs compared to more oxygen-poor areas like the kidneys. The model allows users to input parameters specific to the organ they're hoping to simulate. That same flexibility also enables to model to be run for individual patients who may have more or less severe versions of the disorder.

To test the potential effectiveness of drugs, the model allows users to input the mode of action by which a drug is presumed to work, information is often gathered during preliminary lab studies. For example, if a drug is designed to boost the amount of healthy hemoglobin in red blood cells, that information can be used by the model to generate the effect on a large population of patient-specific or organ-specific red blood cells.

"Sometimes a drug can be designed to work on one parameter, but ends up having a different effects on other parameters," Karniadakis said. "The model can tell if those effects are synergistic or whether they may negate each other. So the model can give us an idea of the overall effect of the drug."

The researchers are hopeful the model could be useful in identifying promising drug candidates.

"Clinical drug trials are very expensive and the vast majority of them are unsuccessful," Karniadakis said. "The hope here is that we can do in silico trials to screen potential medications before proceeding to a clinical trial."

Amsterdam, NL, August 22, 2019 - Fatigue is a common debilitating symptom in Parkinson's disease (PD). A novel research study has found that fatigue symptoms in PD are associated with small but persistent reductions in diastolic blood pressure (DBP) throughout the day, report scientists in the Journal of Parkinson's Disease.

PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. Fatigue is a disabling non-motor symptom that affects about half of all individuals with PD. A 2015 systematic review on this topic confirmed the absence of high quality evidence supporting any particular PD fatigue treatment.

"The majority of people with PD consider fatigue, defined as diminished energy levels or increased perception of effort that is disproportionate to attempted activities, to be one of their three biggest symptomatic concerns. But despite its high prevalence and disabling nature, we know relatively little about its underlying causes," explained lead investigator Vikas Kotagal, MD, MS, Department of Neurology, University of Michigan and Veterans Affairs Ann Arbor Health System (VAAAHS) and GRECC, Ann Arbor, MI, USA. "Understanding the biological basis for fatigue in PD is a key step towards designing effective treatments. This is an important goal for the field of PD clinical research."

Investigators conducted a cross-sectional study research assessment of 35 people with PD recruited from the Ann Arbor Veterans Affairs Health System, all of whom wore a 24-hour blood pressure monitor to track their blood pressure hourly while they were at home. Researchers asked participants about the presence of fatigue symptoms and grouped them into two categories: those with fatigue and those without.

The data demonstrate study participants with fatigue symptoms had lower mean DBP compared to those without fatigue. The differences were most notable in the morning.

"This is a novel finding that we hope may open the door for new, currently untapped ways to treat fatigue symptoms in PD," commented Dr. Kotagal. "We hope these results will help move us towards better treatments for PD fatigue. If we can design and test treatments that increase DBP without worsening the harmful cardiovascular effects of high systolic blood pressure (SBP), we may be able improve fatigue symptoms in PD. Our data may also have implications on the off-target side effects of some classes of antihypertensive medications when used by patients with PD and fatigue."

SBP, the top number typically given when blood pressure values are presented, is commonly used to describe people's blood pressure because it is a good marker for atherosclerosis and cardiovascular disease. It often gets more attention than DBP, which is typically presented at the bottom. DBP gets comparatively less attention but may better reflect the type of autonomic dysfunction that is common in PD.

Environmental conditions influence our body mass index (BMI) by increasing or decreasing the effect of inherited genetic variations, University of Queensland researchers have discovered.

A team led by Huanwei Wang and Professor Jian Yang from UQ's Institute for Molecular Bioscience found the opposite for human height - that the genetic effects that influence it are very stable from one environment to another.

The discovery could help determine whether, for any particular traits, the effect of a genetic variation is influenced by environmental factors.

"Most human traits, such as height or BMI, are complex because they are influenced by many genetic factors, as well as environmental factors," Professor Yang said.

"But whether the genetic controls of these traits depend on environmental conditions has been elusive - a DNA difference could affect a trait, but is the effect stable across different environments?

"For example, there is a genetic variation known to influence lung function, and the function of this genetic variation is altered significantly by smoking.

"But while the link between smoking and lung function is well-known, how do you discover if a gene variation is affected by an environmental condition if you don't know what that environmental condition is?"

In human populations, it's very difficult to measure all possible environmental factors to which a person has been exposed, so the researchers decided to take a different approach.

Using data from more than 300,000 individuals with a known height and BMI among many other complex traits, the researchers searched for genetic variations associated with the variability of each of those traits.

They found that BMI could differ significantly even for individuals with the same genetic variation, but this wasn't the case for genetic variations associated with height.

"We found a large number of genetic factors for height but their effects do not seem to be sensitive to environmental conditions, while genetic effects on BMI and a few other obesity-related traits seem to be much more sensitive," said Professor Yang.

"Height can be affected by environment for sure, and height can also be affected by genes, but these things seem to be independent."

"It's important to know this because it can enable us to search for elusive environmental factors that might be interfering with the function of a gene."

"It is also informative to design further research to understand why a genetic effect at a particular gene locus is sensitive to environment - knowing the underlying mechanism will be highly important in terms of biology and medical research."

The findings shed new light on the interaction between genomes and environment when it comes to BMI and height, but Professor Yang said the approach could be used much more widely.

AURORA, Colo. (Aug. 22, 2019) - An epidemic of chronic kidney disease that has killed tens of thousands of agricultural workers worldwide, is just one of many ailments poised to strike as a result of climate change, according to researchers at the University of Colorado Anschutz Medical Campus.

"Chronic kidney disease is a sentinel disease in the era of climate change," said Cecilia Sorensen, MD, of the Colorado School of Public Health and the University of Colorado School of Medicine. "But we can learn from this epidemic and choose a wiser path forward."

The article was published today in the New England Journal of Medicine.

Lead author Sorensen and her colleague, Ramon Garcia-Trabanino, MD, said chronic kidney disease of unknown origin or CKDu is now the second leading cause of death in Nicaragua and El Salvador. The death toll from the disease rose 83% in Guatemala over the past decade.

The exact cause of the disease, which hits agricultural workers in hot climates especially hard, remains unknown. It doesn't align with typical chronic kidney disease which is usually associated with diabetes and hypertension.

"What we do know for certain is that CKDu is related to heat exposure and dehydration," Sorensen said, adding that exposure to pesticides, heavy metals, infectious agents and poverty may also play a role.

Sugar cane workers in Central America, who often toil in 104-degree heat in heavy clothing, are often victims of the illness. Sorensen said there is evidence that constant exposure to high temperatures can result in chronic kidney damage.

"They can't say it's too hot, they don't want to go work in the fields," she said. "If they don't work, they don't eat that night."

The disease is also showing up in the U.S. in places like Florida, California and Colorado's San Luis Valley.

And the hotter it gets, Sorensen said, the more likely it will increase along with other diseases.

"When it gets hotter, we see more people in emergency rooms with cardiovascular disease," said Sorensen, who is an emergency department physician at CU Anschutz and a member of the CU Consortium for Climate Change & Health. "We are seeing average global temperatures gradually creep up but one of the biggest risks are heat waves."

She said U.S. public health officials are not prepared for the kinds of heat waves seen in Europe in 2003 that killed over 70,000 people.

"We are way behind the curve on this compared to Europe," she said. "We are also seeing Lyme disease in places we never saw it before because the winters are no longer cold enough to kill off the ticks that carry it."

She said the mosquitos that carry diseases like Zika, dengue fever and Chikungunya are now showing up in the U.S.

"If we are to address both the CKDu and other climate-related diseases, we will have to integrate environmental information into clinical and public health practice and build robust early-warning systems focused on vulnerable communities and climate-sensitive diseases...so we can respond rapidly," she said. "We believe physicians have the opportunity to change the course of the future."

Amsterdam, NL, August 22, 2019 - Cerebral palsy (CP) is one of the most common movement disorders in children. A growing number of caregivers worldwide are caring for children, adolescents and adults with child-onset CP. In this collection of articles in the Journal of Pediatric Rehabilitation Medicine, experts from different disciplines share their experience and summarize new research directed at maintaining and improving function, independence and quality of life in individuals with CP.

This special issue, guest-edited Deborah Gaebler-Spira, MD, Professor of Physical Medicine and Rehabilitation and Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, and Michael M. Green, DO, Associate Professor of Physical Medicine and Rehabilitation, School of Medicine, University of Utah, Salt Lake City, UT, highlights the issues faced by individuals with CP and their carers and brings together new knowledge for the care of children and adults.

CP occurs in about 1.5 to more than 4 per 1,000 live births and continues into adulthood, requiring ongoing rehabilitation. Symptoms include poor coordination, stiff muscles, weak muscles, and there may be problems with vision, hearing, swallowing, speaking, bowel and bladder, and sensation. Children are also at risk of malnutrition due to feeding problems that are common in CP. There is no cure, but supportive treatments, medications and surgery may help. Children with CP may live a full life, depending on the severity.

This collection of articles taps into the expertise of an international group of scientists and discusses multiple aspects of caring for children and adults with CP. The editors hope to promote multidisciplinary thinking and collaboration to improve outcomes.

The articles in this issue cover topics such as:

How to improve scoliosis care

Realistic goal setting

Home exercise programs to improve walking ability in children with diplegia

How to improve walking speed in adults with CP

Prevalence and goal attainment with spinal orthoses for children

Efficacy of prefabricated carbon-composite ankle foot
orthoses

Improving postural symmetry in children with hemiplegia

Safety of intramuscular injections in children with CP

Nutritional care

Classification system for assessing eating and drinking ability

"Children with CP and their families have always been a significant part of the scope of the Journal," explained Dr. Green. "They are frequently seen in trans-multi-interdisciplinary settings with pediatric rehabilitation medicine playing a significant role in their care, for example, spasticity management. The practice of spasticity management continues into adulthood as do other functional interventions."

"We in pediatric rehabilitation medicine have a unique understanding and are in an important position to bridge the lifespan gap that exists in other medical communities," added Dr. Gaebler-Spira. "Our training exposes all of us to adults with disability. Faculty enthusiastically engage with all pediatric rehabilitation medicine residents by teaching and expanding the clinical care for children with CP who are aging into adulthood. Many of us in academic programs have taught the next generation of pediatric rehabilitation providers to consider the needs of adults with CP and continue to work with adults to maintain function and independence."

Recognizing that there is no cure for CP, childhood disability is now an applied science that focuses on function, family, fun, future, fitness and friends. The goal is to increase functionality, improve capabilities and sustain health with respect to locomotion, cognitive development, social interaction and independence. Symptomatic treatment programs involve physical and behavioral therapy, pharmacologic and surgical treatments, mechanical aids and management of associated medical conditions. The creation of subspecialties such as pediatric rehabilitation medicine and neuromuscular medicine now provide specific pathways for training. There is also a clear need among healthcare providers for explicit and clear agreements on how to measure and provide nutritional care for children with CP.

"The ultimate treatment goal is to improve activity, participation and quality of life," concluded the editors. "The challenge ahead is to get all of us working together to improve the lives of the individuals we serve."

Women who have heart attacks experience the same key symptoms as men, quashing one of the reasons given for women receiving unequal care. The British Heart Foundation-funded research puts into question a long-held medical myth that women tend to suffer unusual or 'atypical' heart attack symptoms, and emphasises the need for both sexes to recognise and act on the warning signs.

Incorrectly assuming that women having a heart attack suffer different symptoms to men could lead to misdiagnosis, delayed treatment and less intensive medical interventions being offered. Previous BHF-funded research has shown the resulting differences in care for women were estimated to have contributed to at least 8,200 avoidable deaths in England and Wales in the last decade.

In this latest study, published in the Journal of the American Heart Association, researchers at the University of Edinburgh recorded the symptoms of people attending the Emergency Department (ED) at Edinburgh Royal Infirmary who had a blood test called a troponin test. This test is used when doctors suspect a person is having a heart attack, and measures a protein released by damaged heart cells during a heart attack.

Between 1st June 2013 and 3rd March 2017, doctors in the ED ordered the troponin test for 1,941 people. Of these people, 274 were diagnosed as having a type of heart attack known as an NSTEMI (90 women and 184 men). This is the most common type of heart attack, and occurs when the coronary artery is partially blocked.

Chest pain was the most common symptom for both men and women, with 93 per cent of both sexes reporting this symptom. A similar percentage of men and women reported pain that radiated to their left arm (48 percent of men and 49 per cent of women).

More women had pain that radiated to their jaw or back and women were also more likely to experience nausea in addition to chest pain (33 per cent vs 19 per cent).

Less typical symptoms, such as epigastric pain (heartburn), back pain, or pain that was burning, stabbing or similar to that of indigestion, were more common in men than women (41 per cent in men vs 23 per cent in women).

Previous research has suggested that women and men report different heart attack symptoms. However, the symptoms were often recorded after a heart attack diagnosis was confirmed, which may introduce bias. This study aimed to avoid this by asking an independent research nurse to interview and record the symptoms of all patients arriving at the ED with a possible heart attack before they were given a diagnosis.

The authors now say that further research is needed in larger and more diverse populations to confirm their findings.

Early diagnosis of a heart attack is essential for treatment and survival. BHF-funded research has previously shown that women having a heart attack are up to 50 per cent more likely than men to receive the wrong initial diagnosis and are less likely to get a pre-hospital ECG.

Amy Ferry, cardiology research nurse at the University of Edinburgh and first author, said:

"Our concern is that by incorrectly labelling women as having atypical symptoms, we may be encouraging doctors and nurses not to investigate or start treatment for coronary heart disease in women.

"Both men and women present with an array of symptoms, but our study shows that so-called typical symptoms in women should always be seen as a red flag for a potential heart attack."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said:

"Heart attacks are often seen as a male health issue, but more women die from coronary heart disease than breast cancer in the UK. We need to change this harmful misconception because it is leading to avoidable suffering and loss of life.

"In the UK, three women die of coronary heart disease every hour, many of them due to a heart attack. We know that women tend to wait longer before calling 999 after first experiencing heart attack symptoms. But that delay can dramatically reduce your chance of survival."

Omega-3 fats have little or no effect on risk of Type 2 diabetes according to new research from the University of East Anglia.

Increased consumption of omega 3 fats is widely promoted globally because of a common belief that it will protect against, or even reverse, conditions such as diabetes.

But a systematic review commissioned by the World Health Organization and published today in the British Medical Journal, finds that omega 3 supplements offer no benefit.

Despite over 58,000 participants being randomised into long-term trials, and 4 per cent of those participants developing diabetes, the people who were randomised to consume more long-chain omega-3 fats (fish oils) had the same risk of diabetes diagnosis as the control group who did not take more fish oil.

Blood glucose, insulin and glycated haemoglobin, measures of how well our bodies handle sugars (glucose metabolism) and important measures of diabetes risk, are also similar in people taking and not taking additional fish oils. There was a consistent lack of effect of fish oils (long-chain omega-3 fats) on any of these factors related to diabetes risk.

However, there was some (weak) evidence that when people take high doses of fish oils they may experience worsening glucose metabolism.

Omega 3 is a type of fat. Small amounts are essential for good health and can be found in the food that we eat.

The main types of omega 3 fatty acids are alpha¬linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

ALA is normally found in fats from plant foods, such as nuts and seeds (walnuts and rapeseed are rich sources). EPA and DHA, collectively called long-chain omega 3 fats, are naturally found in fatty fish, such as salmon and fish oils including cod liver oil.

Omega 3 fats are also readily available as over-the-counter supplements and they are widely bought and used.

The research team assessed the effects of long-chain omega-3 fats, ALA, omega-6 and polyunsaturated fatty acids (PUFAs) - taken as supplementary capsules, or via enriched or naturally rich foods.

The systematic review combines the results of 83 randomized controlled trials involving 121,070 people with and without diabetes, all of at least six months duration.

Participants included men and women, some healthy and others with existing diabetes, from North America, South America, Europe, Australia and Asia, in studies published from the 1960s until 2018.

The research assessed the effects of increasing long-chain omega-3 fats, ALA, omega-6 and polyunsaturated fatty acids (PUFAs) on diabetes and glucose metabolism.

Participants were randomly assigned to increase their polyunsaturated fats or to maintain their usual intake for at least six months. There was clearly no effect of increasing long-chain omega-3 fats on diabetes, but there was insufficient information from trials of ALA, omega-6 or total polyunsaturated fats to assess either protective or harmful effects.

The reviewers double-checked their data using sensitivity analyses. For example, they checked that the results did not alter when only the very highest quality trials (those at least risk of bias) were included. They used subgrouping to check whether results differed with different doses of long-chain omega-3 (not finding different effects at different doses except a suggestion of harm at doses over 4.4 grams per day) or by trial duration (there was no suggestion of different effects in longer or shorter trials).

The results show that increasing long-chain omega-3 had little or no effect on diabetes diagnosis or glucose metabolism, but high doses, at levels found in some supplements, could worsen glucose metabolism.

Lead author Dr Lee Hooper, from UEA's Norwich Medical School, said: "Our previous research has shown that long-chain omega 3 supplements, including fish oils, do not protect against conditions such as heart disease, stroke or death. This review shows that they do not prevent or treat diabetes either.

"Omega-3 supplements should not be encouraged for diabetes prevention or treatment. If people do choose to take supplementary fish oil capsules to treat or prevent diabetes, or to reduce levels of triglycerides in their blood, then they should use doses of less than 4.4 grams per day to avoid possible negative outcomes.

"This large systematic review included information from many thousands of people over long periods. Despite all this information, we don't see protective effects.

"The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on diabetes."

Joint first author, Dr Julii Brainard also from Norwich Medical School, said: "Oily fish can be a very nutritious food as part of a balanced diet, but we did not find enough trials that encouraged participants to eat more oily fish to know whether it is useful in preventing diabetes or improving glucose metabolism.

"What we did find is that there is no demonstrable value in ordinary people taking omega 3 oil supplements for the prevention or treatment of diabetes.

"We would also have liked to find out whether taking more omega-3 might be useful in those people with low omega-3 intakes - as giving more omega-3 is more likely to be useful in adults with low intakes. But unfortunately most trials didn't report omega-3 intake levels of participants at the start of the trial, so we still don't know.

"Future trials need to measure and assess baseline omega-3 intakes, and assess effects of eating more oily fish - not just supplements," she added.

Research carried out by The BMJ has found evidence that some trusts are taking action to tackle the NHS pensions crisis ahead of the government's proposed national solution because of concerns about the impact on their workforce.

Frustrated with government inaction, several trusts across England are putting in place their own schemes to help plan for increased demand over the winter.

It follows government changes to pension rules that have led to many senior doctors cutting their working hours or retiring early to avoid punitive tax charges, which the British Medical Association (BMA) has described as "the greatest immediate threat" to medical workforce capacity and patient services.

The situation has increased pressure on an already overstretched workforce. The most recent survey by the BMA earlier this month found that of 6170 respondents, 42% of GPs and 30% of consultants had reduced their working hours because of pension tax charges.

In a bid to make things more flexible, the government recently said it will consult on plans to allow doctors in England and Wales to control how much they pay into their pensions from April 2020.

This is likely to prove more attractive than local schemes because it will allow staff to reduce contributions and therefore their tax burden whilst staying within the NHS scheme - which is not permitted at present.

But some trusts say they can't wait until April and are already allowing doctors to opt out of the NHS scheme and receive employers' contributions in cash, while others are being forced to use agency staff to cover gaps.

The BMJ has learned that, as of July 2019, at least 16 trusts had either set up or were considering some form of salary flexibility scheme. Other trusts told The BMJ thay had run seminars on pensions taxation and enlisted independent financial advisers to speak to staff.

Among the trusts to introduce a local scheme is Dorset County Hospital NHS Foundation Trust which, from September 2018, allowed staff to opt out of the NHS scheme and receive their employer's contributions directly.

Mark Warner, Director of organisational development and workforce at the trust, said in the absence of a national solution, "we felt we had to do something to address the operational concern of people reducing their working capacity."

Warner conceded that Dorset's scheme hasn't had huge pick up from doctors, who have been unsure about quitting the NHS pension scheme. But by offering the option, the trust had raised awareness of the issue and responded proactively.

NHS Providers said that reluctance to quit the NHS pension scheme was common, but warned this may not hold indefinitely, highlighting growing awareness of taxation pitfalls amongst staff.

The BMA says the new proposed flexibilities will provide short-term relief for many doctors, but argues that they do not tackle the core and underlying problem, which lies in wider tax reform.

Finn O'Dwyer-Cunliffe, policy advisor on pensions at NHS Providers, agrees: "We need to see the detail of the consultation but this proposed solution may not wipe out the problem completely."

While Patrick Bloomfield, partner at the pensions consultancy firm Hymans Robertson, said the issue had shown that the UK's "malfunctioning pension tax system" needs to be simplified.

ANN ARBOR, Mich. - A recent study finds that acupressure, a traditional Chinese medicine technique, can improve chronic pain symptoms in the lower back.

"Acupressure is similar to acupuncture, but instead of needles, pressure is applied with a finger, thumb or device to specific points on the body," says Susan Murphy, ScD, OTR, an associate professor of physical medicine and rehabilitation at Michigan Medicine and lead author of the study.

Murphy says that while acupressure has been previously studied -- and found to be beneficial -- in people with cancer-related or osteoarthritis pain, there are few studies that have examined acupressure in people with back pain.

In the study, published in Pain Medicine, the research team randomly assigned 67 participants with chronic low back pain into three groups: relaxing acupressure, stimulating acupressure or usual care.

"Relaxing acupressure is thought to be effective in reducing insomnia, while stimulating acupressure is thought to be effective in fatigue reduction," Murphy says.

Participants in the acupressure groups were trained to administer acupressure on certain points of the body, and spent between 27 and 30 minutes daily, over the course of six weeks, performing the technique.

Participants in the usual care group were asked to continue whatever treatments they were currently receiving from their care providers to manage their back pain and fatigue.

"Compared to the usual care group, we found that people who performed stimulating acupressure experienced pain and fatigue improvement and those that performed relaxing acupressure felt their pain had improved after six weeks," Murphy says.

"We found no differences among the groups in terms of sleep quality or disability after the six weeks."

Potential treatment option

Murphy notes that chronic pain is difficult to manage and people with the condition tend to have additional symptoms such as fatigue, sleep disturbance and depression.

"Better treatments are needed for chronic pain," Murphy says. "Most treatments offered are medications, which have side effects, and in some cases, may increase the risk of abuse and addiction."

She says this study highlights the benefits of a non-pharmacological treatment option that patients could perform easily on their own and see positive results.

"Although larger studies are needed, acupressure may be a useful pain management strategy given that it is low risk, low cost and easy to administer," Murphy says.

"We also recommend additional studies into the different types of acupressure and how they could more specifically be targeted to patients based on their symptoms."