Body

A study of pediatric patients with leukemia demonstrates that they were able to generate T cells against tumor-associated mutations, contradicting previous assumptions that T cells cannot be effectively unleashed on pediatric tumors. Importantly, the findings indicate that pediatric cancers may be more vulnerable to immunotherapies such as checkpoint blockade and other T cell-targeted treatments than previously thought. Tumors often express mutant surface proteins (or neoepitopes) not found in normal cells, which can be recognized and targeted by T cells. Previous research has shown that for solid tumors, only 2% of neoepitopes elicit measurable anti-tumor responses from T cells, suggesting that tumors with a relatively low amount of mutations (such as pediatric tumors) do not provoke typical antitumor responses from the immune system and are thus not suitable candidates for immunotherapy. Seeking insight, Anthony Zamora and colleagues sequenced biopsies from nine pediatric patients with acute lymphoblastic leukemia (ALL), the most common childhood cancer. They identified five to 28 new neoepitopes per patient, and found that the patients harbored T cells that were specific to many of these neoepitopes. The authors observed that the patient T cells responded to 68% of the identified neoepitopes and formed "hierarchies" in how they responded to the mutations. Furthermore, they saw that seven of nine tested patients had T cells that responded to a single mutation called ETV6-RUNX1 that has been linked to more favorable clinical outcomes.

Orthopaedic surgeons are the third-highest physician prescribers of opioids, writing more than 6 million prescriptions a year. Because over-dispensing of opioids is a factor contributing to the ongoing opioid epidemic, researchers at Johns Hopkins surveyed orthopaedic providers to better understand what drives their prescribing practices and to identify gaps in knowledge and potentially worrisome trends. In their survey of 127 orthopaedic providers in the Baltimore area, the Johns Hopkins researchers found that respondents frequently recommended prescribing a nine-day supply of around-the-clock oxycodone doses following commonly performed orthopaedic surgeries. The researchers also found that risk factors that might normally warrant prescribing fewer opioids, such as a history of drug misuse or depression, often did not diminish hypothetical prescribing rates.

The researchers published their findings on June 22 in the Journal of Opioid Management.

In the survey, researchers gauged responses to six scenarios routinely encountered by orthopaedic surgeons. They found that although increased experience was associated with decreased prescribing, 95% of respondents recommended prescribing at least 55 oxycodone pills following five of the six surgeries described. That amounts to a nine-day supply of medication, more than current recommendations from the Centers for Disease Control (issued since the survey was conducted) that no more than a three- to seven-day supply routinely be prescribed. In addition, comparing this result with recent studies looking at opioid use after orthopaedic surgery suggests that this number of doses was more than what is usually required to adequately treat post-operative pain.

The study also found that 62% of respondents reported that they do not routinely use their state-sponsored electronic prescription drug-monitoring program, which can help flag when patients go "doctor shopping" for a new source of pills. Finally, 79% of respondents reported that they do not provide opioid disposal instructions to their patients, which researchers are concerned can lead to unused pills remaining in homes and potentially getting into the wrong hands.

"Our findings show that there are clear knowledge gaps among orthopaedic surgeons for best practices for prescribing opioids that can and should be addressed," says lead author Constance Monitto, M.D., assistant professor of anesthesiology and critical care medicine and director of the pediatric acute pain service. "Evidence-based guidelines for opioid prescribing for specific procedures are also needed to curb overprescribing while still adequately treating pain."

Monitto notes that since the time the study was performed, Johns Hopkins has created a committee to help establish prescribing guidelines specifically for routine surgical procedures, and an additional group is developing educational materials for patients on safe handling and disposal of medications. She says other hospitals and health care centers should follow suit in order to curb overprescribing and decrease the risk of patient harm.

Despite the fact that many women who suffer migraines find that the number and severity of these severe headaches decrease during pregnancy, migraines are now being linked to elevated blood pressure, abortions, caesareans, preterm births and babies with low birth weight.

This is documented by an extensive register-based study recently published in the scientific journal Headache and carried out at the Department of Clinical Epidemiology at Aarhus University and Aarhus University Hospital, Denmark.

"The study shows that pregnant women with migraine more often have complications in connection with their pregnancy and childbirth than women who don't suffer from migraine. Newborn babies whose mothers suffered from migraine during pregnancy also have an increased risk of complications such as respiratory distress and febrile seizures," says Nils Skajaa, BSc, who is the study's lead author.
He is employed as a researcher at the Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital.

The researchers behind the study used the Danish health registers to identify more than 22,000 pregnant women with migraine who were in contact with a hospital as a result of their migraine or had received at least two prescriptions for migraine medication. The group was compared with an approximately ten times larger group of pregnant women without known migraine.

One finding in the study is that the risk of caesarean sections is between 15-25 per cent higher for pregnant women with migraine compared with pregnant women without migraine. Around twenty per cent of all births in Denmark are by caesarean section.

Researchers have also used the same data to deduce that migraine medication possibly prevents some of the complications. However, the results must be interpreted with caution, as Nils Skajaa explains:

"The study was not specifically designed to examine this aspect. However, we show that the risk of complications generally was lower for pregnant women with migraine who took medication when compared with the pregnant women with migraines who were not treated. This also indicates that the migraine medication isn't the cause of the complications, but rather the migraine itself. This is important knowledge for pregnant women with migraines," says Nils Skajaa.

Migraines are relatively common and affect twice as many women as men. The actual cause remains unknown, but previous research suggests that migraines may be triggered by stress, fatigue, or hormonal changes such as pregnancy.

"Paradoxically, women of childbearing age are particularly hard hit by migraines. Although experience shows that migraines become milder during pregnancy, this study emphasises that the healthcare service should be particularly aware of pregnant women with migraine," says Nils Skajaa.

CRISPR-Cas9: First in vivo proof-of-concept in Steinert's myotonic dystrophy, a neuromuscular disease

Ana Buj Bello's team, a researcher in an Inserm unit at Genethon, the AFM-Telethon laboratory, has made the proof-of-concept of a CRISPR-Cas9 approach in a mouse model of Steinert's myotonic dystrophy, the most common neuromuscular disease in adults. Indeed, thanks to this genome editing approach, the expanded CTG triplet repeat in the DMPK gene, which is responsible for the disease, was "cut" and removed from the gene, and the number of toxic RNA aggregates was decreased in the muscle cells of the tested models. Based on these encouraging results, published in the June 5 issue of Molecular Therapy, the researchers are currently investigating whole body treatment.

Steinert's myotonic dystrophy (DM1) is the most common form of adult muscular dystrophies. With a genetic origin, its prevalence is estimated at 1 in 8,000 persons, and is mainly characterized by difficulties in relaxing after contraction (myotonia) and a progressive muscle weakness. The disease is due to mutations in the DMPK gene, in particular, to an increase in the number of repeats of a small 3-nucleotide DNA sequence, a CTG triplet, located in the DMPK gene. This results in the accumulation of mutated DMPK RNA in the cell nucleus, leading to alterations in cellular functions. There is currently no cure for this neuromuscular disease.

In this study, Ana Buj Bello's team, in collaboration with Denis Furling's team at the Institute of Myology and Genevieve Gourdon's team at the Imagine Institute, have developed and evaluated a gene therapy approach using the CRISPR-Cas9 molecular scissors in cellular and in vivo mouse (DMSXL) models of the disease:

In the cellular model : The team has identified guide RNAs that target DNA sequences around the CTG triplet region of the DMPK gene, and demonstrated that the Cas9 protein removes this part of the genome, resulting in the disappearance of nuclear toxic RNA aggregates in treated cells.

In the mouse model : The team has used the same technology in vivo and administrated intramuscularly gene therapy vectors (AAV9) that carry Cas9 and guide RNAs targeting the DMPK gene. Few weeks after injection, a decrease in toxic RNA aggregates was observed in the nuclei of muscle cells of diseased mice.

"After several years of work, we have been able to demonstrate that the CRISPR-Cas9 system works in skeletal muscle for Steinert's disease. These results represent a very encouraging first step, and we now plan to optimize this approach to correct the entire musculature and other tissues affected by the disease", highlights Ana Buj-Bello, lead author of the work.

The benefits of living in a walkable neighbourhood could be diminished by increased exposure to traffic-related air pollution, suggests a study led by St. Michael's Hospital and ICES, a non-profit research institute that uses population-based health information to produce knowledge on a broad range of health care issues.

The research, published today in Environment International, and based on nearly 2.5 million adults from 15 Ontario municipalities, challenges the notion that living in walkable neighbourhoods always improves the overall health and well-being of Canadians.

Walkability reflects how well neighborhoods afford opportunities for individuals to walk while performing daily tasks like grocery shopping, running errands, or commuting to work.

"Previous research has shown that individuals living in more walkable neighborhoods are more physically active, with downstream health benefits like lower rates of overweight and obesity, hypertension and diabetes," said study co-lead Dr. Gillian Booth, a scientist at St. Michael's Hospital's MAP Centre for Urban Health Solutions and ICES. "But our findings confirm that walkability and air pollution are highly intertwined, potentially diminishing any health benefits derived from living in walkable, urban communities."

The research team found that living in unwalkable neighbourhoods was associated with a higher likelihood of having diabetes or hypertension than living in the most walkable communities. But, any observed benefit for those living in walkable areas appeared to decrease -- or in some cases, disappear -- as the level of air pollution increased.

"Individuals living in highly walkable neighbourhoods tend to be more likely to choose active forms of transportation, like walking or bicycling, as an alternative to driving," said Nicholas Howell, a recent PhD graduate in the St. Michael's Li Ka Shing Knowledge Institute and co-lead of the research. "So they may be more exposed to air pollution based simply on the amount of time they spend outside."

The researchers said these results suggest that policies aimed at encouraging the development of walkable neighbourhoods should consider strategies to mitigate residents' exposure to air pollution.

"Initiatives to create walkable communities while decreasing sources of car pollution may have promise to reap even greater health benefits and have stronger impact on the health of Canadians," said Howell.

Researchers used participant data from the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort - a population-based cohort drawn from databases including nearly all adults living in Ontario.

A new study soon to appear in the Journal of Public Health suggests that air pollution and living in apartment buildings may be associated with an increased risk for dangerous conditions like heart disease, stroke, and type 2 diabetes.

Cardiovascular diseases are a leading cause of death in developing countries. Hypertension and metabolic syndrome are important causes of cardiovascular diseases. Metabolic syndrome is further associated with abdominal obesity, elevated blood pressure, and higher blood glucose levels. These conditions are associated with a higher risk for various health problems. The causes of these disorders are complex and are related to genetic factors, lifestyle, diet, and environmental factors including traffic air pollution, traffic noise, residential housing, and neighborhood quality.

Researchers here investigated the associations between a long-term exposure to ambient air pollution and residential distance to green spaces and major roads with the development of hypertension and some components of metabolic syndrome. These associations were assessed among people living in private houses or multi-story houses in Kaunas City, a city of 280,000 and the second largest city of Lithuania.

In the present study, researchers investigated the association between a long-term exposure to ambient air pollution and the residential distance to green spaces and major roads with the development of hypertension and some components of metabolic syndrome. These components included: a high triglyceride level, reduced high-density lipoprotein cholesterol, higher blood glucose, and obesity. The associations were assessed among people who lived in either private or multifamily houses.

The results indicate that air pollution levels above the median are associated with a higher risk of reduced high density lipoprotein. Traffic-related exposure was associated with the incidence of hypertension, higher triglyceride level and reduced high-density lipoprotein cholesterol. However, the negative impact of traffic air pollutants was observed only in the participants who lived in multifamily buildings.

Since there is more traffic near the multifamily apartment buildings, this may be associated with the incidence of hypertension as well. In addition, a built-up environment, high residential density, street traffic and its configurations are further factors associated with social interactions and supportive relationships, which could also impact cardiovascular health.

The greenness, size, and type (activity) of the available open public spaces were observed to be inversely related to the risk factors assessed. Investigators have additionally found positive effects of the natural environment, and have emphasized the positive impact of such spaces on cardiovascular health.

"Our research results enable us to say that we should regulate as much as possible the living space for one person in multifamily houses, improve the noise insulation of apartments, and promote the development of green spaces in multifamily houses" said the study's lead author, Agnė Brazienė.

NEW YORK, June 25, 2019 - In the 1860s, French physician Paul Broca published his findings that the brain's speech production center was located in the left hemisphere. Though scientists have largely accepted since then that the left half of the brain dominates language processing, the reasons behind this lateralization have remained unclear.

"The lateralization of language processing in the auditory cortical areas of the brain has been known for over 150 years, but the function, neural mechanisms, and development of this hemispheric specialization are still unknown," said Hysell V. Oviedo, a biology professor with The Graduate Center, CUNY and the City College of New York.

A new study from Oviedo's lab, published in Nature Communications, makes headway into this mystery. Using the mouse as a model system, the researchers observed different specializations between the left and right auditory processing centers of the brain, and found differences in their wiring diagrams that may explain their distinct speech processing functions.

In addition to answering long-standing questions in neuroscience and language processing, the results of Oviedo's study could someday lead to a better understanding of certain mental health problems. Autism spectrum disorder has been linked to a failure of lateralized language processing to develop between the two halves of the brain. And abnormal lateralization is a risk factor for auditory hallucinations in schizophrenia.

One common feature of mouse vocalizations is syllables with downward jumps in pitch. The left auditory cortex in the mouse showed greater activation in response to these tone sequences, whereas the right auditory cortex appeared to be more of a generalist, responding to any tone sequence. Specializations to detect specific tone sequences prevalent in vocalizations could underlie the left auditory center's dominance in processing the content or meaning of speech. While the right auditory center's generalist scheme could underlie its dominance in processing the intonation or prosody of speech.

Notably, the specialized differences between the left and right sides are not innate. Rather, Oviedo says, the differences between their circuitry depend on the acoustic environment in which the mouse was raised.

"Our discovery of the differences in the wiring diagram provides the opportunity to study the molecular phenotypes that shape the development of vocalization processing and how it goes awry in neurodevelopmental communication disorders," Oviedo said.

Through a battery of experiments such as 3D whole-brain imaging, electrophysiology, and optogenetics, the researchers analyzed properties including synaptic connectivity, axonal projections and development of both hemispheres. "Our study is the first to show that there are significant differences in the wiring diagram of the language centers in the brain that could underlie their distinct speech processing capabilities," Oviedo said.

A new way of detecting liver disease decades before it can become fatal has been developed by a team of scientists at the University of Dundee and NHS Tayside.

It comes as clinicians warn of a `ticking time bomb' of alcohol-related and obesity-related liver diseases.

Liver disease, which is notoriously asymptomatic, has become the second most common cause of death in under 65 year-olds in the UK. Unlike other common causes of death which have begun to decline in recent years, the age-standardised mortality rates for liver disease have risen by nearly 600% since the 1970s.

Liver function is routinely investigated by testing blood samples requested by GPs. Results commonly show abnormal liver function but this is often under-investigated due to the many different and complex reasons for an abnormal result. This misses the opportunity to diagnose and treat liver disease at an early stage.

Professor John Dillion, Consultant gastroenterologist and hepatologist, said, "Around 800 people die from liver disease every year in Scotland and the wards are full of liver failure in ways that they just weren't two decades ago. Liver disease is a silent killer, it creeps up on you. So it is crucial that we find a way to detect it earlier and switch off this ticking time bomb."

Professor Dillon and consultant in biochemical medicine Dr Ellie Dow worked with colleagues from the University of Dundee and NHS Tayside to develop the intelligent liver function tests (iLFTs) using the automated Blood Sciences laboratory infrastructure at Ninewells Hospital.

Using advances in laboratory technology, the team created the new iLFTs which see more tests automatically carried out on a patient's blood sample if there is a suspected liver disorder or abnormal results with no clear explanation.

Initial results from the trial showed a 44% increase in diagnosis of liver disease, giving patients earlier access to treatment. Professor Dillon said, "In looking at a large set of patient data from Tayside we noticed abnormal liver function tests popping up that were not fully investigated.

"All too often we were seeing patients dying of liver failure who had abnormal Liver Function Tests recorded years before when something could have been done. This stopped us in our tracks. We asked ourselves if these had been detected earlier, what difference could it have made?

"By applying variables to the existing IT systems in the lab, we were able to develop a system that detects the early warning signs of liver disease and which can then give GPs the tools they need to make a solid diagnosis and begin treatment plans. More importantly, our modification allows us to immediately differentiate between alcoholic or non-alcoholic fatty liver disease and the more rare diseases such as autoimmune liver diseases, Hepatitis C or metabolic diseases, meaning those who need immediate assistance receive it faster."

Since being launched in NHS Tayside in June last year more than 2,500 patients have been tested, with 30% of these showing abnormal results.

Professor Dillion added, "We've been predicting that a liver failure epidemic has been coming but now we are seeing hard-evidence that it is already here. We hope that, with continued tests, people drinking too much or eating high-fructose sugars can make the lifestyle changes now that will reduce the number of those coming into hospital with fatal liver failure in the years to come."

The results of the team's work have been published in the Journal of Hepatology this month.

iLFT tests have now been made standard practice across NHS Tayside and the Scottish Government's Modern Outpatient Programme is considering the opportunities this might present, with work underway to determine whether there is potential to roll this out more widely across Scotland.

Health Secretary Jeane Freeman said, "This is an innovative piece of work that is using technology to bring a real improvement to patients' outcomes. Early detection is absolutely key to successful treatment. I would like to congratulate the team at the University of Dundee and NHS Tayside for their valuable work in this area."

Dr Andrew Fraser, Clinical lead for roll out of iLFT from the Scottish Government's Modernising Outpatients Directive, said, "For too long have we seen the rise in patients presenting with advanced liver disease which could have been picked up on routine tests at a much earlier stage. The development by the Dundee team will help to identify those at an early stage where directed intervention can prevent progression to end-stage liver disease. This is only available to patients in Tayside at present and we strongly recommend other health boards adopt it as standard practice across Scotland."

The iLFT project was recognised with several prestigious awards in May including: Innovation in Practice Gold award at NHS Tayside STAR Awards 2019; Innovation award at Royal College of Physicians' Excellence in Patient Care Awards 2019; 2019 UNIVANTS of Healthcare Excellence Award; Frontline Gastroenterology Prize for the 'Best patient benefit in gastroenterology and hepatology'; Innovation Award at the Royal College of Pathology Excellence Awards 2019; and Highly Commended in the Digital Innovation category of the BMJ Awards 2019.

People with chronic diseases like arthritis, diabetes and heart disease may one day forego the daily regimen of pills and, instead, receive a scheduled dosage of medication through a grape-sized implant that is remotely controlled.

Researchers from Houston Methodist successfully delivered continuous, predetermined dosages of two chronic disease medications using a nanochannel delivery system (nDS) that they remotely controlled using Bluetooth technology. The nDS device provides controlled release of drugs without the use of pumps, valves or a power supply for possibly up to year without a refill for some patients. This technology will be tested in space next year.

A proof-of-concept paper recently published in Lab on a Chip (online June 25) explains how the Houston Methodist nanomedicine researchers accomplished long-term delivery of drugs for rheumatoid arthritis and high blood pressure, medications that are often administered at specific times of the day or at varying dosages based on patient needs.

"We see this universal drug implant as part of the future of health care innovation. Some chronic disease drugs have the greatest benefit of delivery during overnight hours when it's inconvenient for patients to take oral medication. This device could vastly improve their disease management and prevent them from missing doses, simply with a medical professional overseeing their treatment remotely," said Alessandro Grattoni, Ph.D., corresponding author and chair of the department of nanomedicine at Houston Methodist Research Institute.

Grattoni and the Houston Methodist researchers have worked on implantable nanochannel delivery systems to regulate the delivery of a variety of therapies for medical issues ranging from HIV-prevention to cancer. As basic research progresses with the remote-controlled device, the Houston Methodist technology is planned for extreme remote communication testing on the International Space Station in 2020. The team hopes that one day the system will be widely available to clinicians to treat patients remotely via telemedicine. This could provide both an improvement in the patients' quality of life and a reduction of cost to the health care system.

The battery-powered implant contains a microchip that is Bluetooth enabled and relies on wireless communication. To prove the technology worked as planned, the microchip was programmed for three different drug release settings - standard, decreased and increased. With each setting, a specific voltage was applied to a silicon nanochannel within the implant to control drug release.

Current drug delivery devices, such as pain or insulin implants, rely on pumping mechanisms or external ports and typically need refills every couple of months. The Houston Methodist device is implanted under the skin and uses a nanofluidic membrane made with similar technology used in the silicon semiconductor industry. The drug dosage and schedule can be tailored to each patient, and the implant delivers the drugs for many months, even a year, before refills are needed.

According to the CDC, chronic diseases are among the most common, costly and preventable of all medical problems.

ANN ARBOR, Mich. - Having diabetes is a risk factor for many other health conditions, including stroke.

"Every 40 seconds an American has a stroke," says Frederick Korley, M.D., Ph.D., an assistant professor of emergency medicine at Michigan Medicine. "To be successful at preventing strokes from occurring, we first need to accurately identify those who are likely to have a stroke so we can target stroke prevention therapies to the correct at-risk people."

Korley is the author of a new study, published in Stroke, that measured levels of a blood protein in patients with diabetes, who had not previously had a stroke, to predict their risk of experiencing a stroke in the future.

"We hypothesized that before an individual has a stroke, they often have 'small strokes' that do not cause clinical symptoms," says Korley, also a member of the Michigan Center for Integrative Research in Critical Care.

"However, these small strokes may result in the release of proteins that are associated with brain cell death, and these proteins can be measured in blood," he says. "One of these proteins is neurofilament light chain (NfL), the focus in our study."

Blood levels of NfL

Korley and team examined blood samples from 113 diabetic patients who were stroke-free at the time of study enrollment but developed a stroke during a seven-year follow-up period, and 250 diabetic patients who were stroke-free at study enrollment and did not develop a stroke during the seven-year follow-up period.

The research team found that levels of NfL in the blood appeared to contribute to stroke risk.

"We found that those who developed a stroke had blood levels of NfL that were about 43 percent higher than those who did not develop a stroke," Korley says. "And those with the highest NfL levels -- the top 25 percent of our study participants -- were 10 times more likely to develop a stroke during the seven-year follow-up period, than those with low levels of NfL -- the bottom 25 percent of our study participants."

While the results confirmed the research team's hypothesis, Korley says he was a bit surprised by the results.

"The strength of the association between the blood test and stroke was larger than we were expecting," he says.

Korley says that the research team also found that adding NfL levels to the current method of predicting stroke, the Framingham Stroke Risk Score, increased the method's accuracy.

"The Framingham Stroke Risk Score looks at stroke risk factors in a patient and predicts 10-year probability of a stroke occurring," he says. "The score currently includes factors such as diabetes, current smoking status and blood pressure. When we added NfL levels as a risk factor, the score appeared to become even more accurate in predicting stroke."

Future use

Korley notes that this is the first study reporting the usefulness of this blood test in predicting stroke occurrence, and additional studies are needed to confirm the team's findings.

"Our test also looked specifically at patients with diabetes, and further studies will need to take place to determine how well this test will work in nondiabetics and the general population," he says.

But, Korley hopes those additional studies can happen soon.

"As an emergency physician, I see patients after they have experienced a stroke, and for some patients, the options for treating them at that time point are limited," he says.

"If our findings hold true in other study populations, physicians could use this test to monitor patients and target stroke prevention treatments to the right at-risk people to hopefully help them avoid a stroke from ever happening."

A Finnish study demonstrates that as little as half an hour of light exercise per week effectively protects against subarachnoid haemorrhage, the most lethal disorder of the cerebral circulation.

Among disorders of the cerebral circulation, subarachnoid haemorrhage (SAH) is the most lethal kind, with as many as half of those affected dying within three months. As the related mortality rate is high, a feverish search for predisposing factors has been underway across the globe for the past few decades. Previously, smoking and high blood pressure have been observed to heighten the risk of an SAH haemorrhage, but research evidence on the effects of exercise has remained scarce.

In a Finnish follow-up study published in the distinguished Scientific Reports journal, the effects of exercise on SAH risk were investigated in a cohort of roughly 70,000 Finns gained from the FINRISK population survey. The findings indicate that as little as half an hour of light exercise per week reduces the risk of SAH by approximately 5%, with the benefit increasing proportionally to the amount of exercise. This can be achieved, for example, by walking, cycling or, say, skiing to work.

"Even moderate physical exercise, such as a 30-minute walk or bike ride four days a week reduces the risk of SAH by roughly 20%, regardless of age and gender," says physician Joni Lindbohm, the principal author of the research article.

"As such, the finding did not really come as a surprise, as exercise is known to work well in preventing many other cardiovascular diseases. However, the extent and comprehensive nature of the benefit among various groups of people was a positive surprise."

The study also demonstrated the favourable effect of increased exercise in connection with smoking and high blood pressure, the other SAH risk factors. For smokers in particular, exercise reduces the risk as much as twice the amount applicable to the rest of the population.

"However, what must not be overlooked is the fact that smoking remains the number one risk factor for SAH and that quitting smoking is the principal way of preventing the appearance of the disorder," Lindbohm notes.

Most SAH haemorrhages are the result of ruptured cerebral aneurysms, causing blood to flow from the largest cerebral arteries into the space between meninges, the membranes surrounding the brain, which increases intracranial pressure and reduces cerebral circulation.

"Even with no accurate scientific evidence of the biological mechanism of action produced by exercise in terms of SAH, the reduced risk is most likely connected with a reduction in a systemic inflammatory state, which also affects the walls of cerebral arteries," neurosurgeon Miikka Korja explains.

According to Lindbohm and Korja, key to minimising the risk of SAH is quitting smoking, balancing one's blood pressure and exercising regularly.

Worldwide, about 44 million people are living with Alzheimer's disease (AD) or a related form of dementia. Although 82 percent of seniors in the United States say it's important to have their thinking or memory checked, only 16 percent say they receive regular cognitive assessments.

Many traditional memory assessment tools are widely available to health professionals, though deficiencies in screening and detection accuracy and reliability remain prevalent. But even with the increasingly favorable instrument MemTrax, a very simple online memory test using images recognition, the clinical efficacy of this new approach as a memory function screening tool has not been sufficiently demonstrated or validated. In practice, there are numerous integrated and complex factors to consider in interpreting memory evaluation test results, which presents a real challenge for clinicians. All these factors stand as a collective barrier to suitably addressing the growing and widespread prevalence of AD and those affected by the disease.

Could artificial intelligence be the solution for testing and managing this complex human health condition? A team of researchers at Florida Atlantic University's College of Engineering and Computer Science, SIVOTEC Analytics, HAPPYneuron, MemTrax, and Stanford University School of Medicine, think so, and put their theory to the test.

The researchers employed a novel application of supervised machine learning and predictive modeling to demonstrate and validate the cross-sectional utility of MemTrax as a clinical decision support screening tool for assessing cognitive impairment.

Results of the study, published in the Journal of Alzheimer's Disease, introduce supervised machine learning as a modern approach and new value-added complementary tool in cognitive brain health assessment and related patient care and management.

Findings demonstrate the potential valid clinical utility of MemTrax, administered as part of the online Continuous Recognition Tasks (M-CRT) test, in screening for variations in cognitive brain health. Notably, a comparison of MemTrax to the recognized and widely utilized Montreal Cognitive Assessment Estimation of mild cognitive impairment underscores the power and potential of this new online tool and approach in evaluating short-term memory in diagnostic support for cognitive screening and assessment with a variety of clinical conditions and impairments including dementia.

"Machine learning has an inherent capacity to reveal meaningful patterns and insights from a large, complex inter-dependent array of clinical determinants and the ability to continue to 'learn' from ongoing utility of practical predictive models," said Taghi Khoshgoftaar, Ph.D., co-author and Motorola Professor in FAU's Department of Computer and Electrical Engineering and Computer Science. "Seamless use and real-time interpretation will enhance case management and patient care through innovative technology and practical and readily usable integrated clinical applications that could be developed into a hand-held device and app."

For the study, the researchers used an existing dataset (18,395) from HAPPYneuron. They examined answers to general health screening questions (addressing memory, sleep quality, medications, and medical conditions affecting thinking), demographic information, and test results from a sample of adults who took the MemTrax (M-CRT) test for episodic-memory screening. MemTrax performance and participant features were used as independent attributes: true positive/negative, percent responses/correct, response time, age, sex, and recent alcohol consumption. For predictive modeling, they used demographic information and test scores to predict binary classification of the health-related questions (yes/no) and general health status (healthy/unhealthy), based on the screening questions.

"Findings from our study provide an important step in advancing the approach for clinically managing a very complex condition like Alzheimer's disease," said Michael F. Bergeron, Ph.D., senior author and senior vice president of development and applications, SIVOTEC Analytics. "By analyzing a wide array of attributes across multiple domains of the human system and functional behaviors of brain health, informed and strategically directed advanced data mining, supervised machine learning, and robust analytics can be integral, and in fact necessary, for health care providers to detect and anticipate further progression in this disease and myriad other aspects of cognitive impairment."

AD is the sixth leading cause of death in the United States, affecting 5.8 million Americans. According to the Alzheimer's Association, this number is projected to rise to 14 million by 2050. In 2019, AD and other dementias will cost the nation $290 billion. By 2050, these costs could rise as high as $1.1 trillion.

"With its widespread prevalence and escalating incidence and public health burden, it is imperative to ensure that the tools clinicians use for testing and managing Alzheimer's disease and other related cognitive conditions are optimal," said Stella Batalama, Ph.D., dean of FAU's College of Engineering and Computer Science. "Results from this important study provide new insights and discovery that has set the stage for future impactful and significant research."

State policies requiring children to attend additional years of school may result in a reduced risk for heart disease and improvements in several cardiovascular risk factors in adulthood, according to a study by researchers at UC San Francisco and Stanford University.

In the study, the researchers conducted a natural experiment by evaluating state compulsory schooling laws, which legislate the number of years children must attend school. From two large, national surveys conducted from 1971 to 2012, they identified more than 75,000 people born from 1900 to 1950, when states required children to attend school between 0 and 12 years. They then used U.S. Census data on a group of similar individuals to predict the number of years of required schooling for each individual, based on their year and state of birth.

Overall, about a third of the study participants did not graduate from high school. While 34.5 percent reported heart disease, the researchers found that each year of additional compulsory schooling through high school was associated with a 2.5 percent reduction in occurrence. They also noted improvements in several cardiovascular risk factors with each additional year, including reductions of more than 3 percent in smoking and nearly 5 percent in depression.

"For clinicians and health systems struggling to address disparities in heart disease between the rich and the poor, our findings suggest that cross-sectoral interventions to address social factors like education are important," said lead author Rita Hamad, MD, PhD, assistant professor of family and community medicine in the Philip R. Lee Institute for Health Policy Studies. "As a society, we should be thinking about investing in social policies to improve overall health and reduce health care costs."

The study, published online June 25, 2019, in PLOS Medicine, provides some of the first evidence of the effects of education policies on heart disease in the United States.

The 2019 guidelines from the American College of Cardiology and the American Heart Association have suggested using patients' social factors in clinical prediction tools for heart disease, since education is often a stronger predictor than traditional biomedical risk factors like cholesterol and diabetes. The U.S. Department of Health and Human Services also has proposed that patients' educational attainment be used as an input in determining physician payments for performance, to encourage physicians to care for more disadvantaged patients. Hamad said this type of data could inform those efforts.

While more education also was associated with improved high-density lipoprotein (HDL), or "good" cholesterol, the researchers found that more education also was associated with higher body-mass index (BMI) and total cholesterol. A possible explanation is that high-income people born between 1900-1950 tended to eat richer diets, they said. By contrast, higher BMI today tends to be associated more with low income, due to the inability to afford healthy food.

"Overall, people with more education may have reduced heart disease because they have higher incomes, allowing them to afford better food and health care," Hamad said. "Or, it may be that they have more resources and therefore less stress, which has been previously linked with heart disease."

The researchers are examining how these same policies affect health care costs and whether the policies reduce racial disparities in heart disease.

WEST LAFAYETTE, Ind. -- For advanced stages of head and neck cancer, one of the best treatments is so aggressive that it could bring tooth decay, speech loss, constant nausea or all of the above.

That's because the treatment combines two therapies - chemotherapy and radiation - which means double the cancer-killing power, but also double the side effects. A large proportion of the 63,000 Americans diagnosed with head and neck cancer each year are ineligible for this treatment because they are too old or too sick, but most don't know they have the cancer until after the age of 50.

Purdue University researchers in collaboration with the Indiana University School of Medicine have created a new chemoradiotherapy formulation that they predict should be even more effective than what is available commercially. The formulation shouldn't produce side effects because all its toxins stay within tumors, rather than leaking into the bloodstream and harming the whole body.

The study, which appears in a recent issue of the Journal of Controlled Release, shows that the formulation is successful in cancer cell culture experiments, in-vivo animal models and mathematical simulations of patient data. Next, the researchers intend to test the formulation in dogs that naturally have head and neck cancer.

"All previous commercial formulations are not optimized for releasing directly at the tumor under radiation," said You-Yeon Won, a professor of chemical engineering at Purdue, whose lab focuses on improving drug and gene delivery in the body.

"Our formulation has more control and could also be applied to any type of solid tumor, such as those in the breast, prostate, lungs or liver," he said.

The formulation, designed to be delivered to a tumor via a long syringe needle, is a capsule containing a chemotherapy drug and nanoparticles - tiny compounds that sensitize cancer cells to radiation, making them easier to kill.

Once injected into the body and activated by X-ray radiation, the nanoparticles produce UV light, cracking open the capsule coating so that the chemotherapy drug rapidly releases to a tumor. The coating is biocompatible and approved by the FDA.

Here's the edge: The drug stays in the tumor at least a month - far longer than the minimal therapeutic threshold - and its concentration outside of the tumor stays well below a toxic threshold. Since the drug toxins aren't leaking out of the tumor much, they aren't damaging other cells, which means that there would be virtually no side effects.

The radiation also isn't tearing through other tissue, causing problems like tooth decay, because the nanoparticles keep it targeted at cancer cells.

"We've developed the first-in-kind chemoradiotherapy formulation that can release drugs in response to X-ray radiation. Only under radiation does it start releasing the drug," Won said.

New research from the University of Alabama at Birmingham provides evidence, for the first time, for physicians to continue using the spirometry criteria set by major respiratory societies for the diagnosis of airflow obstruction and chronic obstructive pulmonary disease.

Published in the Journal of the American Medical Association, Surya Bhatt, M.D., associate professor in the Division of Pulmonary, Allergy and Critical Care Medicine and medical director of the UAB Pulmonary Function and Exercise Physiology Lab, says there is much confusion and debate in the medical community on what are the best spirometry criteria to use for diagnosing COPD.

Currently, major respiratory society guidelines recommend diagnosing airflow obstruction when the ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity (FVC) is less than a fixed threshold of 0.70. This means that, during a forced exhalation following a maximal inhalation, a normal individual should be able to blow out at least 70 percent of their lung size or vital capacity in the first second. However, there is no rigorous, population-based evidence to support the threshold of 0.70, which was set by expert opinion as the optimal FEV1/FVC threshold for defining clinically significant airflow obstruction, according to the published research.

"A diagnosis of COPD needs confirmation by demonstrating obstruction to airflow using spirometry," Bhatt said. "The currently used criteria are based on expert opinion, and until these results were published, there was not enough evidence to support their use."

The multisite team, led by researchers from UAB and the University of Columbia, analyzed data from a large, multi-ethnic sample of 24,207 adults in the United States, and found that the currently used threshold of 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different from -- or was more accurate than -- other fixed thresholds. The 0.70 threshold was also more accurate than other thresholds that define normal lung function and are derived from reference populations. These results support the continued use of FEV1/FVC

Cigarette smoking is the primary cause of COPD in the United States, but air pollutants at home (secondhand smoke and some heating fuels), at work (dusts, gases and fumes) and for those with genetic predisposition also can cause COPD. COPD makes breathing difficult for the estimated 14 million Americans who have this disease. Millions more suffer from COPD, but have not been diagnosed. Although there is no cure, it can be treated.

"The ongoing disagreement between experts on the best spirometry criteria to diagnose airflow obstruction has resulted in a lack of clarity for clinicians," Bhatt said. "Using a simple standard threshold has the potential to improve the diagnosis and treatment of this common disease."

According to the Centers for Disease Control and Prevention, Alabama has one of the highest rates of COPD. About 9.6 percent of Alabama residents surveyed in 2011 reported having been told by a health care professional that they have COPD. "The symptoms of COPD are often non-specific, and an accurate diagnosis will determine who gets appropriately treated, and is also important for avoiding unnecessary therapies," Bhatt said.