Body

MISSOULA - University of Montana Assistant Professor Richard Willy is the lead author on a paper that offers new guidelines for treating patellofemoral pain, often known as "runner's knee."

Patellofemoral pain (PFP) affects one in four of the general population every year, with women reporting PFP twice as often as men. The pain presents at the front of the knee, under and around the kneecap. Willy's paper finds that exercise therapy - namely hip and knee strengthening treatments prescribed by a physical therapist - is the best recovery approach for individuals with PFP.

Willy is an assistant professor in UM's School of Physical Therapy and Rehabilitation Sciences.

"While it might be tempting to seek quick fixes for knee pain, there is no evidence that non-active treatments alone, such as electrical stimulation, lumbar manipulations, ultrasound or dry needling, help persons with PFP," he said. "Persons with PFP should seek clinicians who use exercise therapy for the treatment of this injury."

The recommendations were published Sept. 1 as a Clinical Practice Guideline in the Journal of Orthopaedic & Sports Physical Therapy, the official scientific journal of the Academy of Orthopaedic Physical Therapy. The Clinical Practice Guideline aims to improve the quality and standardization of care provided to patients with knee pain while also providing reimbursement guidelines for insurance companies.
Key takeaways from the Clinical Practice Guideline include:

An exercise program that gradually increases activities such as running, exercise classes, sports or walking, is the best way to prevent PFP.

Adolescent athletes who specialize in a single sport are at 28% greater risk of PFP than athletes who participate in a variety of sports.

An important way to reduce the risk of PFP in military populations is maximizing leg strength, particularly the thigh muscles.

Pain does not always mean there is damage to the knee.

Although the number of women being diagnosed and dying of ovarian cancer is declining, recurrence, drug resistance and mortality remain high for women with high-grade serous ovarian carcinoma, the most common form of epithelial ovarian cancer. A new study in the journal eLife by University of California San Diego School of Medicine researchers links changes in the gene for the protein focal adhesion kinase, or FAK, to the cancer's ability to survive chemotherapy.

"We have linked elevated levels of FAK, or gene amplification, to the survival of cancer stem cells in a new tumor model," said David D. Schlaepfer, PhD, professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego School of Medicine, UC San Diego Moores Cancer Center researcher and co-principal investigator. "This was not expected. We knew FAK helped tumors to spread, but we were surprised to find that FAK supports DNA repair in the most important stem-like cells of the tumor. This may be an important tool that tumors use to resist platinum chemotherapy, which is the current standard of care."

In the majority of patients, ovarian tumors exhibit high levels of FAK, said Dwayne G. Stupack, PhD, associate professor in the Division of Gynecologic Oncology at Moores Cancer Center and co-principal investigator.

"There are drugs being tested in early phase clinical trials, including at UC San Diego Health, that inhibit FAK," said Stupack. "When we treated mice that had chemo-resistant tumors with a FAK inhibitor they responded to chemotherapy. Mice that did not receive the FAK inhibitor were resistant. By understanding the biology behind this, it can help us prepare better combinations of drugs for the clinic."

The ROCKIF Trial: Re-sensitization of Carboplatin-resistant Ovarian Cancer With Kinase Inhibition of FAK, led by Michael McHale, MD, professor in the UC San Diego School of Medicine Department of Obstetrics, Gynecology and Reproductive Sciences and chief of the Division of Gynecologic Oncology Services at UC San Diego Health, is investigating the combination of the investigational FAK inhibitor defactinib with the chemotherapy drugs carboplatin and paclitaxel for patients with chemo-resistant ovarian cancer.

"If we can prevent recurrence, we may be able to provide great benefit to patients," said McHale, a co-author on the study.

The National Cancer Institute (NCI) estimates that 22,350 women will be diagnosed with ovarian cancer in 2019 and 13,980 will die. Approximately 1 in 70 women will be diagnosed with this disease in their lifetime. Breast cancer affects nine times more women than ovarian cancer, but according to the NCI, almost nine out of 10 women will survive five years or longer with breast cancer. More than half of women with ovarian cancer will die within five years of diagnosis.

Cure or remission is dependent on the elimination of all cancer cells, including microscopic disease. Ovarian cancer cells often spread to other parts of a woman's body before an official diagnosis. The cells can grow as tiny clumps or as larger balls, called tumorspheres. In the majority of patients, ovarian cancer cells develop chemotherapy resistance.

The collaborative study, led by Schlaepfer and Stupack, focused on high-grade serous ovarian carcinoma, a subtype of epithelial cancer that starts in the outer surface of the ovaries or fallopian tubes. It makes up approximately 52 percent of malignant ovarian cancer and accounts for the highest number of deaths.

Researchers compared ovarian cancer cells in mouse models at early and late stages of the disease. The late-stage, aggressive cells exhibited greater genetic changes, and could grow as tumorspheres in lab dishes. One of these changes affected the gene for FAK, which was found to have more copies than normal.

The FAK protein is an enzyme that helps cancer cells move around. In cells from mice with late-stage cancer, FAK was over-active and present at high levels. When grown as tumorspheres, the FAK-overactive tumors were more resistant to chemotherapy than their early-stage counterparts. Among patients who had received chemotherapy, the team found that surviving tumor cells also displayed high levels of FAK activity.

To understand how FAK makes ovarian cancer cells resistant to chemotherapy, the researchers used gene-editing to delete the FAK gene. They found that, without FAK, cells became deficient in a group of detoxifying enzymes as well as others that repair damaged DNA.

"Patients with ovarian cancer generally respond well to first-line therapy, but in most cases, the cancer returns," said Schlaepfer.

"We know that a subpopulation of stem-like cancer cells can survive chemotherapy and lead to recurrence, drug resistance and even death," said Schlaepfer. "These findings suggest FAK is an important and potential therapeutic vulnerability underlying tumor recurrence."

Emory University cardiologist Laurence Sperling, MD, introduced the World Heart Federation's (WHF) new roadmap aimed at reducing the global burden of cardiovascular disease (CVD) in people living with diabetes at the joint European Society of Cardiology (ESC) Congress 2019 and World Congress of Cardiology in Paris on Monday, Sept. 2.

The Roadmap is a key reference document for anyone involved in the planning, organization, implementation, monitoring and evaluation of approaches related to CVD prevention in people living with diabetes. It outlines a vision of an ideal pathway of care, potential roadblocks along this pathway and proposed solutions, with examples from practice.

Rapid urbanization, unhealthy diets and increasingly sedentary lifestyles have resulted in fast-growing rates of obesity and diabetes, with an estimated 425 million people currently living with type 2 diabetes worldwide. Alarmingly, the situation is set to deteriorate further in the coming decades, with the total number of people with diabetes predicted to increase to over 600 million by 2045. It has been estimated that globally, up to 50 percent of people with diabetes are unaware of their disease.

While diabetes is treatable, even when glucose levels are under control it greatly increases the risk of CVD - people with diabetes are two to three times more likely to have increased risk of coronary artery disease, stroke, myocardial infarction and angina pectoris compared to those without diabetes. Prevention of CVD in people with diabetes is a necessity, and preventive strategies predominantly focus on lifestyle management and risk factor interventions.

Developed in partnership with the International Diabetes Federation (IDF), the Roadmap draws on the expertise of diabetes expert clinicians, researchers, implementation science experts and patients from around the world, and presents an integrated approach to patient care, involving the patient perspective, healthcare system perspective and health policy perspective.

Sperling, who is chair of the CVD and Diabetes Roadmap Writing Group and director of the Emory Heart Disease Prevention Center explains, "We have identified important gaps in the care of people living with diabetes who are at high cardiovascular risk, and focused on priorities and key action areas to close these gaps. We also provide an implementation toolkit for successful translation of the Roadmap to national and local initiatives, aiming to ensure that as many people living with diabetes as possible receive optimal preventive care and treatment."

In 2014, the WHF launched an initiative to develop a series of Global Roadmaps, with the aim to identify potential roadblocks on the pathway to effective prevention, detection and management of CVD, along with evidence-based solutions to overcome them. The WHF Global Roadmap on the prevention of CVD among people living with diabetes will be published as open-access in the WHF journal, Global Heart and can also be found at http://www.cvdroadmaps.org.

"Diabetes and its related CVD complications are a huge global issue, says Professor Karen Sliwa, president of the WHF. "All over the world, due to limited resources, countries are struggling to provide the necessary preventive or medical care, with a disproportionate burden falling on low-and middle-income countries. Given the worldwide impact of the epidemic of CVD and diabetes, we decided to take action to address it globally through this new roadmap on the prevention of CVD among people living with diabetes."

The Roadmap publications have become the cornerstone of WHF activities as resources for implementation to guide initiatives to support heart health globally, translating science into policy and influencing agencies, governments and policymakers alike. With this framework, countries can develop or update national non-communicable disease (NCD) programs. The overall aim is to drive efforts within national agendas to meet the ambitious target set out in the UN Sustainable Development Goals: a 30 percent reduction in premature mortality caused by NCDs, including CVD, by 2030.

"In order to be implemented successfully, the CVD and diabetes roadmap requires committed global action," says Sperling. "Launching the Roadmap at the largest cardiovascular congress in the world is the perfect forum to raise awareness of this impactful global epidemic. Our goal is to demonstrate how utilization of this roadmap can help a broad base of stakeholders begin to tackle the problem and make a longstanding difference."

Water fetching is associated with poor health outcomes for women and children, including a higher risk of death - according to new research from the University of East Anglia.

A study published today reveals that adults collecting water is associated with increased risk of childhood death, and children collecting water is associated with increased risk of diarrheal disease.

Any household member collecting water is associated with reduced likelihood that a woman will give birth in a health care facility. Women or girls collecting water is associated with reduced uptake of antenatal care and increased odds of leaving young children under five alone for an hour or more.

The research, which involved more than 2.7 million people in 41 countries, is the first to analyse the relationships between water carriage, access to clean drinking water, sanitation and maternal and child health using the UNICEF multiple indicator cluster survey data.

Senior author Prof Paul Hunter, from UEA's Norwich Medical School, said: "Hundreds of millions of people carry water each day, and it is usually the task of women and girls from the poorest families. But until now, little has been known about the health outcomes associated with fetching water.

"We wanted to find out more about the health implications of fetching water, as well as the outcomes of using unsafe water supplies, inadequate access to improved sanitation - particularly in relation to the health of women and children."

Prof Hunter and Dr Jo Geere, from UEA's School of Health Sciences, studied data from more than 2.7 million people in 41 low to middle-income countries, looking for associations between access to drinking water, sanitation and health.

They studied health outcomes including the risk of child deaths, diarrhoea in children under five, low child weight and height, the number of women giving birth in a health care facility, the uptake of antenatal care and whether young children were being left alone for long periods.

Prof Hunter said: "We found that having to carry water home and low levels of sanitation are associated with a range of adverse maternal and child health outcomes.

"Adults fetching water is associated with an increased risk of child death, and children collecting water is associated with increased odds of childhood diarrhoea.

Dr Geere said: "Water fetching by any household member is associated with reduced odds of a woman giving birth in a health care facility.

"And women or girls collecting water is associated with reduced uptake of antenatal care and increased odds of regularly leaving a child under five alone at home for over an hour.

Dr Geere said: "Mothers face a Hobson's choice when they go out to fetch water. They must either leave their child or children at home alone, or take them along what is often an unsafe route.

"Therefore, a child or children may be left unsupervised for the time it takes to walk to a water source, queue up, collect the water and return.

"Unsupervised children are likely to be at more risk of death from accidental injury or simply from reduced parental care when it is needed - for example during illness or when they are very young.

"Alternatively, if mothers take their young child with them to collect water, the route may be unsafe due to extreme environmental conditions, hazardous traffic, or interpersonal violence.

"Our findings indicate that the amount of time and energy taken for water carriage also means that women don't have time to attend antenatal clinics and many don't give birth in a health care facility.

"Fetching water may also exacerbate under-nutrition which may in turn impact pregnancies and breastfeeding - increasing the risk of child mortality. And many of the studies we looked at reported fatigue and tiredness affecting water carriers."

The research shows that improving access to water and sanitation is associated with better health outcomes for women and children.

"Our findings are consistent with another study from Ethiopia, which showed that when taps were installed closer to home, the monthly risk of child death was 50 per cent lower among children of the women with access to the new taps," said Prof Hunter. "This really shows the difference that improved access to clean water makes.

"Living in a household without a flush toilet was associated with a 9-12 per cent higher risk of child death than living in a household where members usually used flush toilets.

"But having access to water in homes and having good sanitation is associated with big improvements to the health of women and children.

"Children born into communities with improved sanitation were 12 per cent less likely to die than those born into communities with poor sanitation," he added.

No drug can cure a paradox. That basic truth is at the heart of a new Stanford-led study highlighting how poverty traps make it impossible to eradicate a potentially deadly disease with current approaches.

The study, published in the American Journal of Tropical Medicine and Hygiene, looks at why years of mass drug administration in Senegal have failed to dramatically alter infection rates of schistosomiasis, a parasitic disease that lurks in waterborne snails and affects more than 200 million people worldwide. It finds that neither drugs nor people's relatively sophisticated understanding of disease risks can overcome the inevitable exposure caused by imperatives of subsistence living. The researchers call for greater focus on the role of socio-economic and environmental systems, and engaging communities in the design of disease control programs.

"The field of tropical medicine has focused primarily on mass drug administration programs," said lead author Andrea Lund, a PhD student in the Emmett Interdisciplinary Program in Environment and Resources within Stanford's School of Earth, Energy & Environmental Sciences. "These have worked in many places, but there are persistent hot spots where you need to come at the problem from social and environmental angles too."

Although charity evaluation services consistently rank mass drug administration programs among the most effective developing world public health interventions, the efforts often fail to eradicate disease in the long run. That's because they don't address the root causes that lead to reinfection time after time, according to Lund.

Obstacles to a cure

Schistosomiasis is a disease caused by a parasitic worm and transmitted to humans by freshwater snails that serve as the parasite's intermediate host. The disease is widespread across tropical latitudes, with the vast majority of cases in sub-Saharan Africa. The snails release infective larvae into freshwater, where they burrow into people's skin. Symptoms range from abdominal pain and diarrhea to infertility, permanent organ damage and bladder cancer. Chronic schistosomiasis can affect cognitive development and labor productivity, according to some studies.

Nearly 40 years after being introduced, praziquantel - a drug used to clear schistosome parasites from people - has yet to make a dent in the global burden of the disease. That's because treated people often re-enter contaminated water, repeatedly exposing themselves to reinfection.

Lund is part of a team that has been trying to understand the obstacles to a cure and ways around them. Led by Stanford disease ecologist Susanne Sokolow and biologist Giulio De Leo (both co-authors on the study), the group has shown that ecological tactics aimed at controlling schistosomiasis are the most effective way to reduce the disease's prevalence. The team received early funding from the Stanford Woods Institute for the Environment for a project to reintroduce native snail-eating prawns to local water sources, and has since established the Program for Disease Ecology, Health and Environment at Stanford with a grant from the Stanford Institute for Innovation in Developing Economies. The program, supported by Woods and the Stanford Center for Innovation in Global Health, focuses on finding sustainable ecological solutions to a range of diseases.

Sophisticated understanding

For the study, Lund and her colleagues surveyed residents of villages along the Senegal River, a region with persistently high rates of schistosomiasis despite yearly school-based mass administration of praziquantel since 1999. People explained how life in their rural, resource-poor area is inextricably intertwined with the river. Common livelihoods, such as agriculture and fishing, depend on contact with the waterway. So do chores, such as washing clothes, and hygiene practices, such as bathing and children's play.

A 53-year-old man from one riverside village who spoke with one of the researchers summed up the catch-22: "That water, we cannot touch it. We cannot abandon it. If we abandon it, we will all become unemployed."

"There is a feeling of inevitability around schistosomiasis infection, given the constraints of poverty," said Sokolow, a senior research scientist at Woods. "That jibes with the experience of the many years of efforts to distribute pills and carry out educational campaigns in the region without a huge drop in schisto transmission or infection. It's the quintessential wicked problem."

Residents expressed a relatively sophisticated knowledge about the environmental nature of schistosomiasis, including the fact that infection risks increase at midday - an observation borne out by the tendency of snails to release free-swimming parasite larvae into the water at the same time of day. With this knowledge, some residents had developed personal strategies or village-wide policies - enforceable by fines - to minimize exposure by avoiding the river at certain times.

Good leadership and community engagement were among the strongest indicators of success in overcoming these obstacles. This capacity to organize suggests that communities could take the lead in implementing environmental and social interventions - ranging from prawn re-introduction to the construction and maintenance of water and sanitation facilities or behavior change programs. This would ensure interventions are locally acceptable and can be sustained over time. This type of engagement with communities could reduce the amount of parasite transmission in the environment and improve outcomes of mass drug administration in areas where they have had limited success, according to the researchers.

"Ultimately, I see these findings making a case for further investment in environmental solutions - such as prawn re-introduction," Lund said. "This may be the only way to reduce the risk of schistosomiasis in settings where the disease burden remains high even in the presence of treatment programs."

ADELAIDE, AUSTRALIA: A major new study led by Flinders University Professor Derek Chew shows that up to 70% of patients presenting to Australian hospital emergency departments with chest pain could be safely discharged in less time than they currently are under standard Australian protocols.

The system has the potential to significantly reduce wait times and rates of hospital admissions while maintaining health outcomes for patients - not just in Australia but internationally.

The world-first 'RAPID-TnT' trial focuses on a more sensitive cardiac blood test for a protein called Troponin T, paired with a faster testing protocol.

Current protocols see patients with suspected acute coronary syndrome (ACS) tested upon presentation and then re-tested three hours later to compare protein levels.

Under the trial, patients presenting to hospital were randomly allocated to a 0-1 hour testing group or 0-3 hour testing group. Patients in the one-hour follow-up group on average spent one hour less in the emergency room and were significantly less likely to be admitted to hospital (33.2% compared to 45.5%)

"Currently there are around 30,000 emergency department presentations for chest pain each year in South Australia, so that represents a large number of people not unnecessarily taking up a hospital bed," says Matthew Flinders Fellow Professor Chew, also Network Director of Cardiology at Flinders Medical Centre, and leader of the Heart and Vascular Health Research program at SAHMRI.

"We continued to monitor both groups of patients and, over the next 30 days, there was no difference in the ongoing health between the two groups.

"We've shown the one-hour follow-up protocol is safe for patients. The benefits for the system as a whole are reducing crowding in EDs and reducing unnecessary hospital admissions," he says, adding wait times and admissions could be reduced even further by developing an artificial intelligence program to support doctors' decisions.

"Understandably, doctors err on the side of caution when it comes to the health of their patients. They would get a great deal of confidence from an electronic system which can accurately estimate the risk of heart attack with help from a vast database of blood test results which are measured against future health outcomes," says Professor Chew.

South Australia's Health and Wellbeing Minister Stephen Wade says this "exciting research could be a game-changer" for patients with suspected heart attacks, with potential to "dramatically cut wait time in our Emergency Departments".

"It shows our health services are services which learn and encourage learning. Yet again South Australia is leading the world in best practice in medicine," Mr Wade says. "It demonstrates how our home-grown research can drive better outcomes for patients."

Investigations for suspected acute coronary syndrome (ACS) accounts for about 10% of the 7 million presentations at Australian emergency departments (EDs) every year. However, a significant number of these patients present with "undifferentiated" symptoms such as chest pain or shortness of breath that may or may not reflect ACS.

RAPID-TnT (Rapid Assessment of Possible ACS In the emergency Department with high sensitivity Troponin T), a randomised trial involved more than 3000 patients at four large metropolitan hospitals in Adelaide, was developed in consultation with South Australian and national public hospital and other universities.

Professor Chew says: "Given the demands on our EDs, it is essential that we establish effective, evidence-based ways to quickly distinguish those who are having a heart attack from those who aren't and who can safely go home."

"While it is critical that patients with chest pain and shortness of breath present at emergency departments, we know upon investigation that a large proportion of these patients are not having a heart attack," Professor Chew says.

In a paper to be published in the forthcoming issue in NANO, a group of researchers from Guiyang, China, have conducted a study based on previous experimental research on DOX as a model drug and introduced a reverse method in which organic groups are grafted after removing the template agent. This has potential applications in the drug delivery field for better control drug release.

Mesoporous silica has potential research applications in the field of medicine. The particle size of mesoporous silica can reach the nanoscale, which allows it to withstand thermal and mechanical stresses as well as pH and oxidation degradation with low toxicity and good biocompatibility. Taking advantage of these characteristics, the group of researchers from Guizhou University and Guiyang Vocational and Technical College have improved the drug-loading capacity by adjusting the pore diameter through surface modification to achieve controlled and targeted release of drugs.

Although these organic functional groups can ensure the good adsorption of drugs, such as common model drugs aspirin and DOX, their loading capacity is low and loading takes a long time. To overcome these shortcomings, the number of functional groups were increased to increase the number of activity sites. Based on previous experimental research on DOX as a model drug, following Stober's theory of the synthesis of mesoporous silica in a water-methanol-ammonium hydroxide-TEOS system at different temperatures, mesoporous silica spheres with diameters ranging from 80 to 290 nm were obtained. These showed improved effects of different physical and chemical characteristics on drug loading due to the functionalization of organic groups. 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane(NQ-62) and succinic anhydride (SA) were utilized as modifying agents in organic functionalization processing, which improved the drug loading, possessing great potential to control drug release.

Paris, France - 3 Sept 2019: Statins are linked with reduced mortality in patients with peripheral arterial disease, even when started late after diagnosis, reports a study presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1) Patients who stop the drug are at similar risk to those who never start. The research shows the importance of starting and adhering to lifelong medication, preferably at a high dose.

Around 200 million people worldwide have peripheral arterial disease (PAD), a condition in which arteries in the legs are clogged. This restricts blood flow to the legs and raises the chances of stroke and heart attack. Around 30% of patients have pain and cramping in their legs when they walk - referred to as intermittent claudication - while others have gangrene in the feet due to poor circulation.

Statins are recommended for all patients with PAD, together with smoking cessation, exercise, healthy diet, and weight loss.(2) Statins diminish the risk of stroke and heart attack by reducing low-density lipoprotein (LDL) cholesterol, which causes blocked arteries (atherosclerosis).

But adherence to statins is low: over the past five years, just 57% of patients in Europe took the medication as directed. In 2016 to 2017, only one-third of patients on statins reached the LDL cholesterol target of below 1.8 mmol/L (70 mg/ dl).(3)

This study examined whether adherence to statin therapy influenced survival in patients with symptomatic PAD. The study enrolled 691 patients admitted to hospital between 2010 and 2017 and followed-up for a median of 50 months.

At the beginning of the study, 73% of patients were on statins, increasing to 81% at the 50-month follow-up. The dose of drug also increased between the two time periods, which was paralleled by a significant drop in LDL cholesterol from 97 to 82 mg/dL.

Patients who stopped taking a statin had a similar mortality rate (33%) to those who never took the drug (34%). Adhering to statins throughout the 50 months was linked with a 20% rate of death.

Taking high-dose statins throughout the study was linked with the lowest mortality rate (10%), while reducing the dosage during the study was related to the highest death rate (43%).

Study author Dr Jörn Dopheide of Bern University Hospital, Switzerland said: "The study shows that adherence to statins is essential for the best prognosis. We also show that it is never too late to start medication and benefit from it. On top of that, it is crucial not to reduce the dose because LDL cholesterol levels rise again, thus increasing the overall risk on top of the residual risk for further events."

He concluded: "All PAD patients should take statins, preferably very potent statins, like rosuvastatin 40 mg or atorvastatin 80 mg, or at the highest tolerable dose. In the rare case of statin intolerance, which was around 2% in our study, alternative lipid lowering therapies must be considered."

Paris, France - 3 Sept 2019: A study in nearly 1.7 million 18-year-old boys has found that higher body mass index (BMI) is linked with greater risk of a heart attack before 65 years of age. The research is presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1 )

Study author Dr Maria Aberg of the University of Gothenburg, Sweden said: "We show that BMI in the young is a remarkably strong risk marker that persists during life. Our study supports close monitoring of BMI during puberty and preventing obesity with healthy eating and physical activity. Schools and parents can play their part by encouraging teenagers to spend less leisure time in front of a screen and providing healthy food."

The study included all Swedish men born between 1950 and 1987 and enlisted for mandatory military service at the age of 18. When enlisting, all 1,668,921 men underwent extensive physical and psychological examinations, such as BMI, blood pressure, IQ, and tests of cardiovascular and muscular fitness. Men were followed up between 1969 and 2016 for a maximum follow-up of 46 years. Swedish patient and death registries were used to record how many had a fatal or nonfatal heart attack later in life.

There were 22,412 heart attacks which occurred at an average age of 50 (maximum age 64). Rising BMI in 18-year-olds was associated with an elevated risk of a heart attack before age 65, even after adjustment for age, year of conscription, comorbidities at baseline, parental education, blood pressure, IQ, muscle strength, and fitness.

The increase in risk started at BMI 20 kg/m2, a level considered normal, then rose gradually, culminating in a nearly 3.5-fold elevated likelihood of heart attack in the severely obese (BMI 35 or higher). Compared to adolescents with BMI of 18.5 to 20.0 kg/m2, hazard ratios for the risk of heart attack were 2.64 and 3.05 for BMIs of 27.5 to 29.9 and 30 to 34.9, respectively.

Commenting on why risk started even at healthy BMIs, Dr Aberg said: "This is an exploratory, population-based study meaning we report associations, but can only speculate on mechanisms. It is possible that altered lipid metabolism, inflammation, and oxidative stress contribute to atherosclerosis at BMIs over 20. In addition, reference values for normal BMI in late adolescence may need to be reconsidered."

She noted that since the study only included men, the results cannot be extrapolated to women.

Dr Aberg concluded: "Our finding of a link between adolescent BMI and heart attack in adulthood supports our previous results for heart failure. As the prevalence of overweight and obesity in young adults continues to escalate, we may start to see correspondingly higher rates of heart attacks and strokes in the future. Urgent action is needed by parents, schools, and policy makers to halt the obesity epidemic in children and young people."

HAMILTON, ON (Sept. 3, 2019) - Cardiovascular disease (CVD) is the major cause of death among middle-aged adults around the world; however, in high-income countries deaths from cancer have become twice as frequent as those from CVD.

The findings come from the first large prospective international study documenting the frequency of common diseases and death rates in high-, middle- and low-income countries using a standardized approach.

The research, published in The Lancet today and presented at the European Society of Cardiology Congress, is from the Prospective Urban Rural Epidemiology (PURE) study led by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences in Hamilton, Canada.

For this paper, the research involved more than 162,500 adults aged 35 to 70 from 21 countries who were followed for a median of 9.5 years.

"The fact that cancer deaths are now twice as frequent as CVD deaths in high-income countries indicates a transition in the predominant causes of death in middle age," said Salim Yusuf, principal investigator of the study, executive director of PHRI and a professor of medicine at McMaster.

"As CVD declines in many countries because of prevention and treatment, cancer mortality will likely become the leading cause of death globally in the future.

"The high mortality in poorer countries is not due to a higher burden of risk factors, but likely other factors including lower quality and less health care."

The high-income countries (HIC) in the study were Canada, Saudi Arabia, Sweden and United Arab Emirates. The middle-income countries (MIC) were Argentina, Brazil, Chile, China, Columbia, Iran, Malaysia, Palestine, Philippines, Poland, Turkey and South Africa. The lower-income countries (LIC) were Bangladesh, India, Pakistan, Tanzania and Zimbabwe.

Yusuf added that the results are likely to be applicable to other countries with similar economic and social characteristics and health care.

In a pattern observed for all causes of death except cancer, overall mortality per 1,000 person years was lowest in HIC (3.4%), intermediate in MIC (6.9%) and highest in LIC (13.3%).

Regarding deaths, CVD was the commonest cause overall at 40 per cent, but that ranged from only 23 per cent in HIC to 41 per cent in MIC and 43 per cent in LIC, even though the CVD risk factors were highest in the HIC and lowest in LIC. Cancer was the second most frequent cause of death at 26 per cent of deaths, but this proportion varied and was responsible for 55 per cent of deaths in HIC, 30 per cent in MIC and 15 per cent in LIC.

The other major findings of the study were:

With higher country income, a higher proportion of deaths and hospitalizations were from non-communicable diseases compared to infectious diseases;

The higher rates of CVD and related deaths in poorer countries compared to richer countries occurred despite much lower CVD risk factors in poor countries;

There is an inverse association between use of hospital care and effective medication versus deaths, suggesting that lower quality health care may be responsible, at least in part, for the higher mortality in poorer countries.

"The implications are that in HIC, while continued efforts to prevent and treat CVD should continue, new efforts to reduce cancer are required," said Darryl Leong, the co-lead author of the study, scientist at PHRI, and assistant professor of medicine at McMaster University.

Gilles Dagenais, professor emeritus of medicine at Laval University and lead author of one of the PURE papers, added: "If ways of lowering CVD deaths that have been effective in high-income countries are implemented in middle- and lower-income countries, we could expect large drops in CVD deaths there as well over time. If that happens, we might also expect that cancer will become relatively more common as a cause of death."

Paris, France - 3 Sept 2019: After a heart attack, patients with diabetes are at greater risk of heart failure and subsequent death than those without diabetes, according to late breaking results from the FAST-MI registry presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

Principal investigator Professor Nicolas Danchin of the European Hospital Georges Pompidou, Paris, France said: "The findings emphasise the importance of preventing diabetes with better lifestyles, including avoiding obesity and overweight with a healthy diet and being physically active. In patients with diabetes, and especially those with coronary artery disease or previous heart attack, we need treatments that reduce blood sugar and decrease the risk of heart failure."

Diabetes is a growing public health concern. High blood sugar levels slowly attack the artery walls and
facilitate deposits of cholesterol. The ensuing lipid-rich plaques can block arteries in the heart, brain, and legs, raising the risks of heart attack, stroke, and claudication with possible amputation.

In theory, high blood glucose levels may impair the capacity of heart cells to contract and propel blood throughout the body, leading to heart failure. However, whether patients with diabetes are at greater risk of developing heart failure when suffering a heart attack has not been extensively studied.

The study used data from nationwide surveys carried out in France between 2005 and 2015 in 12,660 patients hospitalised for a heart attack. The researchers analysed whether diabetic patients were more likely than non-diabetic patients to develop heart failure during their hospital stay and in the year after. In patients with diabetes, they compared five-year mortality in those readmitted for nonfatal heart failure during the year following their heart attack versus those who did not develop heart failure.

Nearly 25% of patients hospitalised for an acute myocardial infarction during the ten-year period had known diabetes (3,114 of 12,660 patients). "This figure is consistent with what most cardiologists have found among their heart attack patients and illustrates how common diabetes is," said Prof Danchin.

During hospitalisation for myocardial infarction, 32% of patients with diabetes developed heart failure compared to 17% of patients without diabetes. After adjusting for other factors that could cause heart failure, those with diabetes had a 56% higher risk than those without of developing heart failure.

Likewise, in those who survived the heart attack, 5.1% of diabetic patients were hospitalised for nonfatal heart failure in the following year compared to 1.8% of non-diabetic patients. After adjustment, this equated to a 44% raised risk of heart failure in those with diabetes.

Finally, among patients with diabetes who were alive one year after their heart attack, 56% of patients who had been hospitalised for heart failure during that year died during the subsequent four years compared to 21% of those without heart failure. After adjustment, this amounted to a 73% higher risk of five-year mortality in those with heart failure. The increased risk was particularly marked for diabetic patients requiring insulin.

Prof Danchin said: "Our study shows that diabetes is associated with a considerably increased risk of developing heart failure after a heart attack. Furthermore, diabetic patients who develop heart failure in the year after a heart attack have a much higher risk of dying in the following years."

He concluded: "More efforts are needed to prevent diabetes. In addition, better management is required for diabetic patients who have a heart attack to avoid heart failure and its detrimental long-term consequences."

Osaka, Japan - Hepatoblastoma is a rare form of liver cancer affecting just a few individuals per million. However, it is the leading cause of liver cancer in infants and young children, with most patients diagnosed before their third birthday.

While advances in surgery and chemotherapy have meant that the prognosis for hepatoblastoma patients is generally quite good, aggressive forms of the disease leave some young patients with few treatment options and poor long-term survival rates. In a study published at 18:00 (JST) on Aug. 28 in Nature Communications, researchers from Osaka University have built on prior research to make a breakthrough in our understanding of the causes of hepatoblastoma, identifying a gene that could be key to developing a targeted therapy.

As far back as 1999, researchers realized that a large number of hepatoblastoma patients--up to 90% in some cases--carry mutations in a gene called β-catenin. As part of the Wnt/β-catenin signaling pathway, the β-catenin protein activates genes needed for cellular growth and differentiation. If left unchecked, β-catenin accumulation can result in tumor formation. Mutations in Wnt/β-catenin signaling components often lead to β-catenin accumulation and are common in several forms of cancer.

"We decided to screen uncharacterized Wnt/β-catenin target genes in liver tumor cells to try and identify novel genes with a role in the development of hepatoblastoma," explains lead author of the study Shinji Matsumoto. "One of the most abundantly expressed genes was growth regulation by estrogen in breast cancer 1 (GREB1), which is a well-known estrogen-responsive gene implicated in the growth of breast cancer cells."

While well-characterized in breast cancer, no one had determined that GREB1 was actually a target of Wnt/β-catenin signaling, and its role in non-hormone-sensitive tumor development was unconfirmed.

But after studying the protein in more detail, it became obvious to the researchers that GREB1 could be a major player in the development of hepatoblastoma.

"Overexpression of β-catenin in a mouse liver cancer model resulted in tumor formation and an increase in GREB1 expression," says corresponding author Akira Kikuchi. "If we then suppressed the production of GREB1, we saw a decrease in hepatoblastoma cell proliferation and therefore fewer tumors in the study animals."

Because GREB1 is active in the nucleus, the researchers attempted to prevent tumor formation using amido-bridged nucleic acid-modified antisense oligonucleotides. These small single-stranded DNA molecules specifically interfere with the production of target proteins by binding to the mRNA. Significantly, the GREB1-targeted oligonucleotides successfully decreased GREB1 production and suppressed the formation of hepatoblastoma tumors.

Using this strategy, it is hoped that a GREB1-targeted therapy can now be developed to specifically treat hepatoblastoma.

Human beings are constantly and simultaneously in contact with numerous chemical agents, meteorological conditions, and other exposures derived from our surroundings and everyday habits. Studying the effects of individual exposures is very challenging and can lead to misleading results, since exposures generally do not occur in isolation. Therefore, a new exposome-based approach--analysing all of an individual's environmental exposures, starting in the prenatal period, rather than studying each exposure separately--has recently gained traction in the field of environmental epidemiology.

A new study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa", used this holistic approach to analyse more than 200 environmental exposures during pregnancy and childhood. The study, published in the Journal of the American College of Cardiology, concludes that some of the exposures analysed could have an impact on blood pressure in children.

The study was carried out as part of the HELIX project, which compiles data from cohorts in six European countries (Spain, France, Greece, Lithuania, Norway and the United Kingdom), and included a total of 1,277 children and their mothers. Exposures were assessed during pregnancy and when the children were between 6 and 11 years of age. The children underwent a clinical examination that included blood and urine sample collection and blood pressure measurements.

The researchers assessed a total of 89 prenatal and 128 postnatal exposures grouped in three categories: outdoor exposures (air pollution, meteorological conditions, green spaces, etc.), chemicals (pesticides, metals, plasticisers, etc.) and lifestyle factors (diet, physical activity, sleep patterns, etc.).

"Our results show that, starting in the foetal stage, where we live, the food we eat, the air we breathe and the chemical compounds that reach our bodies can affect blood pressure before adolescence. This is important because evidence shows that children with high blood pressure are more likely to be hypertensive as adults," commented ISGlobal researcher Charline Warembourg, the lead author of the study.

Exposures associated with higher blood pressure

Statistical analysis revealed an association between various exposures and higher blood pressure in children. The exposures associated with increases in blood pressure included exposure to tobacco smoke and bisphenol-A (a plasticiser) during pregnancy and low and high fish intake during pregnancy (less than twice a week and more than four times a week, respectively).

Similarly, children with higher serum concentrations of copper and perfluorooctanoic acid (PFOA, a compound used in non-stick pots and pans, clothing, etc.) had higher blood pressure.

"Some of the associations found in children in this study, such as tobacco smoke and bisphenol-A, had already been observed in adults in previous studies," explained Warembourg. "Other associations, such as fish intake during pregnancy, are more difficult to interpret. Fish contains essential fatty acids that are necessary and beneficial, but we also know that it is a source of chemical compounds, which perhaps helps to explain why moderate fish intake is associated with better blood-pressure results."

Exposures associated with lower blood pressure

The study also identified exposures associated with lower blood pressure, such as higher outdoor temperatures during childhood and facility density in the neighbourhood where the mother lived during pregnancy. "Urban-design factors such as the number of shops, restaurants, parks and public-transport hubs determine how people use the city and get around, and they are important for health because they promote physical activity and social contact," explained ISGlobal researcher Xavier Basagaña, the last author of the study.

Where a mother lives and the temperature outside while she is pregnant, among other environmental factors, can impact whether her child is prehypertensive or hypertensive during childhood, according to a study published today in the Journal of the American College of Cardiology.

Exposure to negative lifestyle factors in pregnancy, such as obesity, physical inactivity, poor diet, and alcohol and tobacco consumption have long been established as heart disease risk factors for mothers. Only in recent years have studies begun to link these risk factors to prehypertensive status in children and their likelihood of developing hypertension, or high blood pressure, later in life.

The study included data from a total of 1,277 mother-child pairs from the Human Early-Life Exposome (HELIX) project, which pooled data of six European birth cohorts from the United Kingdom, France, Spain, Lithuania, Norway and Greece. The selected children were between the ages of 6 to 11, had stored blood and urine samples available and had no prior health problems. At the time of the examination, 10 percent of the children could be classified as prehypertensive or hypertensive.

Researchers evaluated a total of 89 prenatal maternal exposures and 128 postnatal child exposures. Of these, four broader environmental factors were determined to influence blood pressure status in children: Built environment (where the mother was living during pregnancy), outdoor temperature, fish intake and exposure to chemicals.

"This study is the first to simultaneously consider the possible effects of exposure to hundreds of environmental factors during early life on blood pressure in children," said Charline Warembourg, PhD, the study's main author from the Barcelona Institute for Global Health (ISGlobal). "Exposures were assessed through a mix of predictive modeling from home address and questionnaire and through determination of biological samples from the mother and child."

Mothers who lived in a walkable environment with access to green spaces, shops, restaurants and public transportation during pregnancy were associated with normal blood pressure in their children. Alternatively, the mothers who did not live in an urban or highly walkable environment had higher blood pressure. The researchers hypothesized that the lower blood pressure that resulted from living in an urban setting was due to the higher amount of physical activity during pregnancy.

Exposure to a higher outdoor temperature during the time of the blood pressure assessment was associated with lower diastolic blood pressure in children. Outdoor temperature has been proven in previous studies to be a known environmental factor to affect blood pressure in both adults and children.

Both low and high fish intake during pregnancy were associated with an increase in blood pressure in children. While the omega-3 fatty acids found in fish are beneficial for overall cardiovascular health, fish contaminated by chemicals or metals could reduce any positive effects of omega-3 fatty acids.

Exposure to bisphenol-A (BPA) concentrations - a chemical found in various consumer plastics - during pregnancy resulted in higher blood pressure in children, as did exposure to perfluorooctanoate (PFOA) concentrations - a chemical found in cosmetics, household cleaners or clothing. Children who had been exposed to copper during childhood also had a higher blood pressure.

"In this study, the researchers presented a comprehensive analysis of the association of early-life environmental exposures with blood pressure in children," said Andrea A. Baccarelli, MD, PhD, chair and Leon Hess professor of environmental health sciences at the Columbia University Mailman School of Public Health, in an accompanying editorial comment. "Due to the innovation shown by the researchers, this study provides a model that may greatly advance investigations of the influences of environmental exposures on human health."

This study has several limitations, including exposure misclassification and the small sample size given the large number of exposures investigated. While the present study remains at risk of false positives or negatives, it highlights that environmental exposures early in life have potentially important effects on blood pressure in children.

In 2003, a German neuropathologist proposed that Parkinson's disease, which attacks the brain, actually might originate from the gut of the patients. Researchers from Aarhus have now delivered decisive supportive evidence after seeing the disease migrate from the gut to the brain and heart of laboratory rats. The scientific journal Acta Neuropathologica has just published the results, which have grabbed the attention of neuroscientific researchers and doctors internationally.

Harmful proteins on the move

Parkinson's disease is characterised by slowly destroying the brain due to the accumulation of the protein alpha-synuclein and the subsequent damage to nerve cells. The disease leads to shaking, muscle stiffness, and characteristic slow movements of sufferers. In the new research project, the researchers used genetically modified laboratory rats which overexpress large amounts of the alpha-synuclein protein. These rats have an increased propensity to accumulate harmful varieties of alpha-synuclein protein and to develop symptoms similar to those seen in Parkinson's patients. The researchers initiated the process by injecting alpha-synuclein into the small intestines of the rats. According to professor Per Borghammer and postdoc Nathalie Van Den Berge, the experiment was intended to demonstrate that the protein would subsequently spread in a predictable fashion to the brain.

"After two months, we saw that the alpha-synuclein had travelled to the brain via the peripheral nerves with involvement of precisely those structures known to be affected in connection with Parkinson's disease in humans. After four months, the magnitude of the pathology was even greater. It was actually pretty striking to see how quickly it happened," says Per Borghammer, who is professor at the Department of Clinical Medicine at Aarhus University.

Symptoms in the intestine twenty years before the diagnosis

Per Borghammer explains that patients with Parkinson's disease often already have significant damage to their nervous system at the time of diagnosis, but that it is actually possible to detect pathological alpha-synuclein in the gut up to twenty years before diagnosis.

"With this new study, we've uncovered exactly how the disease is likely to spread from the intestines of people. We probably cannot develop effective medical treatments that halts the disease without knowing where it starts and how it spreads - so this is an important step in our research," says Per Borghammer, adding:

"Parkinson's is a complex disease that we're still trying to understand. However, with this study and a similar study in the USA that has recently arrived at the same result using mice, the suspicion that the disease begins in the gut of some patients has gained considerable support."

The research project at Aarhus University also showed that the harmful alpha-synuclein not only travel from the intestines to the brain, but also to the heart.

"For many years, we have known that Parkinson patients have extensive damage to the nervous system of the heart, and that the damage occurs early on. We've just never been able to understand why. The present study shows that the heart is damaged very fast, even though the pathology started in the intestine, and we can continue to build on this knowledge in our coming research," says Per Borghammer.