Body

Philadelphia, July 18, 2019 - Aging men with low testosterone levels who take testosterone replacement therapy (TRT) are at a slightly greater risk of experiencing an ischemic stroke, transient ischemic attack (TIA), or myocardial infarction, especially during the first two years of use, reports a study appearing in The American Journal of Medicine, published by Elsevier. The findings confirm concerns voiced by many health agencies about the potential risks associated with the treatment.

The study analyzed a large database of electronic medical records of patients enrolled in primary care practices in the United Kingdom and formed a cohort of 15,401 men, aged 45 years or older, with low testosterone levels (hypogonadism). Users of TRT had a 21 percent greater risk of cardiovascular events compared with nonusers, corresponding to an additional 128 events. The increased risk appears to be transient, declining after two years of TRT use, which the investigators attribute to a phenomenon called "depletion of susceptibles."

"Our findings show that the use of TRT was associated with an increased risk of stroke, TIAs, or cardiac arrest during the first two years of use," noted Christel Renoux, MD, PhD, Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital; and Departments of Epidemiology, Biostatistics, and Occupational Health, and Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. "There is limited evidence on the long-term clinical benefits of TRT to effectively treat the modestly declining levels of endogenous testosterone levels of aging but healthy men. We strongly recommend that clinicians proceed with caution when considering prescribing TRT and first discuss both the potential benefits and risks with patients."

The study specifically aimed to study men with low testosterone levels due to aging and not due to known secondary causes. While reported rates of hypogonadism have remained stable, prescriptions for TRT have soared in the last 20 years, TRT is increasingly prescribed to relieve nonspecific symptoms of aging, such as fatigue and a modest decline in sexual functioning. An interesting finding was that current use of TRT was associated with a decreased risk of overall mortality and past use with an increased risk. While this could indicate some protective effect on mortality, it could also be due to reverse causality, with clinicians discontinuing TRT treatment in patients with deteriorating health. The analysis did have access to the patients' prior histories and was able to adjust for comorbidities.

"Further large and methodologically sound observational studies should be conducted to reaffirm these results. Until such time, the potential cardiovascular risk of TRT should be weighed against the perceived and expected benefits among aging men, a perspective that aligns with warnings issued by health agencies," advised Dr. Renoux.

This study first appeared online in April 2019 and will subsequently be published in the September 2019 issue of the American Journal of Medicine.

Researchers at The University of Texas MD Anderson Cancer Center have discovered how an aggressive form of prostate cancer called double-negative prostate cancer (DNPC) metastasizes by evading the immune system. The investigators also reported on the pre-clinical development of a new therapy, which, when given in combination with existing immunotherapies, appears to stop and even reverse metastasis in mouse models.

DNPC is difficult to treat and frequently arises in patients previously treated with therapies that inhibit androgen receptors (AR), known to spur prostate cancer cells growth. Study findings were published in the July 18 online issue of Cancer Cell.

Filippo Giancotti, M.D., Ph.D., professor of Cancer Biology, reported that an epigenetic regulator known as the polycomb repressor complex 1 (PRC1) coordinates the initiation of metastasis by increasing the regenerative capacity of metastatic cells and by suppressing the immune system and spurring tumor blood vessel growth or angiogenesis.

"The findings open up potential new approaches to treating DNPC, which has been recognized recently as a new subtype that emerges at least in part in response to treatment with next-generation AR inhibitors," said Giancotti, "We showed that PRC1 plays a role with immunosuppression at metastatic sites in DNPC, and we developed a novel in-class inhibitor of PRC1. This inhibitor exhibited efficacy as a single treatment and cooperated with double checkpoint immunotherapy to completely suppress metastasis in pre-clinical DNPC models."

Through in vivo genetic screening, the team identified a cytokine called CCL2 as the major pro-metastatic gene induced by PRC1. CCL2 binds to a tumor cell receptor called CCR4 to boost regenerative capacity and to CCR2 in immune cells, creating an immunosuppressive microenvironment and boosting tumor blood vessel growth.

"CCL2 also attracts tumor-associated macrophages (TAMS) and regulatory T cells (Tregs), which suppresses the immune system and stimulates angiogenesis," said Giancotti. "Our study showed that targeting PRC1 inhibits recruitment of TAMS and Tregs, suppressing tumor metastasis."

Giancotti's team combined PRC1 with two types of immunotherapy agents, which attracted important immune cells called CD4 and CD8 T cells, resulting in "maximal induction" of tumor cell death in mice.

"This indicates that the inhibiting TAMS and Tregs with PRC1 inhibitors enables double checkpoint therapy to not only recruit but also to activate T cells, thus causing metastasis regression," said Giancotti.

A new class of diabetes medications is masking the potentially dangerous condition of ketoacidosis at the time of surgery. Testing for acid load in the blood of diabetes sufferers who are taking gliflozin medications is needed in order to avoid complications associated with ketoacidosis - a potentially lethal build-up of acid in the blood.

A study published in the British Journal of Anaesthesia found 42 cases of people with diabetes who presented for various surgeries, while taking gliflozin medications, experienced ketoacidosis while their blood sugar level was normal.

"Euglycaemic ketoacidosis is deceiving and likely to be missed easily as it presents with near or low-normal blood sugars," says Dr Venkatesan Thiru, Senior Clinical Lecturer, the University of Adelaide.

"Gliflozin medications are being increasingly used to protect people against heart and kidneys diseases. They work in the kidneys to excrete excess sugar in diabetic patients' urine.

"The condition may happen in the lead-up to surgery when patients cannot eat and drink normally.

"It is difficult to recognize euglycaemic ketoacidosis as blood sugar levels are usually normal."

Diabetic ketoacidosis is a serious complication when the body does not have enough insulin and can't use sugar to generate energy. Instead, the body uses fat to produce energy and this process leads to accumulation of acids called ketones in the body. Blood sugar levels are always high with this ketone build-up which is called diabetic ketoacidosis. If this problem is not treated, it can lead to coma and death. It is likely to happen with severe infection, loss of hydration, illness or during surgery.

"Euglycaemic ketoacidosis can happen in people with both type 1 and type 2 diabetes. Unless special tests are done to assess the acid load in the body, clinicians can miss this complication. The symptoms are similar to other events during and after surgery such as mild acid build up, vomiting and abdominal pain," says Dr Thiru.

"Failure to identify and treat this condition can result in unnecessary tests looking for other medical and surgical problems after surgery.

"In the 42 cases identified in the study, euglycaemic ketoacidosis occurred within a few hours after surgery and up to a few weeks after their operation. Changes in patients' diabetes medications, diet and illnesses were found to be responsible.

"Patients who undertake weight reduction surgery when they are on a special diet program are at an increased risk of experiencing this complication.

"Extra vigilance is the key in reducing this complication and patients should be educated about this. Care givers should ask for acid load to be tested by checking for blood ketone levels. The good news is that some of the latest blood glucose home monitoring kits can also test for acid build up.

"While the rate of this incident occurring in diabetic patients having surgery is unknown at this stage, our team is embarking on a study to assess the ongoing risk," says Dr Thiru.

Researchers at the University of Sussex have identified how differences in the genetic sequence of the two main strains of the cancer-associated Epstein-Barr virus (EBV) can alter the way the virus behaves when it infects white blood cells.

When EBV enters white blood cells it drives them to grow rapidly and continuously, making them 'immortal'. In some cases this can lead to the development of lymphoma, a type of blood cancer.

There are two main strains of the virus worldwide and although they can both cause cancer, in the laboratory, one strain (type 1) is able to drive white blood cells to become immortal better than the other (type 2).

While scientists already knew that the different properties of the two strains were caused by a protein called EBNA2, which is produced by EBV, until now they didn't know how it could cause the viruses to act so differently.

In a new research paper published in the journal PLOS Pathogens, Professor Michelle West together with Dr Erika Mancini at the University of Sussex and Professor Paul Farrell at Imperial College London, have identified a molecular reason for the difference in activity between the two strains.

Prof West said: "EBNA2 is kept in check by contact with a protein normally found in white blood cells; BS69. This contact damps down EBNA2 function but does not block it entirely.

"While type 1 has two contact points for BS69 the sequence changes in type 2 result in the creation of a third contact point.

"This additional contact damps down type 2 EBNA2 function to a greater extent, helping to explain why this strain of EBV is less efficient at driving white blood cell growth."

The research, funded by the charity Bloodwise and the Medical Research Council helps shed light on how proteins already present in white blood cells can restrict some strains of the virus more than others.

Prof. West said: "It is assumed that because type 2 strains of EBV are less efficient in the laboratory, these strains of EBV might be less cancer promoting, but oddly there is no evidence to support this.

"We do know that type 2 strains of EBV are more common in certain parts of Asia and Africa, and we could speculate that immortalising white blood cells less efficiently may somehow be an advantage to the virus in infecting people in these parts of the world.

"New research also shows that type 2 strains of EBV are able to infect a different kind of white blood cell, the T cell, so it may be that type 2 strains use an alternative route to enter the body."

Professor West's team, in collaboration with Professor Farrell and Dr White at Imperial College, will now investigate the impact of strain variation on the biology of EBV further, thanks to recent funding for a 3-year project by the Medical Research Council.

AURORA, Colo. (July 18, 2019) - Mothers living near more intense oil and gas development activity have a 40-70% higher chance of having children with congenital heart defects (CHDs) compared to those living in areas of less intense activity, according to a new study from researchers at the Colorado School of Public Health.

"We observed more children were being born with a congenital heart defect in areas with the highest intensity of oil and gas well activity," said the study's senior author Lisa McKenzie, PhD, MPH, of the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus.

At least 17 million people in the U.S. and 6% of Colorado's population live within one mile of an active oil and gas well site.

The study was published today in the peer-reviewed journal Environment International.

The researchers studied 3,324 infants born in Colorado from 2005-2011. They looked at infants with several specific types of CHDs.

Researchers estimated the monthly intensity oil and gas well activity at mother's residence from three months prior to conception through the second month of pregnancy. This intensity measure accounted for the phase of development (drilling, well completion, or production), size of well sites, and production volumes.

They found mothers living in areas with the most intense levels of oil and gas well activity were about 40-70% more likely to have children with CHDs. This is the most common birth defect in the country and a leading cause of death among infants with birth defects. Infants with a CHD are less likely to thrive, more likely to have developmental problems and more vulnerable to brain injury.

Animal models show that CHDs can happen with a single environmental exposure during early pregnancy. Some of the most common hazardous air pollutants emitted from well sites are suspected teratogens - agents that can cause birth defects - known to cross the placenta.

The study builds on a previous one that looked at 124,842 births in rural Colorado between1996-2009 and found that CHDs increased with increasing density of oil and gas wells around the maternal residence. Another study in Oklahoma that looked at 476,000 births found positive but imprecise associations between proximity to oil and gas wells and several types of CHDs.

Those studies had several limitations including not being able to distinguish between well development and production phases at sites, and they did not confirm specific CHDs by reviewing medical records.

The limitations were addressed in this latest study. Researchers were able to confirm where the mothers lived in the first months of their pregnancy, estimate the intensity of well activity and account for the presence of other air pollution sources. The CHDs were also confirmed by a medical record review and did not include those with a known genetic origin.

"We observed positive associations between odds of a birth with a CHD and maternal exposure to oil and gas activities...in the second gestational month," the study researchers said.

The study data showed higher levels of CHDs in rural areas with high intensities of oil and gas activity as opposed to those in more urban areas. McKenzie said it is likely that other sources of air pollution in urban areas obscured those associations.

Exactly how chemicals lead to CHDs is not entirely understood. Some evidence suggests that they may affect the formation of the heart in the second month of pregnancy. That could lead to birth defects.

McKenzie said the findings suggested but did not prove a causal relationship between oil and gas exploration and congenital heart defects and that more research needs to be done.

"This study provides further evidence of a positive association between maternal proximity to oil and gas well site activities and several types of CHDs," she said. "Taken together, our results and expanding development of oil and gas well sites underscore the importance of continuing to conduct comprehensive and rigorous research on health consequences of early life exposure to oil and gas activities."

Diabetes confers a greater excess risk of heart failure in women than men, according to new research in Diabetologia (the journal of the European Association for the Study of Diabetes). Type 1 diabetes is associated with a 47% excess risk of heart failure in women compared to men, whilst type 2 diabetes has a 9% excess risk of heart failure for women than men.

It is now recognised that diabetes and heart failure (whereby the heart pumps blood less efficiently) are conditions that often occur together. Diabetes is not only associated with an increased risk of heart failure, but also with an increased risk of death following diagnosis; and heart failure is the second most common initial presentation of cardiovascular disease in people with type 2 diabetes - more common than heart attack or stroke. The number of people with heart failure is expected to rise, making earlier prevention and treatment essential.

Accumulating evidence suggests that there are considerable sex differences in the increased risk of a range of cardiovascular diseases associated with diabetes. Previous analyses have shown that diabetes confers a greater excess risk of coronary heart disease (CHD) and stroke, as well as of other non-cardiovascular complications including dementia and cancer, in women compared with men. This study, by Dr Toshiaki Ohkuma from the George Institute for Global Health at the University of New South Wales, Sydney, Australia and Dr Sanne Peters from The George Institute for Global Health at the University of Oxford, UK, with colleagues, examined possible sex differences in the excess risk of heart failure associated with diabetes.

The study included observational cohort studies from the PubMed database if they provided sex-specific risk information of the association of diabetes with heart failure in both sexes, and excluded them if they included individuals with underlying diseases, had data for one sex only, or did not take into consideration possible confounders including at least age. The study pooled the sex-specific relative risks and the women to men ratio of relative risks for heart failure, either fatal or non-fatal, comparing individuals with diabetes to those without the condition, from the relevant research identified.

Of 5991 articles originally identified, 14 studies provided useable data for sex differences in the association between diabetes and the risk of heart failure. Two of these included data on type 1 diabetes - 2 cohorts providing results for 3,284,123 individuals and 95,129 events. Data on type 2 diabetes and heart failure were available from 13 studies, involving 47 cohorts that included 11,925,128 individuals 249,560 heart failure events.

Type 1 diabetes was associated with a 5.15 times higher risk of heart failure in women, and a 3.47 times higher risk in men - meaning a 47% excess relative risk of heart failure for women compared to men. Type 2 diabetes was associated with a 1.95 times higher risk of heart failure in women, and a 1.74 times higher risk in men - meaning a 9% excess relative risk of heart failure for women compared to men.

The authors suggest several potential explanations for the increased excess risk of heart failure in women with diabetes. Firstly they note that diabetes may confer a higher risk of CHD in women than men - CHD is a major cause of heart failure in people with type 2 diabetes and excess risk of CHD associated with diabetes has previously been shown to be greater in women. Secondly, sex differences in diabetes management could underpin these associations, as historically women have had poorer blood sugar control than men.

Another possibility is that under-treatment for women with diabetes may contribute to the development of diabetic cardiomyopathy (disease of the heart muscle causing it to become thick or rigid.

Another potential cause for the difference concerns variation in prolonged high blood sugar levels prior to full diabetes diagnosis, known as 'prediabetes', between men and women. This period can be up to two years longer in women and is associated with cardiac dysfunction. Finally, other cardiovascular risk factors, again reported to be higher in women with diabetes than men, may account for the greater excess risk in women.

In terms of type of diabetes, the excess risk in women was seen to be higher for type 1 compared to type 2. The reason for this difference is unclear, but the authors suggest it may be partly explained by the above mentioned sex differences in the association between diabetes and CHD. In a previous study the authors noted a stronger sex difference for type 1 diabetes than type 2 in the association with CHD.

The strengths of the current study include the large number of participants - data from 14 studies, with 47 cohorts and over 12 million individuals - and the fact that single sex studies were excluded. Limitations, the authors suggest, include the possibility of unmeasured confounding factors in the studies used, and the fact that potentially useful data on duration of diabetes, blood sugar control, use of glucose lowering drugs or type of heart failure was unavailable. Also, the risk of premature death is higher in men with diabetes than women with diabetes (and also in the general population), making men less likely to develop heart failure.

The excess risk of heart failure following a diagnosis of diabetes is high in both sexes, but significantly greater in women than men, conclude the authors, "highlighting the importance of intensive prevention and treatment of diabetes for women as well as men." They stress the need for further research - to understand the mechanisms underpinning this excess risk in women (particularly for type 1 diabetes) and "to reduce the burden associated with diabetes in both sexes."

Researchers from The George Institute for Global Health determined that this differential was greater in type 1 than type 2 diabetes. Type 1 diabetes is associated with a 47% excess risk of heart failure in women compared to men, whilst type 2 diabetes has a 9% higher excess risk of heart failure for women than men.

The findings published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) highlights the need for further sex-specific research into diabetes and how the condition can potentially contribute to heart complications.

According to the International Diabetes Federation (IDF), currently 415 million adults world-wide live with diabetes - with approximately 199 million of them being women. The IDF expects by the year 2040 around 313 million women will be suffering from the disease. Diabetes is the ninth leading cause of death in women and claims 2.1 million female lives every year, more so than men. The number one leading cause of death for women is heart disease.

"It is already known that diabetes puts you at greater risk of developing heart failure but what our study shows for the first time is that women are at far greater risk - for both type 1 and type 2 diabetes," said lead author and research fellow Dr Toshiaki Ohkuma from The George Institute.

"The increased risk of heart failure following a diabetes diagnosis is significantly greater in women than men which highlights the importance of intensive prevention and treatment of diabetes in women. Further research is required to understand the mechanisms underpinning the excess risk of heart failure conferred by diabetes [particularly type 1] in women and to reduce the burden associated with diabetes in both sexes."

Key findings:

Women with type 1 diabetes were associated with a more than 5-fold increased risk of heart failure compared with those without diabetes. For men, the risk was 3.5-fold higher.

Corresponding increases in risks for heart failure associated with type 2 diabetes were 95% in women and 74% in men.

Researchers also found that both type 1 and type 2 diabetes were stronger risk factors for heart failure in women than men.

Type 1 diabetes was associated with a 47% greater excess risk of heart failure in women compared with men.

Type 2 diabetes was associated with a 9% greater excess risk of heart failure in women than men.

Data compiled from 10 countries: Australia, US, UK, Italy, Sweden, Canada, Japan, China, Taiwan and Korea.

According to Diabetes Australia, the prevalence of diabetes is now so widespread that it has become the major health crisis of the 21st Century. It is the largest challenge facing the Australian health system with around 1.7 million sufferers nationwide. More than 119,000 Australians are living with type 1 diabetes, an autoimmune condition, whereas 1.3 million Australians are living with type 2 diabetes, the effects of which can be exacerbated by lifestyle factors such as poor diet and lack of exercise. It's estimated that the number of people suffering from diabetes globally will increase to 642 million by 2040.

Study co-author Dr Sanne Peters, of The George Institute for Global Health at the University of Oxford, said there are a number of reasons why women with diabetes are at greater risk of heart complications.

"Women were reported to have two years' longer duration of prediabetes than men and this increased duration may be associated with greater excess risk of heart failure in women" said Dr Peters. "Some major concerns are that women are also being undertreated for diabetes, are not taking the same levels of medications as men and are less likely to receive intensive care."

The IDF reports that girls and women with diabetes experience a range of challenges. Gender roles, power imbalances, socioeconomic inequalities resulting in poor diet and lack of physical activity can all influence vulnerability to diabetes. Women's limited access to health services and lack of pro-activity when it comes to seeking treatment for health problems can also amplify the impact of diabetes, particularly in developing countries.

Diabetes is one of the leading causes of cardiovascular disease, blindness, kidney failure and lower-limb amputation. In pregnancy, poorly controlled diabetes increases the risk of maternal and foetal complications. Women with type 2 diabetes also have a significantly increased risk of depression in comparison to men.

The George Institute has been leading gender specific research and has already shown women with diabetes have a significantly greater excess risk of stroke and coronary heart disease as well as the non-cardiovascular complications of dementia and cancer than men. It is currently investigating gender differences in stroke as well as other chronic diseases.

Highlights

In an analysis of information on children with kidney failure who began dialysis in the United States between 1995 and 2015, the risk of death was 1.36 times higher among children with higher kidney function at dialysis initiation.

The risk of death was even greater for children with higher kidney function who initiated treatment with hemodialysis rather than peritoneal dialysis.

In more recent years, children have been started on dialysis with higher kidney function.

Washington, DC (July 18, 2019) -- A recent analysis of U.S. data over 2 decades indicates that children with kidney failure are being started on dialysis at higher levels of kidney function. Initiating dialysis at a higher level of kidney function was linked to lower patient survival, however. The findings, which appear in an upcoming issue of JASN, suggest that asymptomatic children with kidney failure may benefit from delaying dialysis.

The optimal treatment for children with chronic kidney failure is kidney transplantation, but most children are treated with dialysis prior to receiving a kidney transplant for various reasons, including to address electrolyte problems, remove excess fluid in the body, and alleviate excessive fatigue. It's unclear whether the timing of dialysis initiation affects patients' long-term health, however.

To investigate, a team led by Elaine Ku, MD, MAS and Erica Winnicki, MD (University of California, San Francisco) analyzed information on children who began dialysis in the United States between 1995 and 2015. The researchers examined patients' level of kidney function at the time of dialysis initiation; they defined higher kidney function as an estimated glomerular filtration rate above 10 ml/min/1.73m2 and lower kidney function as 10 ml/min/1.73m2 or lower. (Kidney failure is defined as an estimated glomerular filtration rate below 15 ml/min/1.73m2).

Of 15,170 children, 4327 (29%) had higher kidney function at dialysis initiation. The risk of death was 1.36 times higher among children with higher kidney function at dialysis initiation. The risk of death was even greater for children with higher kidney function who initiated treatment with hemodialysis rather than peritoneal dialysis.

"We also found that over a 20-year period, children are being started on dialysis with higher kidney function," said Dr. Winnicki. "Understanding why children are being started on dialysis at higher kidney function is important, as concerted efforts to delay dialysis initiation in asymptomatic children could potentially be an avenue for improvement in survival based on these observational findings. In addition, delaying dialysis initiation could allow for more time for living donors to undergo workup for kidney transplantation and shorten the time that children would need to spend on dialysis."

An accompanying editorial noted that increasing rates of children starting dialysis with an estimated glomerular filtration rate above 10 ml/min/1.73m2 over the past 2 decades are concerning given the absence of any benefit. "The direct, immediate, and incontrovertible deleterious financial, psychosocial, and physical impacts of dialysis are experienced on a daily basis by clinicians, children, and their families," the authors wrote.

A global study of 12 million people has found diabetes increases the risk of heart failure and this increase is greater for women than men.

Researchers from The George Institute for Global Health determined that this differential was greater in type 1 than type 2 diabetes. Type 1 diabetes is associated with a 47% excess risk of heart failure in women compared to men, whilst type 2 diabetes has a 9% higher excess risk of heart failure for women than men.

The findings published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) highlights the need for further sex-specific research into diabetes and how the condition can potentially contribute to heart complications.

According to the International Diabetes Federation (IDF), currently 415 million adults world-wide live with diabetes - with approximately 199 million of them being women. The IDF expects by the year 2040 around 313 million women will be suffering from the disease. Diabetes is the ninth leading cause of death in women and claims 2.1 million female lives every year, more so than men. The number one leading cause of death for women is heart disease.

"It is already known that diabetes puts you at greater risk of developing heart failure but what our study shows for the first time is that women are at far greater risk - for both type 1 and type 2 diabetes," said lead author and research fellow Dr Toshiaki Ohkuma from The George Institute.

"The increased risk of heart failure following a diabetes diagnosis is significantly greater in women than men which highlights the importance of intensive prevention and treatment of diabetes in women. Further research is required to understand the mechanisms underpinning the excess risk of heart failure conferred by diabetes [particularly type 1] in women and to reduce the burden associated with diabetes in both sexes."

Key findings:

Women with type 1 diabetes were associated with a more than 5-fold increased risk of heart failure compared with those without diabetes. For men, the risk was 3.5-fold higher.

Corresponding increases in risks for heart failure associated with type 2 diabetes were 95% in women and 74% in men.

Researchers also found that both type 1 and type 2 diabetes were stronger risk factors for heart failure in women than men.

Type 1 diabetes was associated with a 47% greater excess risk of heart failure in women compared with men.

Type 2 diabetes was associated with a 9% greater excess risk of heart failure in women than men.

Data compiled from 10 countries: Australia, US, UK, Italy, Sweden, Canada, Japan, China, Taiwan and Korea.

According to Diabetes Australia, the prevalence of diabetes is now so widespread that it has become the major health crisis of the 21st Century. It is the largest challenge facing the Australian health system with around 1.7 million sufferers nationwide. More than 119,000 Australians are living with type 1 diabetes, an autoimmune condition, whereas 1.3 million Australians are living with type 2 diabetes, the effects of which can be exacerbated by lifestyle factors such as poor diet and lack of exercise. It's estimated that the number of people suffering from diabetes globally will increase to 642 million by 2040.

Study co-author Dr Sanne Peters, of The George Institute for Global Health at the University of Oxford, said there are a number of reasons why women with diabetes are at greater risk of heart complications.

"Women were reported to have two years' longer duration of prediabetes than men and this increased duration may be associated with greater excess risk of heart failure in women" said Dr Peters. "Some major concerns are that women are also being undertreated for diabetes, are not taking the same levels of medications as men and are less likely to receive intensive care."

The IDF reports that girls and women with diabetes experience a range of challenges. Gender roles, power imbalances, socioeconomic inequalities resulting in poor diet and lack of physical activity can all influence vulnerability to diabetes. Women's limited access to health services and lack of pro-activity when it comes to seeking treatment for health problems can also amplify the impact of diabetes, particularly in developing countries.

Diabetes is one of the leading causes of cardiovascular disease, blindness, kidney failure and lower-limb amputation. In pregnancy, poorly controlled diabetes increases the risk of maternal and foetal complications. Women with type 2 diabetes also have a significantly increased risk of depression in comparison to men.

The George Institute has been leading gender specific research and has already shown women with diabetes have a significantly greater excess risk of stroke and coronary heart disease as well as the non-cardiovascular complications of dementia and cancer than men. It is currently investigating gender differences in stroke as well as other chronic diseases.

Social media data can provide a population-level view of physical activity, from bowling to Crossfit, and inform future efforts to tackle health disparities.

A new study led by Boston University School of Public Health (BUSPH) researchers and published in BMJ Open Sport & Exercise Medicine used machine learning to find and comb through exercise-related tweets from across the United States, unpacking regional and gender differences in exercise types and intensity levels. By analyzing the language of the tweets, this method was also able to show how different populations feel about different kinds of exercise.

"In most cases, lower-income communities tend to lack access to resources that encourage a healthy lifestyle," says study senior author Dr. Elaine Nsoesie, assistant professor of global health at BUSPH. "By understanding differences in how people are exercising across different communities, we can design interventions that target the specific needs of those communities."

In the future, social media and other digital data could help create interventions and policies informed not just by the habits of these communities, but also by what they think of different physical activities, says study lead author Dr. Nina Cesare, a postdoctoral associate in global health at BUSPH. "We believe this work provides a step in the right direction."

The researchers used a set of AI models to find and analyze 1,382,284 relevant tweets by 481,146 Twitter users in 2,900 US counties (and get rid of false positives, like references to The Walking Dead or watching sports, or using the expression "running late"). Finally, the researchers compared tweets by men and women, and from four different regions of the country: the Northeast, the South, the Midwest, and the West.

The top exercise terms were "walk," "dance," "golf," "workout," "run," "pool," "hike," "yoga," "swim," and "bowl." Walking was the most popular activity overall, but other activities varied by gender and region. Women in the West did more intensive exercise than in any other region, while the Midwest had the most intensive exercise among men. Men did slightly more intensive exercise than women overall, and South had the biggest gender gap in exercise intensity.

Poorly funded cancers: colon, endometrial, liver and bile duct, cervical, ovarian, pancreatic and lung

Well-funded cancers: breast, pediatric, leukemia and lymphoma

All cancers with stigmatized behavior (i.e. lung cancer and smoking) are poorly funded

Underfunding of these common cancers could negatively impact research, drug development

CHICAGO --- Many of the deadliest or most common cancers get the least amount of nonprofit research funding, according to a new Northwestern Medicine study that examined the distribution of nonprofit research funding in 2015 across cancer types.

Colon, endometrial, liver and bile duct, cervical, ovarian, pancreatic and lung cancers were all poorly funded compared to how common they are and how many deaths they cause, the study found. In contrast, breast cancer, leukemia, lymphoma and pediatric cancers were all well-funded, respective to their impact on society.

The study is the first to compare nonprofit funding distribution in the United States across cancer types. It will be published July 18 in the Journal of the National Comprehensive Cancer Network.

"The goal of this study is not to divert funds away from cancers that are well-supported, but rather expand funding for other cancers that aren't getting enough support currently," said corresponding author Dr. Suneel Kamath, who was the chief fellow in the department of hematology and oncology at Northwestern University Feinberg School of Medicine when he conducted the study. "These are all deadly and life-altering diseases that deserve our attention and support."

Cancer-related nonprofit organizations play an important role in funding medical research, supporting the education of patients and their families and influencing health policy. Underfunding of these common cancers could negatively impact research, drug development and the number of FDA drug approvals for poorly funded cancers.

"Well-funded patient advocacy organizations should be applauded for their successes," said co-author Dr. Sheetal Kircher, assistant professor of hematology and oncology at Feinberg and a Northwestern Medicine oncologist. "We hope to bring awareness to the organizations with less relative funding so we can collaborate to improve funding and outcomes for all patients with cancer."

The study also explored factors that may influence which cancers receive more public support over others. Cancers that are associated with a stigmatized behavior, such as lung cancer with smoking or liver cancer with drinking, were all poorly funded.

"Shame and discomfort with talking about our bowels and 'private parts' may be reducing funding for diseases like colon or endometrial cancer," Kamath said.

The nationwide study, conducted between October 2017 and February 2018, used IRS tax records to identify all nonprofit organizations that support any type of cancer and made at least $5 million in annual revenue in 2015. The scientists examined 119 organizations with a total of $5.98 billion in annual revenue. Most of this ($4.59 billion) went to general cancer charities with no focus on one disease (e.g. American Cancer Society).

The authors compared the amount of revenue for each cancer type with the number of new cases, number of deaths and number of years of life lost to see if the amount of funding for each cancer is proportional to how common and/or deadly it is.

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL), published today in Molecular Cancer Research a study where they identify methylation patterns associated with different subtypes of breast cancer, and a subclassification of the group of "triple negatives", a breast cancer type typically associated with poor prognosis. In addition, researchers identified changes in DNA methylation associated with the response to docetaxel, a common therapy. The research was led by Dr. Eva González-Suárez, head of the IDIBELL Transformation and Metastasis research group.

Patient-derived xenografts (PDXs) are based on the implantation of tumor cells from a patient in an animal model (mice). This yields a much more representative model for drug preclinical studies compared to conventional cell cultures.

Methylation is an epigenetic way of regulating gene expression, which is based on the binding of molecules, called methyl groups, into DNA. These molecules bind to DNA following certain methylation profiles and activate or silence gene expression without altering the genetic sequence.

The authors of the study have reported for the first time that the methylation patterns of tumor samples from the two main breast cancer subtypes (with and without hormone receptors) in PDXs, are the same as those observed in patients. This fact validates the use of these models in preclinical studies of methylation and drug resistance.

In addition, authors have also observed that in triple negative breast cancer, a very heterogeneous and vaguely classifiable cancer group, there are methylation patterns that would allow subclassification. This classification in subgroups could allow researchers to find more specific treatments.

Another factor that the researchers asked was whether methylation played, in tumor cells, an important role in the acquisition of resistance to drugs such as docetaxel, one of the most widespread drugs in chemotherapy. "Even no changes in the global methylation profiles were found, we have identified changes in the methylation of specific genes that can improve the classification of patient samples, thus helping us know whether they will respond to docetaxel treatment or not", Dr. González-Suárez explains, and she adds, "the differentially methylated genes identified can help us find treatments associated with the new subgroups".

Targeting obesity through exercise and calorie restriction is often the first line of approach to treat diabetes and related cardiovascular disorders, such as cardiomyopathy. A recent animal study published in The FASEB Journal explored an alternative sirtuin-based therapy to block the development of obesity and cardiomyopathy under conditions of excess nutrition, when diet restriction and regular exercise are not feasible.

For this study, researchers assessed the potential of SIRT6 - often considered a longevity factor - to protect the heart from developing diabetic cardiomyopathy. Prior research has shown that a deficiency of nuclear sirtuin SIRT6 can lead to the development of cardiomyopathy in mice.

To conduct the experiment, researchers generated a group of whole-body SIRT6-overexpressing transgenic mice (Tg.SIRT6). The research team then observed the following groups of mice for 24 weeks: 1) control non-transgenic (N.Tg) mice fed a normal diet; 2) Tg.SIRT6 mice fed a normal diet; 3) control non-transgenic (N.Tg) mice fed a high-fat, high-sucrose (HF-HS) diet; and 4) Tg.SIRT6 mice fed a HF-HS diet.

As expected, the control N.Tg mice fed a HF-HS diet developed obesity, compared to the N.Tg and Tg.SIRT6 mice fed a normal diet. Surprisingly, however, the Tg.SIRT6 mice fed a HF-HS diet did not develop obesity. This unexpected finding demonstrated that over-expression of SIRT6 can prevent the development of obesity under the conditions of excessive nutrition.

"We believe the information presented in this study will help us understand the pathogenesis of diabetic cardiomyopathy and its progression," said Mahesh P. Gupta, MS, PhD, professor and director of the University of Chicago's Cardiothoracic Surgery Research Program. "One day, a SIRT6-based therapy would be beneficial to patients who are unable to undertake regular exercise or diet restrictions to prevent the evolution of diabetes."

"These are intriguing findings," said Thoru Pederson, PhD, Editor-in-Chief of The FASEB Journal. "We have always thought of the sirtuin pathways as impinging on 'aging' in a generic sense but of course there are specific elements and this study has uncovered one that interacts with the morbidity/mortality factors of obesity and diabetes. We now might think of a 'sirtuin syndrome.'"

Accurate and timely diagnosis of the tropic disease visceral leishmaniasis (VL) is one of the pillars for reducing VL deaths. Currently available serological tests for diagnosing VL vary widely in their performance and may, as a whole, be inadequate for VL diagnosis, researchers report in PLOS Neglected Tropical Diseases.

Visceral leischmanisis is the most severe form of leishmaniasis and is potentially fatal if not diagnosed and treated in a timely manner. Approximately 96% of the VL cases in South America are reported in Brazil, where a range of serological tests are available for diagnosis. No previous study has comparatively analyzed the performance of these tests.

In the new work, Mariana Freire of the Oswaldo Cruz Foundation, Brazil, and colleagues directly compared the performance of eight diagnostic kits on a panel of 236 stored blood samples from patients with clinically suspected VL, including 77 HIV-infected patients. The kits tested were three enzyme-linked immunosorbent assays (ELISAs), two immunofluorescence antibody tests (IFATs), two immunochromatographic tests (ICTs) and one in-house direct agglutination test (DAT-LPC).

The highest accuracy rate among non-HIV-infected patients was seen in one of the ICTs (96.2% accuracy, 95%CI: 92.8-99.7) and the DAT (95.6% accuracy, 95%CI: 91.9-99.3). For the ELISA tests, the maximum accuracy was 91.2% and for the IFATs, the maximum accuracy was 84.3%. In addition, a lower accuracy was seen among HIV-infected patients. There is no consensus about the minimum sensitivity and specificity rates required for a VL diagnostic test. If we considered the minimum sensitivity and specificity of 95% and 98% that a previous paper had laid out as necessary, none of the diagnostic tests evaluated here are satisfactory.

In this study, the authors demonstrated significant difference in the performances of different serological tests available for VL diagnosis in Brazil. "Our findings highlight the need for more stringent criteria for the registration of diagnostic products in Brazil, including the requirement to carry out validation studies before marketing," the researchers say. "In a future, broader analysis, in addition to performance, other aspects of these tests should be considered before a diagnostic strategy is defined, such as cost-effectiveness, national production/autonomy and accessibility."

ATHENS, Ohio (July 17, 2019) - The drug addiction epidemic continues to plague the country, and thousands of lives are cut short each year due to overdose. Tragically, when a person's life ends prematurely, much of their potential impact on the world is lost as well. This includes both lost benefits to society and lost experiences for family and friends left behind.

To illustrate this point, a new study from Ohio University shows that more than 1 million years of life were lost in Ohio from overdose deaths between Jan. 1, 2009 and Dec. 31, 2018.

The Ohio Alliance for Innovation in Population Health (The Alliance) -- a collaborative initiative formed by Ohio University's College of Health Sciences and Professions (CHSP), other higher education partners, health systems, insurers, policy groups and population health advocates -- recently reviewed overdose death data for the state of Ohio, including preliminary data for 2018, to determine the extent that overdose deaths contributed to premature mortality.

Data from the Ohio Department of Health's Death Certificate file was analyzed and the years of life lost (YLL) calculation was made by subtracting the age of death from the expected lifespan based on data from the Social Security Administration.

In 2009, 1,389 people died of overdose in Ohio. This number increased by approximately 200 per year before growing by around 400 in 2014, 500 in 2015 and then 1,000 in both 2016 and 2017 where it peaked at 4,817.

In total, 26,375 Ohioans died of overdose between 2009-2018; while these individuals lived a total of 1,090,964 years, they also experienced a combined 1,028,005 years of life lost -- essentially cutting their lives in half.

"The Alliance's newest study of years of life lost in Ohio reveals that the average lifespan of our state has been reduced by 0.78 years as a result of drug overdose," said Rick Hodges, director of The Alliance. "In 2017 alone, the average lifespan in Ohio dropped by 1.28 years due to overdose deaths."

Dr. Andrew Kolodny, co-director of the Opioid Policy Research Collaborative at Brandeis University, said The Alliance's study is unique because of its accurate and relatable depiction of how families are directly impacted when a friend or loved one's life is cut short due to drug overdose.

"Years of life lost captures the experience of people who have lost loves ones better than counting the number of deaths," Kolodny said. "It's the years that they won't get to experience birthdays or the years that they won't see their loved ones grow and mature. This staggering figure of a million years of life lost reflects the many young people who have died and it's hard to really conceive how much pain and suffering that figure represents."

Scott Weidle, of Germantown, Ohio, knows this pain all too well. His son, Daniel, died in 2015 after suffering from addiction, joining Weidle's stepson, nephew and brother -- all of whom died of opioid overdose between 2005 and 2018.

Weidle then created danielsstory.org, and his efforts have been focused on prescription opioid reform and increased care for persons struggling with addiction. In 2018, Daniel's Law was signed in Ohio, permitting pharmacists to administer Vivitrol to prevent the effect of opioids on the body.

"(Daniel) left behind three children, who will go on to live without their father for the rest of their lives," Weidle said. "More than all of the years of life lost, I find it most troubling to reflect on who is missing out on those years of life; the children, the families and the friends."

Germantown is located in Montgomery County, which has one of the highest YLL in the study both by population per 100,000 and total.

The Alliance's study indicates:

Cuyahoga County accounts for the highest total of YLL with 112,464. Franklin County lost 100,683 years of life and Hamilton County was followed closely by Montgomery County at 89,501 YLL and 88,869 YLL, respectively. In Southern Ohio, Ross County suffered nearly 10,000 YLL and in Northwest Ohio, Lucas County lost 37,482 years of life.

Based on a population per 100,000, Southern Ohio and Southwest Ohio were hit hardest as 12 counties in those areas had more than 11,000 years of life lost, ranging from Hamilton (11,155) to Montgomery (16,606). The remaining counties include: Adams, Pike, Fayette, Ross, Clinton, Clark, Clermont, Scioto, Butler and Brown. In Central Ohio, Marion County had 11,469 YLL and in Northeast Ohio, Trumbull County had 12,508 YLL.

The study includes additional data sets that focus on region, drug type, age, gender and race for the periods between 2009 and 2018.

"The report that over a million years of life was lost due to drug overdose in Ohio over the past decade is sobering. We need to appreciate that each year of life lost is a year that a family is missing a loved one, and our state is missing someone who didn't have the opportunity to reach their maximum potential," said Mark Hurst, medical director for the Ohio Department of Health. "At the same time, we need to emphasize that overdose deaths in Ohio have dropped recently and more people than ever are receiving effective treatment. People do recover from addiction, and we should never lose that hope and perspective."

According to Orman Hall, an executive in residence for CHSP and the study's author, Ohio's drug overdose deaths began increasing well before the years covered in this research.

"We estimate there would have been less than 20,000 years of life lost on average annually in the mid-1990s," Hall said. "In 2017, there were more than 188,000 years of life lost. That's a 900 percent increase."

Kolodny said Ohio is one of the states hardest hit in the country by the overdose and addiction epidemic. However, he said there could be positive news on the horizon, as early 2018 statistics are currently projecting a nationwide drop in opioid-related overdose deaths for the first time in 25 years.

The Alliance's study also shows a decrease in overdose deaths in 2018 (3,609) compared to 2017 (4,817). Such a projected decrease would represent 47,613 less years of life lost between the past two years.

"I don't know if that (YLL) decrease will be as dramatic nationally, but there is evidence that Ohio may be bending the curve," said Kolodny. "It looks like there was a real drop in 2018, we don't know if the trend continues in 2019, but there is some light at the end of the tunnel."

Kolodny cautioned that even with the potential decrease in overdose deaths in 2018, record numbers of overdose deaths still occur in Ohio and across the United States.

According to Kolodny, the strategies for bringing the opioid addiction epidemic to an end are not necessarily the strategies that will reduce overdose deaths in the short term because the incidence rate of opioid use disorder needs to be reduced first. He said more cautious prescribing practices are needed to prevent new cases. To reduce overdose deaths, he said the most effective strategy involves making effective treatment more easily available.

"The Alliance's research paints a sobering picture of the real-world impact of our state's drug epidemic. Not only have families lost their sons, daughters, siblings, relatives and friends, they've also lost all that they could have been had their lives not been cut short by overdose," said CHSP Dean Randy Leite. "CHSP will continue to work to address the needs of our communities and to find innovative ways to assess and address the public health needs of our society. Combatting Ohio's drug overdose epidemic will continue to be an important focus of our collective efforts."