Body

CHICAGO -- Being obese or having a higher body mass index (BMI) while carrying a BRCA (BReast CAncer gene) mutation is positively linked with higher levels of damage to the DNA in normal breast gland cells, new research suggests. The results of the study will be presented Sunday, March 18, at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

Obesity is a known risk factor for breast cancer, and breast cancer has been shown to occur more frequently in BRCA mutation carriers who are obese than in those who are lean.

"These data show for the first time that obesity is associated with increased DNA damage in breast epithelium of BRCA mutation carriers," lead study author Priya Bhardwaj, a Ph.D. student at Weill Cornell Medicine in New York, N.Y., and colleagues write in their abstract.

Bhardwaj and her colleagues analyzed archival breast tissue from 82 BRCA mutation carriers. Using immunofluorescence to stain the gamma-H2AX foci, which occur as a result of DNA damage, they examined the normal breast epithelium for DNA damage.

The researchers counted the number of gamma-H2AX foci and found a significant positive link between BMI and the number of gamma-H2AX foci in the tissue.

Obesity was positively associated with DNA damage in the breast epithelial cells of individuals whether or not they were BRCA mutation carriers, but the stronger effect was seen in the tissue of those who were BRCA mutation carriers.

"Women who carry a mutation in BRCA genes have an increased risk of developing breast and ovarian cancer," Kristy A. Brown, Ph.D., study principal investigator, said. "Obesity is a well-established risk factor for breast cancer in the general population and some studies suggest that maintaining a healthy lifestyle by exercising or avoiding obesity may decrease the likelihood of developing cancer in BRCA mutation carriers."

"This research provides biological evidence for cells of the breast being susceptible to the effects of obesity," she noted. "Maintaining a healthy weight may be associated with a decreased likelihood of developing breast cancer by limiting the amount of DNA damage in the breast glands."

CHICAGO--Breastfeeding may protect high-birthweight infants from having overweight or obesity as children, new research from South Korea suggests. The results will be presented in a poster on Sunday, March 18 at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

"High birthweight is associated with overweight or obesity during early childhood. Among high-birthweight infants, exclusive breastfeeding is a significant protective factor against overweight and obesity," said lead study author Hae Soon Kim, M.D., of Ewha Womans University College of Medicine in Seoul.

High-birthweight infants were highly likely to meet the criteria for obesity or overweight through 6 years of age compared with normal birthweight infants. But the risk of becoming overweight or obese dropped significantly among the high-birthweight infants who were breastfed for first six months of life," Kim added.

In a retrospective cohort study, Kim and co-authors, all of Ewha Womans University College of Medicine, investigated the weight-growth trajectory and the protective effect of breastfeeding for obesity in children. They analyzed data between January 1, 2008 and December 31, 2016 from the National Health Information Database (NHID) of Korea.

The researchers followed 38,039 participants who were completely eligible for all health checkups from birth through 6 years of age. At each check-up period, the authors examined the association between birthweight status and growth development.

Infants were assigned to one of three groups by birthweight: the low-birthweight group, less than or equal to 2,500 grams; the normal-birthweight group, over 2,500 grams and under 4,000 grams; and the high-birthweight group, 4,000 grams or more.

During the follow-up period, about 10 percent of the low-birthweight infants and 15 percent of the normal-birthweight developed obesity or overweight. By contrast, more than 25 percent of the high-birthweight infants met the criteria for obesity or overweight.

The high-birthweight infants were highly likely to be overweight or have obesity compared with normal birthweight infants through 6 years of age, and the low-birthweight infants were highly likely to be underweight through 6 years of age.

But the risk of overweight or obesity decreased significantly if high-birthweight infants were exclusively breastfed for the first six months of life.

"The increase in the prevalence of childhood overweight and obesity, which began in the 1970s, has grown into a global epidemic. Obesity persists from childhood to adolescence and into adulthood and is a leading cause of health problems," the authors cautioned in their abstract.

The Ministry of Health & Welfare of the Republic of Korea funded the study.

CHICAGO--Young women with premature ovarian insufficiency (POI) may be able to use their own bone marrow stem cells to rejuvenate their ovaries and avoid the effects of premature menopause, new research suggests. The preliminary results from the ongoing ROSE clinical trial will be presented Tuesday at ENDO 2018, the 100th annual meeting of the Endocrine Society, in Chicago, Ill.

"In the two participants who have completed the treatment to date, serum estrogen levels have increased as soon as 3 months after the injection of stem cells, and the effect has lasted for at least one year. Their menopausal symptoms have been alleviated, and six months after the injection of the stem cells into the ovaries, they have resumed menses," said senior author Ayman Al-Hendy, M.D., Ph.D., Professor of Gynecology and Director of Translational Research at the University of Illinois at Chicago.

The researchers plan to enroll 33 participants in their clinical trial. For the two patients who have undergone the procedure so far, they collected each woman's own mesenchymal stem cells from her posterior iliac crest bone marrow and used minimally invasive laparoscopy to inject the cells into one ovary, keeping the second, untreated, ovary as a control. The authors followed the patients closely with frequent blood work, imaging of the ovaries, menopausal symptom questionnaires, and safety studies.

Now that both women's estrogen levels have increased significantly and they have begun to menstruate, the research team looks forward to the possibility that they may again become fertile.

"Ultrasound imaging of treated ovaries shows significant size increase in the treated ovaries compared to the contralateral untreated ovaries. In the cases completed so far, the patients have tolerated the treatment very well with no complications or side effects," Al-Hendy said.

The ovaries produce hormones and eggs typically until menopause in the early fifties, when they stop working. About 1 percent of women have POI, and some are as young as in their teens, the authors wrote in their abstract.

With POI, the ovaries stop working and the women enter early menopause. They lose the ability to menstruate, ovulate and have children using their own eggs, and they may be at increased risk for menopausal symptoms including hot flushes, night sweets, mood swings and vaginal dryness, and for cardiovascular disease, osteoporosis-related fracture and earlier cognitive function decline, Al-Hendy said.

The authors are currently enrolling new participants with the goal of following more patients for a longer period.

CHICAGO--Using e-cigarettes may lead to an accumulation of fat in the liver, a study of mice exposed to the devices suggests. The research will be presented Sunday, March 18, at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

"The popularity of electronic cigarettes has been rapidly increasing in part because of advertisements that they are safer than conventional cigarettes. But because extra fat in the liver is likely to be detrimental to health, we conclude that e-cigarettes are not as safe as they have been promoted to consumers," said lead author Theodore C. Friedman, M.D., Ph.D., Chairman of the Department of Internal Medicine and Endowed Professor of Cardio-Metabolic Medicine at Charles R. Drew University of Medicine & Science in Los Angeles, Calif. "This has important public health and regulatory implications."

E-cigarettes contain nicotine, which Dr. Friedman and other researchers have reported is associated with non-alcohol fatty liver diseases. However, the long-term effects of e-cigarettes on liver disease, diabetes, heart disease or stroke are unknown.

In the 12-week study, Friedman and colleagues studied mice missing the gene for apolipoprotein E, which makes them more prone to developing heart disease and fat in the liver. All of the mice were fed a diet relatively high in fat and cholesterol. One group of mice was put in a chamber that exposed them to e-cigarette aerosol, so that their blood nicotine levels were similar to that of smokers and e-cigarette users. A second group of mice were exposed to saline aerosol.

The researchers collected liver samples, and looked at genes in the liver affected by e-cigarettes using a technique called RNA sequence analysis. They found changes in 433 genes that were associated with fatty liver development and progression in the mice exposed to e-cigarettes. The researchers also found that genes related to circadian rhythms (the body clock) were changed in mice exposed to e-cigarettes. Circadian rhythm dysfunction is known to accelerate the development of liver disease including fatty liver diseases.

"Our experimental results will provide support to policymakers and federal and state regulatory bodies to take preventive measures to stop the increasing use of e-cigarettes among both children and adults," Friedman said.

CHICAGO--Hospitalized patients with stable coronary artery disease (CAD) may need frequent glucose monitoring to prevent hypoglycemia and death, new research reports. The results will be presented in a poster on Saturday, March 17 at ENDO 2018, the annual 100th meeting of the Endocrine Society in Chicago, Ill.

"Frequently monitoring the finger-stick blood glucose levels of heart disease patients admitted to the hospital to avoid low sugar level, even among those without diabetes, could potentially save lives and decrease length of hospital stay and healthcare costs," said lead study author Shuyang Fang, M.D., a medical resident at Mount Sinai St. Luke's and Mount Sinai West hospitals, in New York, N.Y.

"In hospitalized patients with coronary artery disease, hypoglycemia episodes are associated with increased hospital stay, healthcare expenses and death . . . In this study using national inpatient data, we found that those who had stable coronary artery disease and were admitted to the hospital for various reasons would have higher mortality if they developed low blood glucose levels during their hospital stay," he explained. "Interestingly, these effects were particular higher among patients without preexisting diabetes."

Fang and his colleagues at Mount Sinai used the National Inpatient Sample (NIS) database to conduct a nationwide retrospective cohort study of patients admitted to acute care hospitals in the United States with stable coronary artery disease in 2014.

Of the 1,262,943 patients admitted with stable coronary artery disease that year, about 3,000 (0.24 percent) had an episode of hypoglycemia during their inpatient stay. Compared to patients without hypoglycemia, those with hypoglycemia were more likely to be female (39 percent vs 47 percent, respectively), live in poverty (29 percent vs 34 percent), and have certain features of renal failure (27percent vs 32 percent) and heart failure (20 percent vs 27 percent). But they were less likely to have diabetes (10 percent vs 32 percent).

Compared to patients without hypoglycemia, those with hypoglycemia had higher inpatient mortality (OR 4.48), longer hospital stays (mean 5.3 vs 7.0 days), and higher healthcare costs (US $57,275 vs $70,957).

After adjustments for age, sex, race, income and clinical factors including diabetes, heart failure and kidney failure, the associations for mortality, length of stay and healthcare costs remained significant.

CHICAGO--A telehealth program for diabetes self-management not only shortens the wait to talk to a physician specialist versus an in-person visit but also results in patients with type 2 diabetes having comparable improvements in blood glucose (sugar) control to patients receiving traditional care, a study conducted in veterans finds. Results of the late-breaking abstract will be presented Saturday at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

The "telediabetes" program at the Veterans Affairs (VA) Pittsburgh Healthcare System, where the study took place, merges an electronic consultation, or e-consult, from an endocrinologist specializing in diabetes with ongoing telephone-based care, said Archana Bandi, M.D., the study's senior investigator and the clinical director of Telehealth Services for VA Pittsburgh Healthcare System. Unlike a typical e-consult meant to be a one-time recommendation, this program provides team-based care with follow-up, she noted.

"Without incurring any travel, our electronic consultation program provides equally efficacious diabetes care with significantly expedited access," Bandi said. "This type of e-consult is a viable alternative to traditional face-to-face care delivery, especially in remote areas with a shortage of endocrinologists."

For the e-consult, Bandi said an endocrine provider reviews the patient's medical record and conducts a 20- to 30-minute phone interview with the patient and family, before electronically sending the referring physician recommendations to share with the patient on lowering his or her blood sugar levels. A nurse on the diabetes care team monitors the patient's progress via phone calls over the next three to six months. The primary care provider obtains all needed laboratory tests and makes recommended changes in therapeutic regimen. Patients are also offered ancillary services such as nutrition counselling and diabetes education services close to home.

In this study, Bandi and her research team compared results for 442 patients who participated in the e-consult program and another 407 patients who had a traditional face-to-face visit and follow-up care. All patients were veterans with type 2 diabetes who were referred from remote VA facilities between 2010 and 2015 for a consultation about improving their blood sugar control.

Veterans in the e-consult group, compared with the face-to-face group, were several years younger on average (64 versus 68 years), slightly more likely to be male (98 versus 95 percent) and more often lived in a rural area (16 versus 4 percent), the investigators found. At the initial consult, both groups reportedly had a hemoglobin A1c--a measure of average blood glucose level over the past few months--of 10 percent.

The time to obtain a face-to-face consultation took 37 days, compared with only 10 days for an e-consult, according to the study abstract. Within three to six months of the consultation, patients in both groups significantly improved their A1c, which was just under 9 percent for the e-consult group and 8.75 percent for the face-to-face group. One year after the consult, A1c improved further in each group, to 8.8 percent in the e-consult group and 8.6 percent in the face-to-face group. In the e-consult group, the decline in A1c differed by the level of the veterans' engagement in self-care of their diabetes, with the patients who fully engaged in adhering to the recommended treatment having the lowest A1c at one year (8.6 percent), Bandi said.

"Given the obesity and diabetes epidemic along with the current shortage of endocrinologists in the U.S., the care delivery for patients with diabetes needs a complete change in its paradigm," she said. "An example is our innovative model of care delivery that brings quality care to the patient's doorstep in an expedient fashion."

CHICAGO--Patients undergoing Roux-en-Y gastric bypass (RYGB) surgery may be at greater risk for non-vertebral fracture than those having adjustable gastric banding (AGB), a new population-based study reports. The results will be presented on Saturday, March 17 at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

"Bariatric surgery procedures, such as RYGB, are highly effective treatments that induce sustained weight loss," said lead study author Elaine Wei-Yin Yu, M.D. "RYGB leads to greater improvements in metabolic health than AGB, but RYGB also causes accelerated bone loss and may increase fracture risk."

"We found that Medicare patients who received RYGB had more fractures compared to those who received AGB. Importantly, we found that RYGB increased the risk for hip, wrist, and pelvis fractures. RYGB increased fracture risk across all age groups, in men and in women, although the effects were more pronounced among men," said Yu, assistant professor of medicine at Harvard Medical School and director of the Bone Density Center at Massachusetts General Hospital, in Boston, Mass.

Yu and her colleagues investigated the fracture rates among Medicare Parts A, B and D enrollees with severe obesity who underwent either RYGB or AGB surgery between 2006 and 2014.

The researchers analyzed Medicare billing claims data from 50,649 adults (78 percent women). Of these, 35,920 underwent RYGB and 14,729 underwent AGB. The authors compared fracture rates between the two groups, controlling for differences in age, sex, race, geographical location, index date, degree of healthcare utilization, comorbidities, and prescribed medications.

RYGB patients were younger than AGB patients (53 vs 56 years of age), and they were more likely to have diabetes (36 percent vs 32 percent) as well as a shorter average follow-up time (3.1 vs 3.8 years).

A total of 1,109 non-vertebral fractures were reported during follow-up. The estimated incidence rates of non-vertebral fractures per 1,000 person-years were 9.8 in the RYGB group and 7.1 in the AGB group. Age or diabetes status did not affect RYGB-associated fracture risk.

Compared with patients who received banding, those who underwent bypass had a 126 percent increased risk of hip fracture, a 62 percent increased risk of wrist fracture, and a 172 percent increased risk of pelvis fracture. Gastric bypass increased overall fracture risk more dramatically in men (108 percent) than in women (42 percent).

"This research is very relevant given the high prevalence of obesity and increasing utilization of bariatric surgery. Over one-third of adults in the United States are obese, and bariatric surgery procedures have accordingly been increasing in popularity," Yu said. "Long-term skeletal health should be discussed and managed for all patients undergoing bariatric surgery. . . These data also emphasize the importance of devising therapies that can counteract fracture risk after gastric bypass."

CHICAGO--Giving one year of estrogen replacement to female athletes with exercise-induced menstrual irregularities improves drive for thinness, body dissatisfaction and uncontrolled eating, a new study finds. The research results will be presented Saturday, March 17, at ENDO 2018, the annual scientific meeting of the Endocrine Society, in Chicago, Ill.

"Female athletes with exercise-induced menstrual dysfunction (associated with low estrogen levels) often have disordered eating behavior, which may impact their reproductive and bone health," said lead researcher Madhusmita Misra, M.D., M.P.H., professor of pediatrics at Harvard Medical School and a pediatric endocrinologist at Massachusetts General Hospital in Boston, Mass.

"Our findings underscore the relationship between estrogen and disordered eating behavior, and the potential of estrogen replacement as a treatment target, not just in athletes, but potentially also in other conditions characterized by abnormal eating behavior and frequent menstrual dysfunction, such as anorexia nervosa," she said.

Her study found that female athletes with exercise-induced irregular menstrual periods report more disordered eating behavior than athletes and non-athletes getting regular periods. "In particular, female athletes tend to restrain their eating, display a stronger desire to become or stay thin, and have a higher level of dissatisfaction with their bodies compared to athletes and non-athletes with normal menstrual cycles," she said.

Misra compared 109 female athletes with exercise-induced menstrual irregularities with 50 female athletes with normal menstrual cycles and 39 female non-athletes. All of the study subjects were 14-25 years old and were in a normal weight range. The young women's eating behavior and mental health was evaluated with self-report assessments and questionnaires.

Athletes with irregular periods reported a higher drive for thinness and more mental control over their food intake compared with athletes with regular periods and non-athletes. They also had higher mean body dissatisfaction scores than athletes with regular periods.

Athletes who had irregular menstrual periods were randomly assigned to receive either estrogen replacement through a patch, at a dose that resulted in estrogen levels seen with normal menstrual cycles; a commonly used combined oral contraceptive pill containing estrogen; or no estrogen for 12 months. Athletes randomized to estrogen replacement as a patch also received cyclic progesterone.

Over one year, the groups that received estrogen showed reductions in drive for thinness, body dissatisfaction and uncontrolled eating, compared with those who didn't receive estrogen. The patch was the most effective, leading to significant decreases in body dissatisfaction and uncontrolled eating.

"These results highlight the importance of normalizing estrogen levels in female athletes with irregular menstrual periods," Misra said. "This not only improves their bone health (as we have previously reported), but may also improve their eating behavior. More studies are necessary to confirm these findings."

The heart is the first organ to develop in the womb and the first cause of concern for many parents.

For expecting mothers, the excitement of pregnancy is often offset by anxiety over medication they require. Parents and doctors often have to consider the mother's health as well as the potential risk regarding how medication could affect their baby. The U.S. Food and Drug Administration requires certain drugs to be labeled with pregnancy exposure and risk. Some drugs are labeled to show that testing on animals has failed to demonstrate a risk but there are no adequate and well-controlled studies of pregnant women.

"Some drugs are difficult for doctors to prescribe to pregnant women because they don't know the embryo toxicity, how does that effect fetal development," said biomedical engineering Professor Zhen Ma. "They don't have the clinical outcome based on human study."

Ma and his research team in Syracuse University's System Tissue Engineering & Morphogenesis (STEM) lab have been working with human induced pluripotent stem cells to study tissue regeneration, regenerative medicine and stem cell engineering.

"This type of stem cell has the ability to generate all the different cells in a human body. Because it was derived from humans," said Ma.

Pluripotent cells can be used to create heart tissue but Ma's research team believed they could take it even further.

"We can try to rebuild the shape of the early development heart in the lab," said Ma. "It mimics the very early stage, during the embryo genesis - how the heart was formed."

Ma's research team developed a process that combines biomaterials-based cell patterning and stem cell technology to make a 3D tissue model that could mimic early stage human heart development. By starting with a layer of polymer in a tissue culture dish and etching tiny patterns in the polymer, the stem cells will only attach within those patterns. Since the stem cells do not attach to the polymer, they grow within the patterns and eventually develop into a three-dimensional structure that has distinct tissue types. The process developed by Ma's team focused on cardiac tissue but other labs could adapt it to other tissue types and even organ tissues.

Their research will be published in the March 2018 Nature Protocols journal and featured on the cover.

The platform allows tissue to form during the cell differentiation process rather than building tissue out of already established heart cells. Tissue that forms during the differentiation process has more layers and more accurately represents how tissue naturally develops in humans.

"Using the cell lines we use, they are human based so we know they will affect human tissue in a certain way as opposed to the uncertainty that comes with an animal model," said graduate student Plansky Hoang.

Some pregnant women avoid taking drugs they need to manage chronic conditions but if the mother's health suffers, that can also affect her baby. More reliable test results could provide more confidence for both patients and doctors.

"It helps people make better decisions," said Ma. "If we can determine it is safe, it should be prescribed to women who need these drugs."

Embryotoxicity is just one potential use of the modeling platform developed by Ma and his team. Countless other human tissues could also be cultured using the process. It could also allow for individualized drug toxicity testing for humans. Different people can have different reactions to the same drug but personalized testing using someone's stem cells could help determine if a drug is safe for them before they take it.

"The traditional way of screening, they take a patient history and then test you on a drug for a month or two and they assess again you after that," said Hoang. "By using our model we can test for multiple drugs at once so if there is a series of drugs that will potentially benefit you, we can test all of them at once as opposed to one at a time that takes longer."

Pyruvate kinase (PK), an omnipresent and functionally important enzyme, catalyzes the conversion of ADP and phosphoenolpyruvate (PEP) to ATP and pyruvate. The reaction, physiologically irreversible, is a key step in glycolysis, responsible for the final substrate level phosphorylation step. Pyruvate and PEP are also key metabolites that act as precursors for various biosynthesis pathways.

Enzyme cycling provides the means to enhance the sensitivity of enzyme detection systems by amplifying the signal. We have developed a novel enzymatic cycling method mediated by PK from rabbit muscle (RMPK) for the quantitative determination of pyruvate or PEP, which utilizes the reversibility of the reaction in the presence of an excess amount of ATP and IDP. The production rate of ADP or ITP was proportional to the concentration of the substrate. Real-time detection of ADP production was accomplished by including ADP-dependent glucokinase (ADP-GK) from Pyrococcus furiosus and glucose-6-phosphate dehydrogenase as auxiliary enzymes. The limit of detection was estimated as 12 nM of PEP.

Unexpectedly, we observed approximately a 10-fold greater reaction efficiency with Mn2+ over that with Mg2+. However, our results from steady-state kinetics do not explain the differences observed between Mg2+ and Mn2+. It is also surprising that the efficiency of RMPK cycling with Mn2+ was much greater than that of creatine kinase from the same origin which we have previously reported, considering the greater preference of PK for the forward reaction (pyruvate forming).

ADP-GK, one of the auxiliary enzymes, is inactive towards IDP and GDP, so the method should be applicable to other kinases that accept either IDP or GDP.

For more information, please visit: http://www.eurekaselect.com/158526

PHILADELPHIA -- Cities experienced 2.3 more assaults than average on days when hosting presidential campaign rallies for Donald Trump during the lead-up to the 2016 United States Presidential Election, according to a first of its kind study published online today in Epidemiology by researchers in the Perelman School of Medicine at the University of Pennsylvania. Hillary Clinton rallies were not linked to any increase in assaults, they found.

"News media sources reported there were violent incidents at some campaign rallies, but it was difficult to gauge whether there really was a systematic problem, and if so, how many additional assaults were associated with each rally," said the study's lead author, Christopher Morrison, PhD, MPH, a fellow in Penn's Center for Clinical Epidemiology and Biostatistics and an epidemiologist in the Penn Injury Science Center. "To prevent similar violence in the future, it is important to understand the underlying causes of this behavior, perhaps including the role that political rhetoric might play in normalizing or promoting violence."

Focusing on cities of greater than 200,000 people, the team performed a systematic Google search and found publicly available data for 31 rallies in 22 cities for Trump and 38 rallies in 21 cities for Clinton. Using assault data from police departments in those cities, including aggravated assaults, simple assaults, and/or battery, the team counted assaults on the day of each rally. For comparison, they also counted assaults on corresponding days of the week for four weeks before and four weeks after each rally.

Rallies in the study were defined as open invitation events that occurred after Donald Trump and Hillary Clinton declared their candidacies in spring 2015 and before the U.S. Presidential Election on November 8, 2016, featured a speech by Trump or Clinton, and were not on the same day as a party primary election in the same state as the rally.

The researchers suggest two possible explanations for their findings. First, all additional assaults could have occurred in and around the venues of candidate Trump's rallies where people invested in the process gathered. This explanation is consistent with news media reports that violence occurred at these specific locations. Second, additional assaults that took place might have occurred elsewhere in the rally cities. Studies informed by theories of social contagion find evidence that emotional states can be transmitted through news reports and digital social media, which could have led to more assaults occurring away from the rally sites.

The researchers note that Trump rallies were widely broadcast and discussed through news reports and digital social media, such as a rally in Cedar Rapids, Iowa during which candidate Trump remarked that he would "knock the crap out of" would-be hecklers at the event, and other examples from the non-partisan POLITIFACT.

"This research provides evidence that this increase in assaults is associated with candidate Trump's rallies leading up to the election," said senior author Douglas Wiebe, PhD, an associate professor in Epidemiology. "Violent language may have affected the mood and behavior of rally attendees, as well as those exposed to the rally through news reports and social media."

The researchers added that weather can also influence crime rates, so the team consulted National Oceanic and Atmospheric Administration data for the weather station nearest to each study city to control for temperature and precipitation.

Copenhagen: Scientists have found that a drug connected with fat regulation prevents the formation of kidney stones in mice. This early work opens the possibility of developing drugs which may help prevent kidney stones in at-risk individuals. The work is presented at the European Association of Urology Conference in Copenhagen.

Passing a kidney stone in the urine can be extremely painful - it has been described as possibly the worst pain which someone can experience. The developed world is experiencing something of an epidemic of kidney stones. The EAU estimates that around 50 to 60million Europeans suffer from stones - that's roughly one European in 11, and is equivalent to the population of a large European country, such as the UK, France or Italy. The USA has a similar number of sufferers. Stone incidence has almost doubled over the last 20 years1. Doctors think that this increase is due to increasing obesity, and diet and lifestyle changes.

Now a group of Japanese scientists have discovered that an experimental drug leads to a significantly reduced number of kidney stones in mice. They gave 20 mice 1mg/kg of the β3- agonist CL316243 for 12 days. Then the mice, plus 20 controls, were then injected with glyoxylate, which causes the formation of kidney stones. At various time points, the mice were then checked to see if they had formed stones: the formation of stones decreased to 17.0% in the experimental group, compared with the controls.

"This is experimental work for now" said lead researcher Dr Teruaki Sugino (Nagoya City University Graduate School of Medical Sciences, Japan). "But I believe that this may open the way to the development of the new drugs which can stop the development of kidney stones in at-risk people. So far we have only tested this on mice, but in mice it seems to work".

"We were able to analyse the biochemical differences between the control and experimental group, and discovered that the β3-agonist reduced the expression of adipocytokine molecules, which are associated with inflammation".

The researchers believe that free fatty acids cause inflammation and cytotoxic effects in kidneys, which promotes stones. β3-agonists are known to cause white fat cells (which are found in excess in overweight and obese persons) into beige fat cells, which burn extra calories, which is why these molecules are also being considered for anti-obesity uses. The researchers suspect that beige cells consume free fatty acids, which may be the cause of inflammation in the kidneys leading to kidney stones. This means that β3-agonists have the potential to prevent not only obesity but also kidney stones.

Commenting, Professor Thomas Knoll (Universität Tübingen, Germany) said:

"Renal stones affect many people, and have a high economic impact, so it's a pity that we still have an only rudimentary understanding on why stones form. Metabolic factors definitely play an important role and this work, contributes to unravelling the pathogenesis. We've had decades of urine crystallization studies, which have not really advanced the field. I hope that this work leads to more researchers doing work on the topic.

(Professor Knoll was not involved in this work, this is an independent comment).

Currently, potassium-sodium citrate drugs are used to restrict the development of kidney stones, but some people can't use these drugs because they need to limit their potassium or sodium intake.

The authors note the limitations of the study. It is animal work, so cannot yet be directly applied to humans. The molecule has not been tested for tolerability, efficacy, or cost. It is also an initial 'proof-of-concept' study, so needs to be repeated with a larger sample size.

Highlights

In a study of Black Americans who participated in focus group sessions, certain participant factors--such as knowledge of kidney disease and spiritual and cultural influences--and logistical factors--such as convenience and awareness of scheduling--were identified as barriers that may prevent Black Americans from being screened for kidney disease.

Black Americans are at increased risk of developing chronic kidney disease and kidney failure.

Washington, DC (March 15, 2018) -- The incidence of kidney failure is 3 times higher in Black Americans than in whites, and the prevalence of chronic kidney disease (CKD) continues to rise among Black Americans while it has stabilized in other racial groups. New research points to potential barriers that may prevent Black Americans from being screened for kidney disease. The findings, which are published in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN), may help guide efforts to address important kidney-related disparities in the United States.

A common strategy to promote awareness of a health condition and to identify individuals at risk is community-based health programs. To identify Black Americans' perspectives of barriers and facilitators of community-based screening for CKD, a team led by Kerri Cavanaugh, MD, MHS and Ebele Umeukeje, MD, MPH (Vanderbilt University Medical Center) performed 3 focus groups of adults in Black American churches in Nashville, Tennessee. Questions examined views on CKD information, access to care, and priorities of kidney disease health.

In the study of 32 Black Americans who participated in focus group sessions, 2 major categories of barriers to kidney disease screening were apparent: participant factors including limited kidney disease knowledge, spiritual/religious beliefs, and culture of the individual; and logistical factors including lack of convenience and incentives, and poor advertisement.

"In particular, trust and effective communication appear to be novel influential themes for achieving optimal participation of Black Americans in kidney disease screening events," said Dr. Umeukeje. "Therefore, culturally sensitive education and stakeholder engagement are likely effective strategies to improve communication, build trust, minimize fear, maximize participation in kidney disease screening events, and ultimately improve outcomes in Black Americans at risk of kidney disease."

Dr. Umeukeje noted that the low trust among Black Americans extended beyond the well-known mistrust of research and healthcare practices to include mistrust of certain aspects of community-based screening practices. "For instance, there was mistrust of urine collection because of a concern that it may be used for drug screening instead of detection of protein in urine, which is a marker of kidney disease," she said. "Additionally, spirituality among Black Americans and the notion that self-care is really God's responsibility was also found to discourage some people from embracing kidney disease screening practices."

Stigma associated with a kidney disease diagnosis and the explicit fear of being diagnosed with a condition that could lead to dialysis was a significant concern. Interestingly, there was concern from men about being labeled with a diagnosis that would force them to assume a 'sick role', which they felt would challenge their manhood, or the need to take medications that might decrease their libido. Many people admitted that incentives such as gift items, free food, and entertainment would encourage participation in kidney disease screening programs.

In an accompanying editorial, Keith Norris, MD, PhD and Susanne Nicholas, MD, MPH, PhD (David Geffen School of Medicine at UCLA) noted that the study provides a timely and well-balanced set of recommendations capturing key barriers and facilitators to consider in advancing CKD screening. "Ongoing authentic engagement with respect and partnership can help to attenuate the mistrust and activate African American communities to take a more proactive stand on their health," they wrote.

The idea that it might be possible to be overweight or obese but not at increased risk of heart disease, otherwise known as the "obesity paradox", has been challenged by a study of nearly 300,000 people published in in the European Heart Journal [1] today (Friday).

This latest research shows that the risk of heart and blood vessel problems, such as heart attacks, strokes and high blood pressure, increases as body mass index (BMI) increases beyond a BMI of 22-23 kg/m2. Furthermore, the risk also increases steadily the more fat a person carries around their waist.

The study was conducted in 296,535 adults of white European descent who are taking part in the UK Biobank study, and who were healthy at the time they enrolled with the study. UK Biobank recruited from 2006 to 2010, and follow-up data on participants were available up to 2015 for this latest analysis.

Researchers at the University of Glasgow (UK) led by Dr Stamatina Iliodromiti, a clinical lecturer in obstetrics and gynaecology and MRC Fellow, found that people with a BMI between 22-23 kg/m2 had the lowest risk of cardiovascular disease (CVD). As BMI increased above 22 kg/m2, the risk of CVD increased by 13% for every 5.2 kg/m2 increase in women and 4.3 kg/m2 in men.

Compared to women and men with waist circumferences of 74 and 83 cm respectively, the CVD risk increased by16% in women and 10% in men for every 12.6 cm and 11.4 cm increase in waist circumference for women and men respectively. Similar increases in CVD risk were seen when the researchers looked at waist-to-hip and waist-to-height ratios and percentage body fat mass - all of which are considered reliable ways to accurately gauge the amount of fat a person carries, also known as adiposity.

Although it is already known that being overweight or obese increases a person's risk of CVD, as well as other diseases such as cancer, there have also been studies that have suggested that, particularly in the elderly, being overweight or even obese might not have any effect on deaths from CVD or other causes, and may even be protective, especially if people maintain a reasonable level of fitness. This is known as the "obesity paradox".

However, the authors of the EHJ study say their results refute these previous, conflicting findings. "Any public misconception of a potential 'protective' effect of fat on heart and stroke risks should be challenged," said Dr Iliodromiti.

She continued: "This is the largest study that provides evidence against the obesity paradox in healthy people. It is possible that the story may be different for those with pre-existing disease because there is evidence that in cancer patients, for instance, being slightly overweight is associated with lower risk, especially as cancer and its treatments can lead to unhealthy weight loss.

"By maintaining a healthy BMI of around 22-23 kg/m2, healthy people can minimise their risk of developing or dying from heart disease. In terms of other adiposity measures, the less fat, especially around their abdomen, they have, the lower the risk of future heart disease."

However, the researchers recognise that it can be difficult for some people to maintain a BMI of 22-23 kg/m2, particularly as they get older. Co-author, Naveed Sattar, Professor of Metabolic Medicine at the University of Glasgow, said: "We know many cannot get to such low BMIs so the message is, whatever your BMI, especially when in the overweight or obese range, losing a few kilograms or more if possible, will only improve your health. There are no downsides to losing weight intentionally and the health professions needs to get better at helping people lose weight."

The researchers say their findings may have implications for guidelines on preventing and managing cardiovascular disease.

"Even within the normal BMI category of between18.5-25 kg/m2, the risk of CVD increases beyond a BMI of 22-23 kg/m2. The other adiposity measures show that the leaner the person the lower the risk of CVD, and this must be a public message, that healthy individuals should maintain a lean physique to minimise their risk of CVD," concluded Dr Iliodromiti.

The researchers suggest that the previous confusion over the "obesity paradox" may be due to many factors that can confound results of studies. For instance, smoking changes the distribution of fat in the body, smokers may have lower weight as smoking depresses appetites and so BMI tends to be lower. Another reason could be that some people have existing but undiagnosed disease, which can often lower their weight but also makes them more likely to die prematurely.

Girls who start puberty earlier are more likely to be overweight as adults, finds new research from Imperial College London.

The researchers say their findings, published today in the International Journal of Obesity, strengthen existing evidence of a link between the onset of puberty and a woman's body mass in adulthood.

Previous studies have established a link between obesity and puberty, with increased bodyweight known to be a risk factor for girls starting puberty earlier.

However, these observational findings can be influenced by situational factors, such as ethnicity, economic background, education level, and diet, making it difficult to determine whether early puberty or these other factors are the cause.

But now this latest research shows that early puberty is itself a risk factor for being overweight, with girls who have their first period earlier more likely to have a higher Body Mass Index (BMI).

According to the authors of the study, their findings help to untangle these complex external factors and add insight into an underlying causal link, showing that early puberty has a significant impact on a woman's risk of obesity.

Dr Dipender Gill, a Wellcome Trust Clinical Research Fellow in the School of Public Health and first author of the study, said: "Previous studies have shown there is an association, but we didn't know whether early puberty caused obesity in adulthood, or was simply associated with it. In our latest study we've generated evidence to support that it is a causal effect."

In order to get around the effects of confounding factors, the Imperial team used genetic variants as a tool to look at the effect of the onset of puberty (known as age at menarche), measured as the age of a girl's first period.

The genes in every cell of our bodies are randomly gifted to us from our parents when their sperm and egg cells fuse, with the outcome of this random jumble being the genetic basis of the embryo - influencing everything from hair colour to risk of disease for the rest of your life.

But single 'letter' changes to the DNA sequence of a gene can alter its function. In terms of disease risk, these single letter variants (called single-nucleotide polymorphisms, or SNPs) can result in a small increase or decrease in risk. The combination of variants of more than 20,000 genes contribute towards our cumulative genetic risk.

In the latest study, researchers employed a statistical technique called Mendelian Randomization which uses these genetic variants as a tool to show the causal relationship between earlier puberty and increased BMI.

Using data from 182,416 women they identified 122 genetic variants that were strongly associated with the onset of puberty - with the women's age at first period obtained via questionnaire.

The team then looked at data from the UK Biobank, which holds biomedical information on hundreds of thousands of people, incorporating physiological measurement data with genetic sequence data and questionnaire responses. Specifically, they looked for the effect of the genetic variants related to age at menarche with BMI in a second set of 80,465 women from the UK Biobank, for whom they also had measurements for BMI.

Initial analysis revealed a link between these genetic variants and BMI, with those women who had variants associated with earlier puberty having an increased BMI. The researchers then tested for this same association in a third group 70,962 women, finding the same association.

Dr Gill, added: "Some of these genetic variants are associated with earlier puberty and some with later onset, so by taking advantage of this we were able to investigate any association of age at menarche with BMI in adulthood.

"We're not saying that it's a genetic effect, but rather that by using these genetic variants as a proxy for earlier puberty, we are able to show the effect of earlier puberty without the impact of external factors that might confound our analysis. We performed a range of statistical sensitivity analyses to test the robustness of our findings and they remained strong through this, so within the limitations of the study design, we are confident of findings."

Previous research from the group has used the same technique to show that low iron levels are associated with an increased risk of heart disease, as well as showing that girls who start puberty earlier are likely to spend less time in education.

Future studies will use the same Mendelian Randomization approach to look at genetic variants in relation to drug targets for cardiovascular disease and stroke.

The technique is not without its limitations, and it is possible that these genetic variants could be influencing bodyweight independently of age at menarche, such as through altering metabolism or fat production. However, even after the team had removed any genetic variants that were also associated with childhood obesity (12 in total), they came to the same finding.

According to the researchers, it remains unclear how maturing earlier has a direct impact on bodyweight, but they indicate that differences between physical and emotional maturity may play a role. It could be that young women who mature earlier than their peers are treated differently or have different societal pressures than girls of the same age who have not started puberty.

Another explanation could be the physical effects of hormonal changes during puberty, such as increased fat deposition in breast tissue, which when established earlier may move them to a higher risk profile for higher BMI or obesity in later life.

"It is difficult to say that changing someone's age of puberty will affect their adult risk of obesity and whether it is something that we can clinically apply - as it would unlikely be ethically appropriate to accelerate or delay the rate of puberty to affect BMI," added Dr Gill. "But it is useful for us to be aware that it's a causal factor- girls who reach puberty earlier may be more likely to be overweight when they are older."