Culture

New diabetes drug may help people with obesity lose weight

CHICAGO--A compound that mimics a naturally occurring hormone that regulates appetite may help people who have obesity but not diabetes to lose weight, a new study suggests. The research will be presented Sunday, March 18, at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

The compound, semaglutide, has a chemical structure that is very similar to the hormone glucagon-like peptide 1 (GLP-1), which regulates both insulin secretion and appetite. In December, the U.S. Food and Drug Administration approved the semaglutide injection Ozempic as a once-weekly adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

"This randomized study of weight loss induced with semaglutide in people with obesity but without diabetes has shown the highest weight reductions yet seen for any pharmaceutical intervention," said lead author Patrick M. O'Neil, Ph.D., Director of the Weight Management Center and Professor of Psychiatry and Behavioral Sciences at the Medical University of South Carolina in Charleston, S.C.

The new study included 957 participants, 35 percent of whom were male. All participants had a body mass index (BMI) of at least 30, but did not have diabetes. They were randomly assigned to seven different groups. Five groups received different doses of semaglutide (between 0.05 mg and 0.4 mg) via injection once daily; a sixth group received a placebo, and a seventh group received 3 mg of the diabetes drug liraglutide. All participants received monthly diet and exercise counseling.

After one year, all participants receiving semaglutide had lost significantly more weight than those receiving placebo. The higher the dose participants received, the greater their average weight loss. Participants who received 0.05 mg of semaglutide daily lost an average of 6.0 percent of their body weight; the 0.1 mg group lost an average of 8.6 percent; the 0.3 mg group lost an average of 11.2 percent; and those receiving a daily dose of 0.4 mg lost an average of 13.8 percent. Those receiving liraglutide lost an average of 7.8 percent of their body weight, while those in the placebo group lost only 2.3 percent on average.

Sixty five percent of participants who received 0.4 mg of semaglutide per day lost at least 10 percent of their body weight, compared with 10 percent of those in the placebo group and 34 percent of the liraglutide group.

The most common adverse events in those taking semaglutide were mild/moderate nausea, as seen previously with GLP-1 receptor agonists.

O'Neil noted that further studies of semaglutide for obesity are underway.

Credit: 
The Endocrine Society

Hormone imbalance may explain higher diabetes rates in sleep-deprived men

CHICAGO--Studies have found an association between insufficient sleep and the development of insulin resistance, one of the factors that cause type 2 diabetes, and now researchers have discovered a biological reason for this relationship, at least in men: an imbalance between their testosterone and cortisol hormones. The study results will be presented Sunday at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

"Our highly controlled sleep study showed that even one night of restricted sleep can cause insulin resistance and that we can dampen this effect by controlling levels of these two important hormones," said senior investigator Peter Y. Liu, M.B.B.S., Ph.D., a professor of medicine with the Los Angeles Biomedical (LA BioMed) Research Institute at Harbor-UCLA Medical Center, Torrance, Calif.

Insulin resistance occurs when the body does not properly use the hormone insulin. Testosterone is the main anabolic, or muscle-building, hormone, whereas cortisol--often called the "stress hormone"--helps catabolism, or breaking down energy and fat stores for use, Liu explained. Past research shows that sleep loss reduces a man's testosterone levels and increases cortisol levels.

Liu and his fellow researchers conducted five nights of sleep studies in 34 healthy men with an average age of 33. They controlled what the subjects ate and how much they slept, giving them 10 hours of sleep the first night and restricting them to four hours of sleep the remaining nights. The study received funding from the National Institutes of Health and the Clinical and Translational Research Center at LA BioMed.

In this "crossover" study, the men served as their own controls. In one series of sleep studies, they received three medications: ketoconazole, which switches off the body's production of testosterone and cortisol; testosterone gel; and oral hydrocortisone, a synthetic form of cortisol. The doses of testosterone and hydrocortisone were in the midrange of levels that the body normally produces, according to Liu. This arm of the study was called a dual "clamp" because it stopped the body's production of these two hormones and then gave them a fixed amount of the hormones, thus clamping levels in a normal hormonal balance, he said.

In another set of experiments, the men received inactive placebos that matched the medications. The order of when they received the clamp and the placebo was random, with a two-week interval between the study conditions. The morning after the first and last nights of each part of the study, all men took the oral glucose tolerance test, in which they gave blood samples while fasting and again after drinking a sugary drink. This test result allowed the researchers to calculate each man's insulin resistance using standard measures, including the Matsuda Index.

After sleep restriction, this index reportedly showed greater insulin resistance with both the clamp and the placebo. However, Liu said this increase was significantly dampened, or less severe, with the dual-clamp, demonstrating that testosterone and cortisol reduced the negative effects of sustained sleep restriction on insulin resistance.

"Maintaining hormonal balance could prevent metabolic ill health occurring in individuals who do not get enough sleep," he said. "Understanding these hormonal mechanisms could lead to new treatments or strategies to prevent insulin resistance due to insufficient sleep."

Credit: 
The Endocrine Society

Low sperm count not just a problem for fertility

CHICAGO -- A man's semen count is a marker of his general health, according to the largest study to date evaluating semen quality, reproductive function and metabolic risk in men referred for fertility evaluation. The study results, in 5,177 male partners of infertile couples from Italy, will be presented Sunday at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

"Our study clearly shows that low sperm count by itself is associated with metabolic alterations, cardiovascular risk and low bone mass," said the study's lead investigator, Alberto Ferlin, M.D., Ph.D. He recently moved as associate professor of endocrinology to Italy's University of Brescia from the University of Padova, where the study took place in collaboration with professor Carlo Foresta, M.D.

"Infertile men are likely to have important co-existing health problems or risk factors that can impair quality of life and shorten their lives," said Ferlin, who is also president of the Italian Society of Andrology and Sexual Medicine. "Fertility evaluation gives men the unique opportunity for health assessment and disease prevention."

Specifically, Ferlin and his colleagues found that about half the men had low sperm counts and were 1.2 times more likely than those with normal sperm counts to have greater body fat (bigger waistline and higher body mass index, or BMI); higher blood pressure (systolic, or top reading), "bad" (LDL) cholesterol and triglycerides; and lower "good" (HDL) cholesterol. They also had a higher frequency of metabolic syndrome, a cluster of these and other metabolic risk factors that increase the chance of developing diabetes, heart disease and stroke, the investigators reported. A measure of insulin resistance, another problem that can lead to diabetes, also was higher in men with low sperm counts.

Low sperm count was defined as less than 39 million per ejaculate, a value also used in the U.S. All the men in the study had a sperm analysis as part of a comprehensive health evaluation in the university's fertility clinic, which included measurement of their reproductive hormones and metabolic parameters.

The researchers found a 12-fold increased risk of hypogonadism, or low testosterone levels, in men with low sperm counts. Half the men with low testosterone had osteoporosis or low bone mass, a possible precursor to osteoporosis, as found on a bone density scan.

These study findings, according to Ferlin, suggest that low sperm count of itself is associated with poorer measures of cardiometabolic health but that hypogonadism is mainly involved in this association. He cautioned that their study does not prove that low sperm counts cause metabolic derangements, but rather that sperm quality is a mirror of the general male health.

The bottom line, Ferlin stressed, is that treatment of male infertility should not focus only on having a child when diagnostic testing finds other health risks, such as overweight, high cholesterol or high blood pressure.

"Men of couples having difficulties achieving pregnancy should be correctly diagnosed and followed up by their fertility specialists and primary care doctor because they could have an increased chance of morbidity and mortality," he said.

Credit: 
The Endocrine Society

Mediterranean diet is linked to higher muscle mass, bone density after menopause

CHICAGO--The heart-healthy Mediterranean diet also appears to be good for an older woman's bones and muscles, a new study of postmenopausal women in Brazil finds. The study results will be presented Monday at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

The researchers reported finding higher bone mass and muscle mass in postmenopausal women who adhered to a Mediterranean diet than in those who did not. This way of eating involves a high intake of fruits and vegetables, grains, potatoes, olive oil and seeds; moderately high fish intake; low saturated fat, dairy and red meat consumption; and regular but moderate drinking of red wine. The Mediterranean diet has been linked to a lower risk of heart disease, diabetes, cancer and certain other chronic diseases.

Few studies, however, are available about the Mediterranean diet and its effects on body composition after menopause, said the study's lead investigator, Thais Rasia Silva, Ph.D., a postdoctoral student at Universidade Federal do Rio Grande do Sul in Brazil. This information is important, she said, because menopause, with its decline in estrogen, speeds a woman's loss of bone mass, increasing her risk of the bone-thinning disease osteoporosis and broken bones. In addition, menopause and aging reduce muscle mass. Silva said declines in skeletal muscle mass and strength in older people are major contributors to increased illness, reduced quality of life and higher death rates.

Silva and her co-workers conducted their study in 103 healthy women from southern Brazil, who had an average age of 55 and who had gone through menopause 5.5 years earlier, on average. All women underwent bone scans to measure their bone mineral density, total body fat and appendicular lean mass, which was used to estimate skeletal muscle mass. The subjects also completed a food questionnaire about what they ate in the past month.

A higher Mediterranean diet score (MDS), meaning better adherence to the Mediterranean diet, was significantly associated with higher bone mineral density measured at the lumbar spine and with greater muscle mass, Silva reported. This association, she said, was independent of whether the women used hormone therapy previously, their prior smoking behavior or their current level of physical activity, as measured by wearing a pedometer for six days.

"We found that the Mediterranean diet could be a useful nonmedical strategy for the prevention of osteoporosis and fractures in postmenopausal women," Silva said.

Given the many health benefits of the Mediterranean diet, Silva added, "Postmenopausal women, especially those with low bone mass, should ask their doctor whether they might benefit from consuming this dietary pattern."

Credit: 
The Endocrine Society

High-energy breakfast promotes weight loss

CHICAGO--In patients with obesity and type 2 diabetes, a meal schedule that includes a high-energy breakfast promotes weight loss, improves diabetes and decreases the need for insulin, new research from Israel reports. The study results will be presented Saturday, March 17, at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

"This study shows that, in obese insulin-treated type 2 diabetes patients, a diet with three meals per day, consisting of a big breakfast, average lunch and small dinner, had many rapid and positive effects compared to the traditional diet with six small meals evenly distributed throughout the day: better weight loss, less hunger and better diabetes control while using less insulin," said lead study author Daniela Jakubowicz, M.D., professor of medicine at Tel Aviv University.

"The hour of the day--when you eat and how frequently you eat--is more important than what you eat and how many calories you eat," she noted. "Our body metabolism changes throughout the day. A slice of bread consumed at breakfast leads to a lower glucose response and is less fattening than an identical slice of bread consumed in the evening."

Jakubowicz and her colleagues studied 11 women and 18 men who had obesity and type 2 diabetes, being treated with insulin and averaged 69 years of age. The patients were randomly assigned to consume one of two different weight-loss diets, which contained an equal number of daily calories, for three months. One group (Bdiet) ate three meals: a large breakfast, a medium-sized lunch and a small dinner. The second group (6Mdiet) ate the traditional diet for diabetes and weight loss: six small meals evenly spaced throughout the day, including three snacks.

Overall glucose levels and glucose spikes were measured for 14 days at baseline, during the first two weeks on diet, and at the end of the study by continuous glucose monitoring (CGM). Glucose levels were tested every two weeks and insulin dosage was adjusted as needed.

At three months, while the Bdiet group lost 5 kilograms (11 pounds) the 6Mdiet group gained 1.4 kg (3 lb).

Fasting glucose levels decreased 54 mg/dl (from 161 to 107) in the Bdiet group but only 23 mg/dl (from 164 to 141) in the 6Mdiet group. Overall mean glucose levels dropped in the first 14 days by 29 mg/dl (from 167 to 138 mg/dl) and 38 mg/dl (from 167 to 129 mg/dl) after three months in the Bdiet group. Overall mean glucose levels dropped only 9 mg/dl (from 171 to 162 mg/dl) in the first 14 days and only 17 mg/dl (from 171 to 154 mg/dl) in the 6Mdiet group.

Mean glucose levels during sleep dropped only in the Bdiet group, by 24 mg/dl (from 131 to 107), but not in the 6Mdiet group.

The Bdiet group needed significantly less insulin (-20.5 units/day, from 54.7 to 34.8) while the 6Mdiet group needed more insulin (+2.2 units/day, from 67.8 to 70).

Carbohydrate craving and hunger decreased significantly in Bdiet group but increased in the 6Mdiet group.

Importantly, the researchers found a significant reduction of overall glycemia after as little as 14 days on Bdiet, when the participant had almost the same weight as at baseline. This finding suggests that even before weight loss, the change in the meal timing itself has a quick beneficial effect on glucose balance that is further improved by the important weight loss found in the 3M diet.

"A diet with adequate meal timing and frequency has a pivotal role in glucose control and weight loss," Jakubowicz observed.

The Ministry of Health of Israel supported the study.

The researchers will discuss their findings during a press conference at 10 a.m. Central on Sunday, March 18. Register to view the live webcast at endowebcasting.com.

Credit: 
The Endocrine Society

Dimethandrolone undecanoate shows promise as a male birth control pill

CHICAGO--A new birth control pill for men appears to be safe when used daily for a month, with hormone responses consistent with effective contraception, study researchers say. Their study results, in 83 men, will be presented Sunday at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill.

Like the pill for women, the experimental male oral contraceptive--called dimethandrolone undecanoate, or DMAU--combines activity of an androgen (male hormone) like testosterone, and a progestin, and is taken once a day, said the study's senior investigator, Stephanie Page, M.D., PhD, professor of medicine at the University of Washington, Seattle, Wash.

"DMAU is a major step forward in the development of a once-daily 'male pill'," Page said. "Many men say they would prefer a daily pill as a reversible contraceptive, rather than long-acting injections or topical gels, which are also in development."

Progress toward a male birth control pill has been stymied because, according to Page, available oral forms of testosterone may cause liver inflammation, and they clear the body too quickly for once-daily dosing, thus requiring two doses a day. However, DMAU contains undecanoate, a long-chain fatty acid, which Page said slows this clearance. DMAU is being developed by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, which funded this study.

The study included 100 healthy men, ages 18 to 50 years, and took place at the University of Washington Medical Center and at Harbor-UCLA Medical Center in Torrance, CA (led by co-author Christina Wang, M.D.). The investigators tested three different doses of DMAU (100, 200, and 400 milligrams, or mg) and two different formulations inside the capsules (castor oil and powder). Each dose group included five subjects who were randomly assigned to receive an inactive placebo and another 12 to 15 men who received DMAU. Subjects took the drug or placebo for 28 days once daily with food. DMAU must be taken with food to be effective, Page noted.

A total of 83 men completed the study, including giving blood samples, for hormone and cholesterol testing, on the first and last days of the study.

At the highest dose of DMAU tested, 400 mg, subjects showed "marked suppression" of levels of their testosterone and two hormones required for sperm production. The low levels, Page said, are consistent with effective male contraception shown in longer-term studies.

"Despite having low levels of circulating testosterone, very few subjects reported symptoms consistent with testosterone deficiency or excess," Page said.

All groups taking DMAU did have weight gain and decreases in HDL ("good") cholesterol, both of which Page said were mild. All subjects passed safety tests, including markers of liver and kidney function.

"These promising results are unprecedented in the development of a prototype male pill," Page said. "Longer term studies are currently under way to confirm that DMAU taken every day blocks sperm production."

Credit: 
The Endocrine Society

The Swiss army knife of smoke screens

image: A new type of smoke grenade that can obscure sensors in the visible and infrared ranges burns during a test.

Image: 
US Army

NEW ORLEANS, March 18, 2018 -- Setting off smoke bombs is more than good fun on the Fourth of July. The military uses smoke grenades in dangerous situations to provide cover for people and tanks on the move. But the smoke arms race is on. Increasingly, sensors can now go beyond the visible range into the infrared (IR) region of the spectrum. Today, researchers report developing a new kind of smoke that obscures both visible and IR detection.

The researchers will present their work today at the 255th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 13,000 presentations on a wide range of science topics.

"Because of the advancement of sensors beyond the visible region, we need new, high-performing obscurants in the infrared region," Zach Zander says. "Each obscurant can absorb or scatter light at a given frequency. Most of the smokes that we use do well in either the visible or IR range. The objective of this program is to create what we call a bispectral obscurant, which works to block visible, as well as infrared detection."

To build a better puff of smoke, Zander and his colleagues in the Smoke & Obscurants, Pyrotechnics, and Chemical Biological Filtration Branches started thinking about using a metal organic framework (MOF). Other scientists working at his institute, the U.S. Army's Edgewood Chemical Biological Center, have been studying these stable porous structures, and were working with one called UiO-66 that was made up of terephthalic acid, a known visible obscurant.

"The traditional army smoke grenade is made with a toxic material, called hexachloroethane, but terephthalic acid grenades are emerging as a safer alternative," says Zander. The rest of UiO-66 consists of large pores and a zirconium node that researchers proposed could absorb in the IR range. The question was whether UiO-66 would burn in such a way as to liberate the terephthalic acid from the framework, creating a smoke with both an IR-absorbing agent and a visible light obscurant. If the UiO-66 molecule didn't break apart, the terephthalic acid wouldn't be free to block the visible light.

In a proof-of-principle experiment, the researchers packed UiO-66 into a grenade along with the pyrotechnic agents that generate the burn. They placed it in a 249-cubic-yard chamber lined with sensors and set off the smoke grenade.

"We monitored visible and IR wavelengths," Zander says. "We got some blockage in the visible range, though it wasn't as good as a true terephthalic acid grenade. We think we can improve our performance by changing the recipe of the pyrotechnic portion and thereby better liberate the terephthalic acid from the framework."

In the long term, the researchers plan to continue incorporating additional obscurants to the smoke, creating a kind of "Swiss army knife" of smoke grenades. "Ideally, we'd like one smoke device that hits multiple spectra, rather than multiple devices to hit each spectrum individually," Zander says. "The reason this is so important to the army is that you want to minimize the amount of stuff a soldier has to carry. One grenade is definitely easier to haul than five."

Credit: 
American Chemical Society

Living sensor can potentially prevent environmental disasters from fuel spills

NEW ORLEANS, March 18, 2018 -- The Colonial Pipeline, which carries fuel from Texas to New York, ruptured last fall, dumping a quarter-million gallons of gas in rural Alabama. By the time the leak was detected during routine inspection, vapors from released gasoline were so strong they prevented pipeline repair for days. Now, scientists are developing technology that would alert pipeline managers about leaks as soon as failure begins, avoiding the environmental disasters and fuel distribution disruptions resulting from pipeline leaks.

The researchers are presenting their work today at the 255th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 13,000 presentations on a wide range of science topics.

"The advantage with our sensor is that it can detect very small leaks, and operators can take quick action to repair them," says Veera Gnaneswar Gude, Ph.D., leader of the project. "We no longer have to wait until the leak is out of hand. Plus if we are able to develop this system on a larger scale, the same unit would be able to treat the waste and to remediate the soil and water that has been contaminated."

Pipelines are currently inspected by a device called a smart pig, an electronic sensor that travels through the pipe detecting cracks or welding defects. Despite regular inspection, leaks still occur. Gude, who is at Mississippi State University, is developing a sensor that would complement this process by providing additional information about the integrity of the pipes. This sensor adheres to the outside of the pipe, and takes advantage of the metabolic process of bacteria to detect gas leaks in real time.

In previous research, Gude studied the use of microorganisms in wastewater treatment, and he has recently turned his focus to building biosensors from similar species. In the current study, he is testing bacteria that will elicit an adequately measurable cathode voltage while also being able to survive in a marine environment for the application of offshore oil spill detection. For this to work, the bacteria have to remain robust through a range of alkalinity, pressure and pH conditions.

One type of bacteria he is testing is referred to as "electrogenic," which means that it releases electrons to its environment through metabolic processes. Gude created an organic sensor composed of an electrogenic anode made up of bacteria that consume carbon-based material (gas or oil) and expel electrons. The electrons then travel across a resistor to a cathode. A different set of bacteria, hungry for electrons, resides at the cathode encouraging electron flow. An increase in the metabolic processes of the anode bacteria will correspond to a voltage increase in the sensor, which could alert a technician to a potential leak.

"The sensor is not difficult to implement," says Gude. "Placing the sensor onto a pipe is not a big challenge. It is a very versatile technique."

Currently, Gude is looking for a medium in which to immobilize the bacteria. He is testing high-porosity plastics and bio-based films that optimize the surface area that the electrogenic bacteria can cover.

Once rugged bacteria are identified and immobilized, they can be used as leak detectors in a range of oil transport and drilling applications, including fracking. It is possible that at some point in the future the sensor could be sprayed as a coating on the exterior of pipes insuring that the entire length is continuously monitored.

Credit: 
American Chemical Society

Prenatal exposure to plasticizer may affect male fertility in future generations

CHICAGO -- Chemicals found in a variety of routinely used consumer products may be contributing to the substantial drop in sperm counts and sperm quality among men in recent decades, a new study in mice suggests.

The study found the effect of chemicals that disrupt the body's hormones, called endocrine-disrupting chemicals, may extend beyond more than one generation. The research results will be presented Monday, March 19, at ENDO 2018, the 100th annual meeting of the Endocrine Society, in Chicago, Ill.

"Sperm counts among men have dropped substantially over the last few decades, but the reason for such an alarming phenomenon is not known. These results suggest that when a mother is exposed to an endocrine disruptor during pregnancy, her son and the son's future generations may suffer from decreased fertility or hormone insufficiency," said lead author Radwa Barakat, B.V.S.C., M.Sc., of the College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Ill.

The researchers studied the effect of di-(2-ethylhexyl) phthalate (DEHP), which is among the most widely used endocrine-disrupting chemicals. It is found in a wide array of industrial and consumer products, including polyvinyl chloride (PVC) piping and tubing, cosmetics, medical devices and plastic toys. The study found that male mice exposed to DEHP prenatally had significantly less testosterone in their blood and fewer sperm in their semen. Consequently, they lost fertility at an age when they normally would have been fertile.

"Most surprisingly, the male mice born to male mice that were exposed to DEHP also exhibited similar reproductive abnormalities--indicating prenatal exposure to DEHP can affect the fertility and reproductive capacity of more than one generation of offspring," Barakat said. "Therefore, DEHP may be a contributing factor to the decreased sperm counts and qualities in modern men compared to previous generations."

Barakat and colleagues gave pregnant mice one of four doses of DEHP, or a type of corn oil, from 11 days after they conceived until birth.

Adult males born to these mice were bred with unexposed female mice, to produce a second generation of mice. Young adult males from this second generation were bred with unexposed females to produce a third generation. When each generation of mice was 15 months old, the researchers measured sex hormone levels, sperm concentrations and sperm motility, or movement (a potential sign of infertility).

In second-generation males, only those descended from mice in the highest DEHP exposure group had abnormal reproductive results--lower testosterone concentration, sperms levels and sperm motility. Third-generation males descended from DEHP-exposed mice also exhibited reproductive abnormalities at age 15 months, even those descended from mice that received a lower dose of the chemical. The researchers were surprised to find that the lowest DEHP dose group exhibited the greatest abnormalities.

"This study underscores the importance of educating public to try their best effort to reduce their exposure to this chemical and also the need to substitute this chemical with a safer one," Barakat said.

Credit: 
The Endocrine Society

Clinical medicine training prepares medical students to treat transgender patients

CHICAGO--Medical students who are specifically trained in clinical transgender medicine are better prepared to treat transgender patients, a new study from Boston University School of Medicine suggests. The study results will be presented in a poster Saturday, March 17 at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

"The number one barrier to quality transgender medical care is the lack of trained clinicians," study co-authors Jason Andrew Park, a medical student, and Joshua David Safer, M.D., the medical director of the Center for Transgender Medicine and Surgery, said in a joint statement.

"Boston University School of Medicine introduced a clinical elective where students can participate in direct medical care for transgender patients. The students who participated in the elective reported greater confidence in providing care to transgender individuals than the same students had reported from classroom instruction alone," they noted.

To augment the school's mandatory training of medical students in gender identity and transgender medicine, the authors implemented a pilot Transgender Medicine elective that enabled fourth-year medical students to rotate on services that provided direct transgender-specific clinical care for transgender patients. The 20 students in the program had already taken part in an elective in which they learned methods of providing transgender medical care.

In a survey at the beginning of the pilot elective, all the students expressed the opinion that medical schools and residency programs need to provide training in transgender health. In a survey after completing the elective, the students reported significantly improved confidence in their ability to provide care to transgender patients. Students rating their comfort as "high" increased from 45 percent (9 students) at baseline to 80 percent (16 students), and those rating their knowledge of the management of transgender patients as "high" rose from zero to 85 percent (17 students).

The percentage of students rating their skills for providing general care to transgender patients as "low" decreased from 35 percent (7 students) at baseline to zero, and the number rating their skills for providing hormone treatment to transgender patients as "low" dropped from 10 students to 1.

"Transgender individuals are medically underserved in the United States and face many documented disparities in care due to providers' lack of education, training, and comfort. Clinical exposure to transgender medicine during clinical years can contribute to closing the gap between transgender and LGB care and to improving access to care," the authors wrote in their abstract.

Credit: 
The Endocrine Society

Not having a regular doctor affects healthcare quality for older adults

March 16, 2018 - About five percent of older adults on Medicare don't have a "personal physician," and this group scores lower on measures of healthcare quality, reports a study in the April issue of Medical Care, published by Wolters Kluwer.

"Beneficiaries without personal physician report worse care experiences, rating their overall quality of care substantially lower than those with a personal physician," according to the new research by Marc N. Elliott, PhD, of The RAND Corporation, Santa Monica, Calif., and colleagues. They believe that encouraging Medicare recipients to have a regular doctor might help to improve continuity and quality of healthcare.

Some Groups of Medicare Patients Less Likely to Have a Personal Physician

The researchers analyzed data from more than 272,000 elderly Medicare beneficiaries responding to a nationally representative survey (the 2012 Consumer Assessment of Healthcare Providers and Systems survey). The survey included a question about whether the respondents had a personal physician: a doctor they would see for a checkup, if they wanted advice about a health problem, or if they got sick or hurt.

Overall, 4.9 percent of Medicare recipients said they did not have a personal physician. While that rate seems low, Dr. Elliott and coauthors note that five percent of the Medicare population amounts to more than two million people.

The rate was even higher for certain groups, including men, racial/ethnic minorities, and those with lower education. The percentage without a regular doctor rose to 9.3 percent for respondents with less than a high-school education, 10.5 percent for Hispanic beneficiaries, and 16.3 percent for American Indians/Alaska Natives.

Beneficiaries without a personal physician were more likely to be enrolled in fee-for-service Medicare without a prescription drug plan, and less likely to be enrolled in Medicare Advantage plans. While older adults without a regular doctor had better overall health, they had poorer mental health.

Not having a regular doctor was associated with lower scores on measures of patient care experience, including an eight-point reduction (out of 100 points) in rating of overall healthcare. Respondents without a personal physician also scored lower on measures of getting needed care, getting care quickly, and getting needed drugs.

The effects on care were larger than those associated with key demographic characteristics, include ethnicity, socioeconomic status, sex, and age. "Beneficiaries without a personal physician were more than three times as likely to have not seen any healthcare provider in the last six months," the researchers add.

Having a personal physician is an important aspect of continuity of care, which is linked to improvement in a wide range of healthcare quality measures. But little is known about which groups are less likely to have a personal physician, or if care experience differs for patients with or without a regular doctor. The health benefits associated with continuity of care may be especially important for older adults on Medicare.

The study confirms previous research reporting racial/ethnic disparities in having a usual source of healthcare or a personal physician. It also identifies other characteristics associated with not having a regular provider, including male sex and lower education. The authors note some limitations of their study, including a lack of data on other factors that likely affect patient experience.

"Our findings provide further evidence of the relatively poorer care experiences among those who do not have a personal physician," Dr. Elliott and colleagues conclude. "Medicare would be well-served to better understand who does and does not have a personal physician and take actions to help connect beneficiaries to providers."

Credit: 
Wolters Kluwer Health

Human 'chimeric' cells restore crucial protein in Duchenne muscular dystrophy

Cells made by fusing a normal human muscle cell with a muscle cell from a person with Duchenne muscular dystrophy --a rare but fatal form of muscular dystrophy -- were able to significantly improve muscle function when implanted into the muscles of a mouse model of the disease. The findings are reported by researchers from the University of Illinois at Chicago in the Stem Cell Review and Reports.

These cells, called "chimeric cells," are made by combining a normal donor cell containing a functioning copy of the gene for dystrophin -- a structural muscle protein lacking in people with Duchenne muscular dystrophy -- with a cell from a recipient with the disease. In a January 2018 paper in Stem Cell Reviews and Reports, the researchers used mouse donor and recipient cells to make chimeric cells that boosted dystrophin levels by 37 percent and improved muscle function when implanted into the muscles of a mouse model of Duchenne muscular dystrophy. The new cells had both donor and recipient characteristics and interacted with their surroundings like normal cells. The chimeric cells remained viable and produced dystrophin for 30 days.

Now, the research group, led by Dr. Maria Siemionow, professor of orthopedic surgery in the UIC College of Medicine, report similar findings using human cells implanted in a mouse model of Duchenne muscular dystrophy.

"Our results point to the long-term survival of these cells and helps establish the use of chimeric cells as a novel promising potential therapy for patients with Duchenne muscular dystrophy," Siemionow said. Her team is looking forward to clinical trials in humans in the near future, she said.

Duchenne muscular dystrophy is an X-linked genetic disorder characterized by progressive muscle degeneration and weakness, affecting approximately 1 in 4,000 newborn boys.

People with the disease don't have the gene for dystrophin, a structural protein that helps keep muscle cells intact. Symptom onset is in early childhood, usually between ages 3 and 5. The disorder causes muscle weakness and loss of motor function and ultimately results in respiratory or cardiac failure and death. With advances in treatment, many with Duchenne muscular dystrophy live into their teens and 20s, and some into their 30s, but there is currently no cure for the disease.

Promising treatments include gene therapy and stem cell therapy, but each has drawbacks. Gene therapy relies on delivering good copies of missing or dysfunctional genes to cells via viruses. Not only can cells become immune to viral infection, rendering the therapy ineffective, but there also is no guarantee that viruses will only infect the intended cells. Stem cell therapy, where cells that contain the dystrophin gene are implanted into a recipient, requires that the recipient take immunosuppressive drugs to prevent rejection.

"This is not conventional stem cell therapy," said Siemionow, who is the lead author of the paper. "We are restoring dystrophin in such a way that the recipient won't need to take anti-rejection therapy because the implanted chimeric cells can evade the recipient's immune system. In traditional stem cell therapy, the implanted cells are 100 percent 'other' and anti-rejection medicine is needed in order to prevent the host immune system from destroying those foreign cells."

In contrast, chimeric cells are 50 percent "self" -- with many biochemical and genetic features of the recipient -- and as such can trick the recipient's immune system into ignoring them.

"The chimeric cells are just enough like the recipient's own cells that their immune system gives them a 'pass' so to speak," Siemionow said.

If such cells were to be used to treat a patient with Duchenne muscular dystrophy, then normal muscle cells from the recipient's father or close relative would be fused with muscle cells from the patient.

The researchers fused muscle cells from patients with Duchenne muscular dystrophy with muscle cells from normal, healthy donors.

In the lab, the chimeric cells were seen to express dystrophin.

When the cells were implanted into the leg muscles of a mouse model of Duchenne muscular dystrophy, dystrophin levels rose approximately 20 percent of muscle fibers affected by the implanted cells at 90 days post-implantation, "enough to produce a significant improvement in muscle function," said Dr. Kris Siemionow, associate professor of orthopedic surgery in the UIC College of Medicine and a co-author on the paper.

Improvements of more than 60 percent were seen in muscle function tests of the implanted mice, and improvements of more than 20 percent in tests of muscle fatigue tolerance.

Maria and Kris Siemionow, who are mother and son, have recently launched a company to develop their chimeric cells into a therapy to treat Duchenne muscular dystrophy called Dystrogen Therapeutics.

Credit: 
University of Illinois Chicago

First accurate data showing male to female transgender surgery can give better life

Scientists have developed a transgender-specific questionnaire, which confirms for the first time that gender surgery significantly improves quality of life for the majority of patients. The study shows that 80% of male-to-female patients perceived themselves as women post-surgery. However, the quality of life of transgender individuals is still significantly lower than the general population.

Many transgender individuals request gender reassignment surgery, but until now there only existed information on general aspects of health related quality of life (QoL) and non-validated questionnaires about improvement of QoL. A team at the University hospital in Essen, Germany, led by Dr. Jochen Hess, followed 156 patients for a median of more than 6 years after surgery. They developed and validated the new Essen Transgender Quality of Life Inventory, which is the first methodology to specifically consider transgender QoL.

They found that there was a high overall level of satisfaction with the outcomes of surgery. When comparing the QoL of the last four weeks with the QoL during the time of publicly identifying as transgendered there was a highly significant increase on all subscales of the ETL as well as for the global score indicating a large improvement of QoL in the course of the transitioning process.

Doctor Hess commented

"The good news is that we found that around three-quarters of patients showed a better quality of life after surgery. 80% perceived themselves to be women, and another 16% felt that they were 'rather female'. 3 women in 4 were able to have orgasms after reassignment surgery.

It's very important that we have good data on Quality of Life in transgender people. They generally suffer from a worse QoL than non-transgender population, with higher rates of stress and mental illness, so it's good that surgery can change this, but also that we can now show that it has a positive effect. Until now we have been using general methods to understand quality of life in transgender individuals, but this new method means that we can address well-being in greater depth".

Recent data1 estimates that 1.4 million adults in the USA identify as transgender, which is about 0.6% of the population. Comparable European figures are not available, but there is wide variation between reported prevalence in individual European countries. Transgender individuals have seen greater visibility in recent years due to the openness of personalities such as Caitlin Jenner, Chelsea Manning, and Andreja Pejic.

The team notes that there are limitations to the study: there was a high drop-out rate, and the results are from a single centre (NOTE: please see information in 'Notes for Editors', which contains more information on the drop-out rate. Info also available directly from press officer).

"Nevertheless, we now have the first specific validated tool for measuring QoL in transgender patients, we hope that this means that we can go forward to gather better information to help us improve treatment", said Dr. Hess.

Commenting, Prof Professor Piet Hoebeke (Ghent University Hospital, Belgium) said:

"As patients develop a better understanding and higher acceptance of transgender surgery, more will seek gender confirming surgery. Despite this observation many doctors are still not convinced that this is a medical condition for which surgery can be offered as a valuable treatment. We need studies like this one to convince the medical world that these patients can get a better QOL with treatment".

Professor Jens Sønksen (University of Copenhagen) commented

"This study suffered from a high drop-out rate, which needs to be considered alongside the main data. Nevertheless, this is a large important study, one of the largest clinical transsexual surveys ever attempted, and the fact that has been performed using a specific validated questionnaire is significant. This is probably the best view of quality of life in after sex-reassignment that we have".

Neither Professor Hoebeke nor Professor Sønksen were involved in this work, these are independent comments.

Credit: 
European Association of Urology

Online intervention improves depression treatment rates in teen moms

image: This is M. Cynthia Logsdon, Ph.D., W.H.N.P.-B.C., F.A.A.N.

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University of Louisville

LOUISVILLE, Ky. - An online program persuaded teenage mothers across 10 Kentucky counties to seek medical help for depression, highlighting an inexpensive way to increase mental health treatment rates for the vulnerable group, according to a University of Louisville study.

The website included videos of adolescent mothers describing their experiences with postpartum depression and treatment, questions and answers, and local and national resources, including referrals for counseling services and suicide and child-abuse prevention hotlines.

Untreated postpartum depression hinders a mother's relationship with her child, her functioning at work and school, mothering skills and development. The condition also can harm a baby's development and attachment to the mother, said M. Cynthia Logsdon, Ph.D., W.H.N.P.-B.C., UofL School of Nursing professor and lead researcher of the study.

Half of the roughly 400,000 adolescents 18 and younger who give birth annually in the United States experience depressive symptoms, but less than 25 percent follow referrals for depression evaluation and treatment, according to the study.

The research, conducted from 2013 to 2016, involved more than 200 teen moms in urban, suburban and rural counties in Kentucky and was funded by a nearly $440,000 grant from the National Institutes of Health.

Study participants on average were 18 years old, primarily African-American, did not have a high school diploma and had given birth in the past year.

For both rural and urban counties, the intervention led to significant changes in attitude, intention to seek depression treatment and actually seeking treatment.

Credit: 
University of Louisville

80% cut in liver metastasis by restricting the blood vessels supplying it

image: The researchers from left to right: Joana Márquez, Fernando Unda, Iker Badiola abd Gaskon Ibarretxe.

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(UPV/EHU)

Metastasis is the process whereby a tumour that grows in one organ breaks away from it and travels to another organ and colonises it. In the colonisation process it needs to create new blood vessels through which the cancer cells obtain the nutrients and oxygen they need to grow. This blood vessel formation process is called angiogenesis and is carried out by the endothelial cells. "Unlike normal endothelial cells and due to the signals that reach them from the tumour cells, the cells that supply the tumours have increased growth and tend to move towards the metastatic mass to help it grow," said Iker Badiola, member of the Signaling Lab research group in the Department of Cell Biology and Histology of the UPV/EHU's Faculty of Medicine and Pharmacy.

In order to find out what is actually causing this change in the endothelial cells, the UPV/EHU's Signaling Lab Research Group and the Department of Pharmacology, Pharmacy and Pharmaceutical Technology of the University of Santiago de Compostela, in collaboration with other groups of researchers, embarked on research using mice. The ultimate aim was, as Badiola pointed out, "to slow down the metastatic process by impacting on angiogenesis in the event of bringing about the restoration of the endothelial cells". In the research they induced liver metastasis in mice by using colon cancer cells and from the mass they extracted endothelial cells. They then compared these endothelial cells with other healthy ones. The comparison made covered two aspects: on a protein level, in which they saw which proteins appeared and which did not in each cell type, and to what degree they did so, and in the same way with respect to the degree of micro-RNA. Micro-RNA consists of small elements which for some time were not thought to perform any function but which are now known to play a role in protein regulation.

Using Biocomputing tools they screened and selected the proteins and relevant micro-RNA elements, and "in the final step in this selection process we ended up with a specific micro-RNA: miR-20a. This is an element that appears in healthy endothelial cells, but disappears in those that are in contact with the tumour. We saw that due to the disappearance of the miR-20a in the endothelial cells, a set of proteins appeared and that was when their behaviour began to change and they started to grow and move around," explained Badiola.

Restoring miR-20a using nanoparticles

They then started experiments to see whether including the miR-20a element would restore the behaviour of the endothelial cells that supply the tumours. To do this, they developed nanoparticles "designed to target the endothelial cells in the liver and loaded with miR-20a. We administered them to mice in which we had previously induced metastasis to find out the effect. The pathological analysis revealed that, in the cases treated, far fewer new blood vessels had formed inside the tumours. We also confirmed that the number and size of the metastatic masses had fallen by 80%", he said.

Badiola positively rates being able to reduce metastasis size by 80%, but he makes it clear that "if it is ever used as a treatment, it will be a complementary treatment. You can't ignore the fact that the metastasis goes on growing 20% and, what is more, at no time are the tumour cells destroyed nor are they attacked directly. The strategy of tackling the metastasis that we have achieved involves limiting the supply of nutrients and oxygen; in other words, we restrict the help".

Credit: 
University of the Basque Country