Body

Soft tissue sarcomas are a heterogenous group of aggressive, chemotherapy-resistant cancers that affect the soft tissues of the body (fat, muscles, fibrous tissue, blood and lymphatic vessels, nerves, etc.). In the current clinical trials, only 15% of patients respond to immunotherapy, which raises the question of the needless exposure of the other patients to the toxicity of these treatments. Identifying markers that predict their response to immunotherapy is therefore crucial. A strategy that until now has been essentially focused on the T cells - immune cells capable of recognizing cells that are infected, cancerous or foreign to the body.

Through research published in Nature, a group led by Wolf Hervé Fridman with members from Inserm, Sorbonne Université and Université de Paris at the Cordeliers Research Center, in collaboration with the "Tumor identity card" team from the French League against cancer, Institut Bergonié, and teams from the USA and Taiwan, studied the question of identifying other potential markers.

They analyzed 608 tumors, classifying them into three groups according to the composition of their microenvironment : immunologically poor tumors (low in immune cells and poorly vascularized), highly vascularized tumors, and immunologically rich tumors. The latter present aggregates of various cell types with high levels of B cells, the immune cells responsible for the production of antibodies. These aggregates are called tertiary lymphoid structures. The researchers observed that an anti-tumor immune response initiates within them, thereby showing that the B cells could play an anti-tumor role.

What is more, in a phase 2 clinical trial, the patients with immunologically rich tumors showed a high response rate (50%) to one immunotherapy: pembrolizumab. These patients also had a higher survival rate than those with immunologically poor or highly vascularized tumors.

A second study by a US team, co-signed by Wolf Hervé Fridman's team at Cordeliers Research Center (Inserm/Sorbonne Université/Université de Paris), and published in parallel in Nature, extended these observations to include melanoma and kidney cancer.

The results of these studies show that in addition to the T cells that are usually researched, the B cells play an essential role in the response to immunotherapy for certain cancers. These cells bring new hope for the treatment of soft tissue sarcomas, which are particularly resistant to standard therapies. In addition, from a personalized medicine standpoint, these findings could help orient clinical decisions and patient treatment by means of a simple test to identify those whose tumors are immunologically rich.

On the basis of these results, an initial French clinical trial coordinated by Antoine Italiano (Institut Bergonié, Université de Bordeaux), co-author of the first article, and which includes patients with such tumors, is currently ongoing within the French Sarcoma Group.

A lengthy-named gene called Elongation of Very Long Chain Fatty Acids Protein 2 or ELOVL2 is an established biomarker of age. In a new paper, published online January 14, 2020 in the journal Aging Cell, researchers at University of California San Diego School of Medicine say the gene appears to play a key role in age-associated functional and anatomical aging in vivo in mouse retinas, a finding that has direct relevance to age-related eye diseases.

Specifically, the research team, led by senior author Dorota Skowronska-Krawczyk, PhD, assistant professor in the Viterbi Family Department of Ophthalmology at UC San Diego Shiley Eye Institute, found that an age-related decrease in ELOVL2 gene expression was associated with increased DNA methylation of its promoter. Methylation is a simple biochemical process in which groups of carbon and hydrogen atoms are transferred from one substance to another. In the case of DNA, methylation of regulatory regions negatively impacts expression of the gene.

When researchers reversed hypermethylation in vivo, they boosted ELOVL2 expression and rescued age-related decline in visual function in mice. "These findings indicate that ELOVL2 actively regulates aging in mouse retina, provides a molecular link between polyunsaturated fatty acids elongation and visual functions, and suggests novel therapeutic strategies for treatment of age-related eye diseases," wrote the authors.

ELOVL2 is involved in production of long-chain omega-3 and omega-6 polyunsaturated fatty acids, which are used in several crucial biological functions, such as energy production, inflammation response and maintenance of cell membrane integrity. The gene is found in humans as well as mice.

In particular, ELOVL2 regulates levels of docosahexaenoic acid or DHA, a polyunsaturated omega-3 fatty acid abundantly found in the brain and retina. DHA is associated with a number of beneficial effects. Notably, its presence in photoreceptors in eyes promotes healthy retinal function, protects against damage from bright light or oxidative stress and has been linked to improving a variety of vision conditions, from age-related macular (AMD) degeneration to diabetic eye disease and dry eyes.

Skowronska-Krawczyk said the work demonstrated for the first time that a "methylation clock" gene had a functional role in the aging of an organ. In this case, the eye. DNA methylation is used throughout the human body, essentially turning biological switches on an off to maximize efficient operation. It has key regulatory roles in the body's cardiovascular, neurological, reproductive and detoxification systems.

In recent years, there has been much work and progress in identifying possible biomarkers that predict the biological age (not chronological) of individuals. Such biomarkers would be useful in identifying risk and status of age-related diseases. ELOVL2 is among the genes attracting greatest interest.

"I have been asked whether I think ELOVL2 is the aging gene," said Skowronska-Krawczyk. "After thinking about it, it is not unreasonable to think that lower ELOVL2 expression might be at the basis for many age-related conditions. Future work in our lab will address that question."

Co-authors of this study include: co-first authors Daniel Chen and Daniel Chao as well as Lorena Rocha, Viet Ahn Nguyen Huu, Michal Krawczyk, Manish Dasyani, Tina Wang, Maryam Jafari, Mary Jabari, Kevin D. Ross, Bruce Hamilton, and Kang Zhang, all at UC San Diego; and Matthew Kolar and Alan Saghatelian, Salk Institute for Biological Studies.

A Brazilian study published in the journal Drug and Alcohol Dependence shows that cannabis smoked recreationally does not work as a harm reduction strategy for crack and cocaine addicts undergoing rehabilitation. Instead of reducing their craving for cocaine, whether nasally insufflated in powder form or smoked in the form of crack crystals, cannabis use made the patients' clinical condition worse.

The patients were evaluated for six months after discharge from a voluntary inpatient treatment program at the Psychiatry Institute of Hospital das Clínicas (HC), the general hospital run by the University of São Paulo Medical School (FMUSP). Researchers in FMUSP's Interdisciplinary Group for the Study of Alcohol & Drugs (GREA) and Psychiatric Neuroimaging Laboratory (LIM-21) found that cannabis use impaired central nervous system executive functions relating to impulse control, among others.

"The aim of the study was to ensure that public policy for drug users is based on scientific evidence. When damage limitation was introduced as a policy in Brazil for cocaine and crack users, there was no proof that it would be beneficial. Our study completely rules out this strategy for cocaine addicts," said Paulo Jannuzzi Cunha, a coauthor of the article. Cunha teaches graduate students in psychiatry at FMUSP and is a researcher affiliated with LIM-21. Previously, he was awarded a postdoctoral scholarship by São Paulo Research Foundation - FAPESP.

According to Cunha, the LIM-21 research group advocates a short period of hospitalization while chemically dependent patients are undergoing detoxification. He stressed that rehabilitation should be voluntary and should not entail isolating patients from society since they are prone to relapses.

"We aim to help them build up the strength to face their real problems in the context of their day-to-day domestic lives. They learn strategies for ridding themselves of the temptation to use the drug again. Long periods of inpatient treatment are expensive and remove the patient from reality. There's no guarantee they won't relapse after leaving seclusion," he said.

Currently, there are no approved pharmacological treatments for cocaine dependence. The researchers recommend cognitive behavioral therapy (CBT), contingency management, and psychiatric medical treatment of comorbidities such as depression, anxiety disorders, and attention deficit hyperactivity disorder (ADHD).

In many cases, these mental disorders occur in parallel with chemical dependence and jeopardize adherence to treatment, preventing the patient's recovery. "Integrated evidence-based treatment tends to be effective in the medium to long run," Cunha said. "In addition to providing multidisciplinary care, we advise addicts to participate in support groups made up of former users."

Months of follow up

In the study, 123 volunteers were divided into three groups: 63 cocaine addicts who smoked cannabis recreationally, 24 cocaine addicts who did not use cannabis frequently, and a control group consisting of 36 healthy individuals without a history of drug use.

The groups were followed for six months after the end of the inpatient treatment. One month after discharge, 77% of the cocaine addicts who smoked cannabis had maintained abstinence without relapses, compared with 70% of those who did not use cannabis.

Three months after discharge, however, cannabis use as a harm reduction strategy was no longer working well. Fewer than half of the subjects who didn't smoked cannabis (44%) and only 35% of those who did had not relapsed into cocaine use; the proportions were 24% and 19%, respectively, after six months. The researchers concluded that the addicts who used cannabis eventually resumed cocaine use in the long run.

"The results refuted the hypothesis that recreational cannabis could prevent relapse and help cocaine addicts achieve abstinence. A quarter of the noncannabis smokers were able to control the impulse to use cocaine, and only a fifth of those who expected to benefit from the harm reduction strategy had no relapses. Prior cannabis use doesn't improve the long-term prognosis. In fact, the study suggests the opposite," said psychiatrist Hercílio Pereira de Oliveira Júnior, the first author of the article.

Executive functions impaired

According to the findings of the study, both groups of cocaine addicts undergoing rehabilitation displayed significant neurocognitive impairments compared with the control group in tasks that involved working memory, speed processing, inhibitory control, mental flexibility and decision making.

However, the group that smoked cannabis performed even worse in tests of executive functions associated with attention span in specific contexts, the ability to memorize, the planning of complex behavior, mental processing speed, and impulse control.

Cognitive tests and neuroimaging scans were performed throughout the study. Urine samples were analyzed to detect drug use.

"One of the limitations of our study was the impossibility of analyzing the type of cannabis used by the volunteers. It was the drug they used at home or in some other personal context," Cunha said.

Cannabis preparations can contain at least 80 different cannabinoids, two of which are particularly relevant: THC, which is associated with relaxation, dependency and neurological damage, and cannabidiol (CBD), which can modulate the effects of THC. "Our study didn't include a specific assessment of the possible effects of CBD, which may have therapeutic potential but accounts for a very small proportion of smoked cannabis and is much harder to extract in pure form from the cannabis plant," Cunha said.

Impact of early use on rehabilitation

Another result of the study was the finding that the earlier the onset of cannabis and cocaine use in the lives of addicts, the greater the likelihood of relapse during cocaine rehabilitation.

"Previous research showed that early onset of substance abuse impairs neurodevelopment and hinders the organization of important neural networks in the brain. Early exposure to cannabis therefore entails a worse prognosis with regard to not only cannabis but also other substances," Oliveira Júnior said.

"This variable is predictive and points to the negative impact of cannabis and cocaine on brain maturation, characterizing a worse prognosis for the addiction."

Damage limitation for heroin addicts

The use of substances such as methadone, an opioid, has been considered an effective harm reduction strategy as part of rehabilitation treatment for people addicted to heroin and other injectable drugs, achieving a measure of success in various countries since the 1990s.

Based on the results with heroin addicts, previous uncontrolled studies sustained that recreational use of cannabis could be an effective strategy to reduce the craving for cocaine and crack. "This even resulted in harm reduction organizations and public policies advocating the use of smoked cannabis as a strategy to reduce anxiety and the craving for cocaine. Our study contradicts the view that this type of strategy is effective," Oliveira Júnior said.

Cunha explained that the different outcomes of harm reduction for users of cocaine, crack and heroin are due to the differences between the drugs. "Heroin abstinence very quickly produces physiological and biological withdrawal symptoms," he said. "Without the help of an opioid, an abstinent addict soon begins to sweat profusely and feel nauseous. The symptoms may also include seizures and other serious physical problems."

A pharmacological harm reduction strategy that mitigates withdrawal symptoms and gives the patient a bridge to long-term abstinence is fully appropriate, he added.

"In contrast, cocaine withdrawal symptoms relate more to mood. Typically, they include irritability and depression," he said. "The physical effects observed in users of injectable drugs aren't at all typical of cocaine withdrawal. Hence the importance of behavioral strategies that help patients deal better with their emotions and remain abstinent. This is more effective in the long run."

New Haven, Conn. -- The Obamacare program intended to reduce the risk of patients being readmitted after hospitalizations for heart attacks, heart failure, and pneumonia has not caused an increase in mortality risk for patients in emergency departments or observational units, according to a new report.

Doctors from Yale and the University of Texas (UT) Southwestern Medical Center conducted the study, which appears Jan. 15 in The BMJ (British Medical Journal).

The program -- formally called the U.S. Hospital Readmissions Reduction Program -- penalizes hospitals with higher than average readmission rates, and has led to national efforts to reduce the number of patients being readmitted to hospitals. Critics have warned that the program might incentivize hospitals to send home some people who need to be admitted a second time, increasing their risk of dying.

The new study evaluated trends in patient mortality from the time of the readmission program's announcement through its implementation. The researchers found no evidence of an increase in death associated with the program. In particular, among those seen in the emergency department or admitted to an observation ward (and not subsequently re-hospitalized), there was no evidence of an increase in the death rate over time, the researchers said.

"This study adds to the evidence that the readmission policy is safe and is not increasing the risk of death by turning away people who need to be re-hospitalized," said Harlan Krumholz, M.D., cardiologist and director of the Yale Center for Outcomes Research and Evaluation (CORE), and senior author of the report.

The study revealed that there is a national trend toward increased risk of death in the post-discharge period for patients with heart failure, but that the increase began prior to the announcement of the Obamacare readmission policy.

"We do not yet know the mechanism for the increase in mortality," said lead author Rohan Khera, M.D., of UT Southwestern. "However, the trends in rising mortality are concurrent with a decrease in in-hospital mortality and an increase in discharges directly to hospice facilities."

Khera said nearly half of the heart patients who died after leaving the hospital were patients that hospitals had discharged directly to hospice.

"While far from definitive evidence, these observations do suggest that some of the increase in deaths may represent triage of dying patients from the hospital to the post-discharge period," Khera said.

Researchers at Johns Hopkins Kimmel Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins University School of Medicine have developed an integrated genomic approach that potentially could help physicians predict which patients with nonsmall cell lung cancer will respond to therapy with immune checkpoint inhibitors.

Immune checkpoint inhibitors are transforming the field of cancer therapeutics. However, these successes are limited by the lack of biomarkers that identify patients most likely to respond. Tumor mutational burden (TMB), which is a measure of the number of mutations carried by tumor cells, is considered an emerging biomarker of response, but TMB values are confounded by the tumor purity -- the amount of tumor versus normal cells -- of the sample analyzed.

The research team, led by Valsamo Anagnostou, M.D., Ph.D., assistant professor of oncology, developed a novel computational approach that more accurately computes TMB. The researchers also developed an integrated model of response that combined corrected TMB with nuanced genomic features and each patient's antigen presentation ability. A description of the patent pending work is published in the inaugural issue of the journal Nature Cancer.

The method also could be used to accurately estimate TMB and optimize prediction of response to immunotherapy among patients with lung cancer, colon cancer, melanoma and other solid tumors, says Anagnostou, the lead study author.

"Immunotherapy is an exciting treatment modality for many tumors, but what we don't truly know is who will respond to immunotherapy and why, and if there are specific molecular features that can help predict response," Anagnostou says.

Current biomarkers used to assess a patient's response to immunotherapy include a test to measure the amount of the protein PD-L1 on cancer cells and TMB. "There are more and more studies coming out that show TMB is actually not as predictive as we thought it would be," says Victor Velculescu, M.D., Ph.D., professor of oncology and the study's senior author. "Some tumors with a high TMB do not respond to immunotherapy, and some tumors with low TMB benefit from immunotherapy. There is an urgent need to develop integrated biomarkers that explain the nuances of the tumor-immune system crosstalk that can better inform us in terms of the clinical course of the patient."

Anagnostou and colleagues initially evaluated 3,788 tumor samples (from bladder, breast, colon, head and neck, kidney and nonsmall cell lung cancers and melanomas) from the National Cancer Institute's Cancer Genome Atlas database, and 1,661 tumor samples from a previously published cohort of immunotherapy-treated patients. They investigated the complexities of observed TMB estimates derived from whole exome sequencing (a technique that sequences the entire protein-coding region of genes in a genome) and targeted next-generation sequencing (a technique that sequences target regions of interest in a genome). They found a significant correlation between TMB and tumor purity -- the higher the tumor purity, the closer it is to the true TMB of the tumor, whereas the lower the tumor purity, the more likely the TMB estimate will be inaccurate. "Observed TMB is strongly affected by low tumor purity, and this simple concept is completely underestimated in the clinical setting," says Noushin Niknafs, Ph.D., postdoctoral fellow and co-first author of the study.

To overcome this limitation, the team developed a computational approach to estimate corrected TMB values for each tumor based on tumor purity. They simulated 20,000 tumors with various levels of TMB and sequencing coverage using information from the Cancer Genome Atlas and generated a correction factor for each simulated tumor based on its purity. "The correction factors can be summarized in a user-friendly look up table," says Anagnostou. "For example, if a tumor sample had a purity of 20% to 30%, a clinician could look at the table and see a coefficient to multiply the sample by to better achieve true TMB." The team also developed an approach to correct TMB derived from targeted sequence data, and in a reanalysis of 1,661 tumor samples treated with immune checkpoint inhibitors, the researchers found that using corrected TMB estimates improved prediction of overall survival.

Next, the team worked to understand additional molecular features that can play a role in patient response to immunotherapy. They performed whole exome sequencing for 104 lung tumors treated with immune checkpoint inhibitors. Through comprehensive analyses of sequence and structural alterations, they discovered more activating mutations in receptor tyrosine kinase (RTK) genes (receptors that are key regulators of cell processes including cell proliferation, survival and metabolism) among tumors that did not respond to immunotherapy in several cohorts of patients. In addition, they identified a predominance of smoking related mutations in patients that respond to therapy. Together, corrected TMB, RTK mutations, the mutation smoking signature and the number of germline variants of human leukocyte antigen (HLA) -- cell-surface proteins responsible for the presentation of foreign antigens -- provided the team with a much more accurate prediction of patient response to immunotherapy compared to TMB alone, even the corrected TMB.

The team is continuing studies of this model with more patients who have received immunotherapy and for whom they are generating tumor sequencing data.

"We expect this approach is going to be incorporated into clinical practice, and it can change the way providers make decisions about their patients," Anagnostou says. "For example, if a clinician can know with certainty that the tumor has a high tumor mutation burden, they may choose to give immunotherapy as stand-alone therapy, whereas if the tumor has a low tumor mutation burden, they may choose to give chemotherapy plus immunotherapy."

The world's most common vision problem myopia or short/near sightedness, which causes damage to the eye and even blindness, just got easier to assess.

Progressive research at Flinders University in Australia has identified a new method to measure how it affects the eye, a new article in PLOS ONE reveals.

The work was based on testing of 70 volunteers, with the Flinders ophthalmology and medical device research institute experts taking a novel approach with optical coherence tomography (OCT), a device already available in most optometric and all ophthalmic practices.

"Our work uses the OCT and finds irregularities at this scale that correlate with the size of the eye, and therefore the degree of myopia," says eye specialist Dr Stewart Lake, from Flinders University.

"This may help monitor, measure, and explore the effects of myopia and how it leads to vision loss," he says, adding further development could make the system suitable for use in regular clinical practice.

Prior research elsewhere with MRI scanning has demonstrated large scale irregularities in the eyeball in highly myopic eyes.

OCT can sample the shape of the eye on a much smaller scale than MRI. The OCT testing will be far cheaper, is more readily available and repeatable as a test, researchers say in the article.

Myopia (short or near-sightedness) is for many an inconvenience requiring glasses or contact lens to correct. However, globally it is an epidemic and a major cause of vision loss and sometimes blindness.

Myopia is defined practically by the strength of lens required to correct eyesight. It was already known myopia relates very strongly to the size/length of the eyeball.

Global estimates forecast up to 5 billion people will have myopia and 1 billion people could suffer with high myopia by 2050, placing a significant burden on health systems to manage and prevent myopia-related ocular complications and vision loss.

This seven-fold increase, between 2000 and 2050, would make myopia the leading cause of permanent blindness worldwide (source - Holden et al 'Global Myopia Trends 2000-2050').

High myopia increases the risk of pathological ocular changes such as cataract, glaucoma, retinal detachment and myopic macular degeneration - all of which cause irreversible vision loss

It is easy to obtain antibiotics without prescription in retail pharmacies in China, even though selling antibiotics without a prescription conflicts with regulations, a study published in the open access journal Antimicrobial Resistance & Infection Control suggests. More work needs to be done to ensure that antibiotics are obtainable by subscription only, according to researchers at Zhejiang University School of Medicine, Hangzhou, China.

At the G20 summit in China in 2016, a comprehensive plan to address antimicrobial resistance (AMR) was announced, which included making antibiotics prescription-only in pharmacies in all Chinese provinces by 2020. The authors investigated the degree of progress towards that goal and to quantify the proportion of pharmacies in which antibiotics could be purchased without a prescription, across the three regions of China.

Thérèse Hesketh, from Zhejiang University and University College London (UCL), the corresponding author of the study said: "Following strong leadership by the Chinese government, antimicrobial Stewardship has improved in hospitals in China over the past 10 years, but little is known about access to antibiotics in retail pharmacies. We document the ease of access to antibiotics in pharmacies without prescriptions. Care needs to be taken to enforce the regulations around these sales, as part of wider stewardship efforts to control AMR."

The authors conducted a survey in 13 Chinese provinces, using a Simulated Patient method. From July to September 2017, forty medical students acted as real patients, presenting at pharmacies with mild upper respiratory tract symptoms, but without visible symptoms. The students recorded characteristics of the pharmacies they visited, such as location, distance from the nearest hospital and whether the pharmacy was independent or part of a chain. They also recorded details of their experience, including at which stage in the process - symptoms only described, asked for antibiotics, asked for a specific antibiotic - they were offered antibiotics.

The authors found that out of a total of 1,106 pharmacies included in the study, antibiotics could be obtained without a prescription in 925 (83.6%) cases. Of these, 279 (25.2%) gave out antibiotics with only mild symptoms being described, 576 (52.1%) gave out antibiotics when specifically asked for them and 70 (6.3%) gave out antibiotics when asked for a specific type (penicillin or cephalosporins). Of the 181 (16.4%) pharmacies in which no antibiotics were offered, the reasons given included that a prescription was necessary (113 pharmacies or 10.2%), that antibiotics were not indicated (58 pharmacies or 5.2%), or that there were no antibiotics in stock (six pharmacies or 0.5%).

The authors found no significant differences in access to antibiotics between urban or rural location of the pharmacy (city, county, township or village), or between independent pharmacies and ones that were part of a chain. However, it was easier to obtain antibiotics in pharmacies more than 2km away from a hospital.

The results suggest that, in the case of retail pharmacies, little progress has been made towards the goal to make antibiotics obtainable by prescription only by 2020. The findings raise concerns about the potential role of pharmacies in antibiotics misuse and its contribution to AMR, according to the authors. They suggest that pharmacists need to be trained to explain to customers why antibiotics are refused and that public education campaigns may be needed to raise awareness of antibiotics misuse and its consequences within the general population.

The authors caution that because the far west and far north regions of China were not included in the study, national generalizability of the findings may be limited.

Women who engage in sexual activity weekly or monthly have a lower risk of entering menopause early relative to those who report having some form of sex less than monthly, according to a new UCL study.

The researchers observed that women, who reported engaging in sexual activity weekly, were 28% less likely to have experienced menopause at any given age than women who engaged in sexual activity less than monthly. Sexual activity includes sexual intercourse, oral sex, sexual touching and caressing or self-stimulation.

The research, published in Royal Society Open Science, is based on data from the USA's Study of Women's Health Across the Nation (SWAN). It's the largest, most diverse and most representative longitudinal cohort study available to research aspects of the menopause transition.

First author on the study, PhD candidate Megan Arnot (UCL Anthropology), said: "The findings of our study suggest that if a woman is not having sex, and there is no chance of pregnancy, then the body 'chooses' not to invest in ovulation, as it would be pointless. There may be a biological energetic trade-off between investing energy into ovulation and investing elsewhere, such as keeping active by looking after grandchildren.

"The idea that women cease fertility in order to invest more time in their family is known as the Grandmother Hypothesis, which predicts that the menopause originally evolved in humans to reduce reproductive conflict between different generations of females, and allow women to increase their inclusive fitness through investing in their grandchildren."

During ovulation, the woman's immune function is impaired, making the body more susceptible to disease. Given a pregnancy is unlikely due to a lack of sexual activity, then it would not be beneficial to allocate energy to a costly process, especially if there is the option to invest resources into existing kin.

The research is based on data collected from 2,936 women, recruited as the baseline cohort for the SWAN study in 1996/1997.

The mean age at first interview was 45 years old. Non-Hispanic Caucasian women were most represented in the sample (48%), and the majority of women were educated to above a high school level. On average they had two children, were mostly married or in a relationship (78%), and living with their partner (68%).

The women were asked to respond to several questions, including whether they had engaged in sex with their partner in the past six months, the frequency of sex including whether they engaged in sexual intercourse, oral sex, sexual touching or caressing in the last six months and whether they had engaged in self-stimulation in the past six months. The most frequent pattern of sexual activity was weekly (64%).

None of the women had yet entered menopause, but 46% were in early peri-menopause (starting to experience menopause symptoms, such as changes in period cycle and hot flashes) and 54% were pre-menopausal (having regular cycles and showing no symptoms of peri-menopause or menopause).

Interviews were carried out over a ten-year follow-up period, during which 1,324 (45%) of the 2,936 women experienced a natural menopause at an average age of 52.

By modelling the relationship between sexual frequency and the age of natural menopause, women of any age who had sex weekly had a hazard ratio of 0.72, whereas women of any age who had sex monthly had a hazard ratio of 0.81.

This provided a likelihood whereby women of any age who had sex weekly were 28% less likely to experience the menopause compared to those who had sex less than monthly. Likewise, those who had sex monthly were 19% less likely to experience menopause at any given age compared to those who had sex less than monthly.

The researchers controlled for characteristics including oestrogen level, education, BMI, race, smoking habits, age at first occurrence of menstruation, age at first interview and overall health.

The study also tested whether living with a male partner affected menopause as a proxy to test whether exposure to male pheromones delayed menopause. The researchers found no correlation, regardless of whether the male was present in the household or not.
Last author, Professor Ruth Mace (UCL Anthropology), added: "The menopause is, of course, an inevitability for women, and there is no behavioural intervention that will prevent reproductive cessation. Nonetheless, these results are an initial indication that menopause timing may be adaptive in response to the likelihood of becoming pregnant."

DALLAS - Jan. 14, 2020 - Researchers at UT Southwestern have uncovered evidence that the higher prevalence of "malignant" enlargement of the heart among blacks contributes to the higher incidence of heart failure in this population. The new study is published online in the journal Circulation.

Left ventricular hypertrophy or LVH is the enlargement and thickening of the muscular wall of the left ventricle of the heart, the lower left chamber. This thickening can be detected on an electrocardiogram or with imaging tests like an echocardiogram. LVH can occur in several forms. In about half of cases, LVH occurs without other evidence of heart damage or stress, and in these cases the prognosis appears to be benign and similar to people without LVH. In contrast, in the other half of cases, when LVH occurs together with signs of damage or stress to the heart muscle, the course is malignant and associated with a markedly higher risk of heart failure.

"Malignant LVH is easily identifiable with widely used tests in the clinic, so now that we've found this association, we are hoping to identify patients with higher risk for heart failure earlier, when preventive interventions can have a greater impact on future risk," says James de Lemos, M.D., a professor of internal medicine at UT Southwestern Medical Center.

Previous studies described a malignant type of left ventricular hypertrophy but did not include enough participants to enable researchers to conclude whether the observed differences in malignant LVH contribute to a higher risk of heart failure for black versus white individuals. So the UT Southwestern researchers pooled data from three biracial cohort studies - the Atherosclerosis Risk in Communities (ARIC) Study, the Dallas Heart Study, and the Multi-Ethnic Study of Atherosclerosis (MESA) - to test the hypothesis that malignant LVH may contribute to disparities in heart failure risk.

Combined, the three studies encompassed health data from more than 26,000 people living in North Carolina, Mississippi, Minnesota, Maryland, Illinois, California, New York, and Texas. All three studies included height, weight, blood pressure, and blood test results as well as electrocardiogram results, a measure of the electrical activity of the heart. For this study, the researchers excluded participants with cardiovascular or kidney disease and those who were not self-identified as white or black, which resulted in a study group of 15,710 participants. The median age was 57 years with 56 percent female, 32 percent black, and 36 percent with hypertension.

Individuals with left ventricular hypertrophy were identified by ECG, and the malignant form of LVH was further defined as having abnormal blood marker levels reflecting injury or stress to the heart muscle. For blood markers, the researchers looked for abnormal high-sensitivity cardiac troponin levels or abnormal N-terminal pro-brain natriuretic peptide levels.

Using these characteristics, the team classified all study participants into groups based on whether they had ECG-LVH and abnormal blood markers. Then they determined how many of these participants had been hospitalized or had died due to a heart failure event in the 10 years of follow-up.

Nine percent of participants had LVH, 27 percent had abnormal cardiac troponin, and 21 percent had abnormal pro-brain natriuretic peptide levels. Of those participants with LVH, 47 percent had normal biomarker levels, 37 percent had one abnormal biomarker, and 15 percent had abnormal levels of both biomarkers.

The team found that participants with malignant LVH were older, more likely to be male, with diabetes, hypertension, and high blood pressure compared with those without LVH or those with LVH but normal blood tests. They also found that the prevalence of malignant LVH was three times higher among black men and women compared with white men and women.

Heart failure occurred in 512 participants (3.3 percent) over the 10 year study period. Of those, 56 percent were men and 39 percent were black. The rates of heart failure were highest for black men, intermediate for white men and black women, and lowest among white women. Of the participants with malignant LVH, 13 percent developed heart failure compared with 2.7 percent in the group with LVH and normal biomarkers.

"Our study helps explain why African American men and women have disproportionately high rates of heart failure, a significant health disparity that persists despite considerable advances in cardiovascular care," says Alana Lewis, M.D., a cardiology fellow at UT Southwestern Medical Center and lead author of the study. "We hope these findings can help cardiologists identify those at higher risk for developing heart failure and intervene earlier."

Bottom Line: This randomized clinical trial among more than 400 men with early-stage prostate cancer looked at whether a telephone-based program encouraging increased vegetable consumption would decrease cancer progression over two years. The authors report no significant decrease in the risk of prostate cancer progression among men in the intervention program compared with those who received only written information about diet and prostate cancer. The study may have been underpowered to identify a clinically important difference.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: J. Kellogg Parsons, M.D., M.H.S., UC San Diego Moores Comprehensive Cancer Center and VA San Diego Healthcare System, La Jolla, California, and coauthors.

(doi:10.1001/jama.2019.20207)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Osaka, Japan - A loved one suffering cardiac arrest is an emotionally stressful time for families, but never more so than when the patient is a child. The very real potential for loss of life in these situations means that the way in which emergency responders treat out of hospital cardiac arrest (OHCA) becomes even more crucial when dealing with pediatric patients.

Studies in adults have suggested that early administration of epinephrine results in more favorable outcomes for patients following cardiac arrest. Epinephrine, or adrenaline as it is more commonly known, is a hormone that increases diastolic pressure, essentially getting blood flowing again. However, there is conflicting evidence that epinephrine administration may in fact be detrimental, as it can also cause fatal arrhythmia in the heart, triggering further cardiac arrests.

Interestingly, although current international guidelines suggest that epinephrine be administered to pediatric OHCA patients with non-shockable rhythms—basically those cases where artificial defibrillation wouldn't work—there is little evidence to either support or dispute its effectiveness.

In a study published in Journal of the American College of Cardiology, an international team of researchers addressed this knowledge gap by evaluating epinephrine use during resuscitation attempts in Japanese patients to better inform the development of guidelines for treatment of pediatric OHCA.

"We were concerned by the lack of randomized controlled trials and observational studies assessing the effectiveness of epinephrine administration in pediatric OHCA cases," explains senior author of the study Tetsuhisa Kitamura from Osaka University's Graduate School of Medicine. "To better assess the effects of prehospital epinephrine administration, we retrospectively analyzed data from 3,961 OHCA patients aged between 8 and 17 years from the nationwide All-Japan Utstein Registry of the Fire and Disaster Management Agency database."

After excluding patients who did not meet the study criteria, the remaining epinephrine-treated patients were matched with patients who were candidates for epinephrine administration at the same timepoint during resuscitation but who did not receive treatment. The researchers then assessed the efficacy of epinephrine administration in the 304 patients and their matched controls based on 1-month survival and favorable neurological outcome.

"Our results showed that prehospital epinephrine administration was associated with improved return of circulation in pediatric patients with OHCA who did not respond to basic life support," says Dr Kitamura. "While we did not see any significant improvement in 1-month survival rates as a result of prehospital epinephrine administration, the return of blood flow is a necessary step in achieving a favorable neurological outcome. Therefore, we recommend that prehospital epinephrine administration should be included in international guidelines for cardiopulmonary resuscitation to enhance the survival of pediatric OHCA patients."

A Rutgers-led team may have found the key to preventing Duchenne muscular dystrophy (DMD)-related heart disease, the leading cause of death in patients living with the disease.

The study, published in the Journal of Clinical Investigation (JCI), examined the role of Connexin-43 (Cx43), a protein that regulates heart function. The researchers found that Cx43 was dysfunctional in both human and mouse DMD hearts, so they modified the Cx43 protein in the hopes of alleviating heart disease. The researchers discovered that altering the Cx43 protein through a process called phosphorylation protected DMD mice against irregular heart beat and late-stage failure.

"For many DMD patients, the heart muscles gradually break down, leading to death. Our findings may help give hope to millions of patients," said study co-author Diego Fraidenraich, an assistant professor of Cell Biology and Molecular Medicine at Rutgers New Jersey Medical School.

"Medical advances have managed to slow down the disease progression in most muscles in the body, but there are yet to be any discoveries that target or prevent deterioration of the DMD heart, which remains the number one killer among these patients," said co-author Eric Himelman, a PhD candidate at Rutgers New Jersey Medical School. "Therapies based on our finding may help prolong the lives of muscular dystrophy and other heart disease patients."

DMD, a genetic disorder characterized by progressive muscle degeneration, is the most common type of muscular dystrophy, affecting about one in 5,000 males and typically beginning at about age 4. The average life expectancy is 26.

These findings were simultaneously published together in JCI insight with another Rutgers-led study that examined Cx43 activity in the heart

Next steps include developing drugs that directly target Cx43 in DMD hearts, with a goal of potentially introducing clinical trials using Cx43 modification as a therapy for DMD patients.

The study was funded by the National Institutes of Health, the Muscular Dystrophy Association and the American Heart Association, and includes an interdisciplinary team of investigators with complementary expertise from Rutgers University, Fred Hutchinson Cancer Research Center, New York University and Baylor College of Medicine.

Quicker is not always better, especially when it comes to a 3D sensor in advanced technology. With applications in autonomous vehicles, robots and drones, security systems and more, researchers are striving for a 3D sensor that is compact and easy to use.

A team from Yokohama National University in Japan believes they have developed a method to obtain such a sensor by taking advantage of slow light, an unexpected move in a field where speed is often valued above other variables.

They publish their results on January 20 in the Optica, a journal published by The Optical Society.

Light detection and ranging also called LiDAR sensors can map the distance between distant objects and more using laser light. In modern LiDAR sensors, many of the systems are composed of a laser source; a photodetector, which converts light into current; and an optical beam steering device, which directs the light into the proper location.

"Currently existing optical beam steering devices all use some kind of mechanics, such as rotary mirrors," said Toshihiko Baba, paper author and professor in the Department of Electrical and Computer Engineering at Yokohama National University. "This makes the device large and heavy, with limited overall speed and a high cost. It all becomes unstable, particularly in mobile devices, hampering the wide range of applications."

In recent years, according to Baba, more engineers have turned toward optical phased arrays, which direct the optical beam without mechanical parts. But, Baba warned, such an approach can become complicated due to the sheer number of optical antennae required, as well as the time and precision needed to calibrate each piece.

"In our study, we employed another approach -- what we call 'slow light,'" Baba said.

Baba and his team used a special waveguide "photonic crystal," aimed through a silicon-etched medium. Light is slowed down and emitted to the free space when forced to interact with the photonic crystal. The researchers engaged a prism lens to then direct the beam in the desired direction.

"The non-mechanical steering is thought to be crucial for LiDAR sensors," Baba said.

The resulting method and device are small-sized, free of moving mechanics, setting the stage for a solid-state LiDAR. Such a device is considered smaller, cheaper to make and more resilient, especially in mobile applications such as autonomous vehicles.

Next, Baba and his team plan to more fully demonstrate the potential of a solid-state LiDAR, as well as work on improving its performance with the ultimate goal of commercializing the device.

Overall, Swedish 70-year-olds' eyesight is good, but many could see even better. Six in ten can improve their vision by getting eyeglasses or changing the power of the glasses they already have, according to a new study from the University of Gothenburg.

"We're really healthy and have good eyesight in Sweden, and being 70 doesn't have to mean your vision is poor. It's easy to get it checked by an optician, who can offer the right glasses or refer you to an ophthalmologist if necessary," says Lena Havstam Johansson, PhD student at Sahlgrenska Academy, University of Gothenburg, and ophthalmic nurse at Sahlgrenska University Hospital.

In the study, the great majority of 70-year-olds were content with their eyesight, but many overestimated how well they can actually see. More than half (61.5 percent) proved able to see considerably better by getting glasses or changing the power of the ones they already had.

"Visual impairment can creep up on you, making it difficult to notice that your eyes are getting worse. So it's a good idea to visit an optician regularly when you get older, even if you don't feel your sight is deteriorating," Havstam Johansson says.

The study shows that how people perceive their own eyesight corresponds poorly with reality. Of those whose vision had deteriorated, the majority nonetheless regarded their eyesight as good.

"Above all, it was reduced contrast sensitivity that made people think their sight was poor. Impaired visual acuity or visual field defects had less of an impact on how they perceived their own eyesight," says Madeleine Zetterberg, Professor of Ophthalmology at the University of Gothenburg's Sahlgrenska Academy and coauthor of the study.

The study covers 1,200 Gothenburg residents who had all answered a special "self?reported ocular morbidity questionnaire" on how they perceived their eyesight and thought their everyday lives were being affected by vision problems.

In cooperation with a colleague, Lena Havstam Johansson also investigated the eyesight of nearly half (560) of these 70-year-olds, in several ways. They examined the study participants' central vision (the part we use when we watch TV or look at a painting, for example), their peripheral vision (the part that enables us to pick up what is going on outside our field of focus), and their ability to perceive contrasts (contrast sensitivity). In addition, every study participant's lens and retina were photographed to detect eye disease, if any.

Having glasses of incorrect power was equally common in men and women in the study but, in general, the men had slightly better eyesight than the women. This may be explained partly by the higher prevalence of cataract among women generally. This was confirmed in the present study: Just over 27 percent of the women had cataract, but only just over 19 percent of the men. Many respondents who proved to have cataract were already aware that they had this eye disease, while others learned of it when they had their eyes tested. The most common eye disease among the study participants examined was cataract (23.4%), followed by age-related macular degeneration (AMD, 4.7%) and glaucoma (4.3%), while 1.4% had diabetic retinopathy (retinal changes due to diabetes).

These and other findings of the present study were recently accepted for publication in the scientific journal Acta Ophthalmologica. The study forms part of the H70 population-based study of aging and its diseases that has been underway at the University of Gothenburg since the early 1970s. This H70 study provides a picture of the trends of life and health among ordinary 70-year-olds, and also scope for comparing what getting older has been like for different generations.

Initial results from treating endometriosis in mice with cannabinoids suggest they can alleviate some symptoms of the disease, according to a new study in the open-access journal eLife.

The findings have led to the start of a clinical trial in collaboration with the Gynecology Service of the Hospital Clinic of Barcelona, Spain. This trial will evaluate the possible benefits of the naturally occurring cannabinoid Δ9-tetrahydrocannabinol (THC; the main psychoactive constituent of the cannabis plant) in women with endometriosis.

Endometriosis is a common, chronic and painful disease caused when the lining of the womb - the endometrium - grows outside of the womb cavity. These growths affect reproductive organs and can cause pain, infertility, anxiety, depression and result in a considerable impact on quality of life. Treatment options include surgery or hormone therapy, but these are not always effective and often have significant side-effects.

"With a lack of effective treatments, women with endometriosis usually rely on self-management strategies like dietary changes or exercise," explains senior author Rafael Maldonado, Professor at the University Pompeu Fabra of Barcelona, Spain. "Although cannabis comes with a large number of potential side effects, its medicinal properties could provide pain relief in endometriosis and other conditions.

"Since medical THC is available in some countries, the findings of our study may be of interest for gynecologists and pain specialists who manage the treatment of women with endometrial pain. But it is crucial to underline that the use of cannabis in unregulated scenarios should be discouraged given the serious risks associated with its consumption."

The team studied mice with endometrial implants in their pelvis to mimic endometriosis in humans. Those with the implants were more sensitive to pain in their pelvis that can also be associated with emotional and cognitive alterations - similar to symptoms seen in some women with endometriosis.

They treated the mice with a daily dose of 2mg/kg THC for 28 days. This alleviated the pain sensitivity in the pelvis but had no effect on pain in other areas, mainly the hind leg paw, showing that the treatment was specific to pain caused by endometriosis. The pain relief also occurred regardless of when the treatment was started, suggesting that it worked just as well once pain symptoms were established.

The team next found that mice with endometriosis had similar anxiety-like symptoms experienced by some women with the condition. This was measured by the amount of time the animals spent in open areas of a maze, as those with higher anxiety levels tend not to explore too far. However, their experiments could not reveal whether THC had any significant effects in treating this anxiety.

As endometriosis can be known to impair cognitive function in some women, the team also studied memory performance in the mice. They provided the animals with two identical objects and allowed them to become familiar with them. They then replaced one of the objects and timed how long the mice spent exploring the new versus familiar object, to give an indication of what the animals remembered. They found that memory was impaired in the mice with endometriosis compared with those that did not have the condition. However, mice treated with THC did not show this impairment, suggesting that THC may have a protective effect.

Finally, the team studied the effects of THC on the endometrium inside and outside of the womb, and found that mice with endometriosis treated with THC for 32 days had smaller endometrial growths.

"Together, our findings show that THC limits the development and symptoms of endometriosis in an experimental model and highlight the interest of conducting further research to ensure the safety and beneficial effects of this treatment in women with endometriosis," concludes first author Alejandra Escudero-Lara, a PhD student at the University Pompeu Fabra of Barcelona, Spain.