Culture

CHICAGO, September 25, 2018 - For individuals carrying a genetic mutation that causes Alzheimer's disease, engaging in at least 2.5 hours of physical activity per week may have beneficial effects on markers of Alzheimer's disease brain changes and may delay cognitive decline, according to a new study available online by Alzheimer's & Dementia: The Journal of the Alzheimer's Association as an article in press, corrected proof.

According to the authors, these results support the benefit of physical activity on cognition and dementia progression, even in individuals with autosomal dominant* Alzheimer's disease (ADAD), a rare genetically-driven form of the disease in which the development of dementia at a relatively young age is inevitable.

The authors say their results, "show a significant relationship between physical activity, cognition, functional status and Alzheimer's disease pathology even in individuals with genetically-driven ADAD. ... The officially recommended physical activity duration of ?150 minutes per week was associated with significantly better cognition and less Alzheimer's disease pathology in ADAD. From a public health perspective, this amount of physical activity was achieved by 70% of all ADAD individuals participating at the DIAN study. Therefore, a physically active lifestyle is achievable and may play an important role in delaying the development and progression of ADAD."

"The results of this study are encouraging, and not only for individuals with rare genetically-caused Alzheimer's disease," said Maria C. Carrillo, Ph.D., Chief Science Officer for the Alzheimer's Association. "If further research confirms this relationship between physical activity and later onset of dementia symptoms in ADAD, then we need to expand the scope of this work to see if it also is true in the millions of people with more common, late onset Alzheimer's."

Christoph Laske, M.D. and his research team at the University Hospital of Tübingen, Germany analyzed data generated from 275 individuals (average age 38.4) who carry a genetic mutation for ADAD and are participating in the Dominantly Inherited Alzheimer's Network (DIAN), an international observational study of individuals and families with ADAD led by researchers at Washington University School of Medicine in St. Louis.

Researchers aimed to determine if at least 150 minutes of physical activity (walking, running, swimming, aerobics, etc.) per week - the current recommendation by the World Health Organization and the American College of Sports Medicine - would produce cognitive benefits for the study participants. One hundred fifty-six (156) were classified as high physical activity individuals (>150 minutes physical activity/week); 68 as low physical activity individuals (

Researchers found individuals who engaged in more physical activity scored better on the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SOB), which are well-accepted standard measures of cognition and function. Similarly, individuals who exercised more had lower levels of Alzheimer's disease biomarkers in cerebrospinal fluid, including lower tau, a protein that builds up in the brains of people living with Alzheimer's disease. However, individual trajectories of cognitive changes have not been assessed in this cross-sectional study.

"A physically active lifestyle is achievable and may play an important role in delaying the development and progression of ADAD. Individuals at genetic risk for dementia should therefore be counselled to pursue a physically active lifestyle," the study authors conclude.

"There is a growing and increasingly strong body of scientific evidence of the beneficial impact of lifestyle factors in reducing the risk for, and perhaps even preventing, cognitive decline and dementia," Carrillo said. "For example, at AAIC 2018 in July we heard preliminary results of SPRINT MIND, the first randomized clinical trial to demonstrate that intensive blood pressure treatment reduces new cases of mild cognitive impairment (MCI), and the combined risk of MCI plus all-cause dementia. This adds credibility to the vision of future Alzheimer's therapy that combines drugs and modifiable risk factor interventions -- as we do now in heart disease."

To more definitively generate scientific evidence on how lifestyle choices affect brain health, the Alzheimer's Association is currently leading a large two-year clinical trial called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER). The study is a two-year clinical trial to evaluate whether lifestyle interventions that simultaneously target many risk factors protect cognitive function in older adults who are at increased risk for cognitive decline. U.S. POINTER is the first such study to be conducted in a large group of Americans across the United States.

"Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer`s disease," by Dr. Stephan Muller, et al, was supported by The Dominantly Inherited Alzheimer's Network (DIAN, U19AG032438), U.S. National Institute on Aging, German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Japan Agency for Medical Research and Development, AMED, and Korea Health Industry Development Institute (KHIDI).

Forty per cent of older adults who leave hospital are discharged to home care or a long-term care facility, which, combined with where they lived before hospitalization, affects their risk of readmission, found a study published in CMAJ (Canadian Medical Association Journal).

These data are important for both health care professionals and policy-makers to improve discharge planning for patients and to reduce readmissions.

"The information from this study will contribute to a better understanding of the extent to which complicated transitions to and from hospital influence readmission among older adults, which is essential for system planning, performance measurement, and the targeting and testing of interventions to improve transitions and reduce readmissions," writes Dr. Andrea Gruneir, Department of Family Medicine, University of Alberta and ICES, with coauthors.

While most research on readmissions focuses on people who are admitted to hospital from the community and who return to the community, this study considers the large number of older adults with more complex pathways across the system.

The large study of 701,527 hospitalized adults over age 65 in Ontario found that 31.5% of people were discharged to home care and 9.5% to long-term care, with 3% newly admitted to long-term care. More than half (53.5%) were women and 40% had five or more chronic conditions. Almost every patient (98%) had visited a doctor at least once during the year before hospital admission, 331,168 (47%) had visited the emergency department and 72,536 (10%) had been admitted.

The authors state that the study "shows that fundamental shortcomings in the health system's ability to meet older adults' needs, particularly those with dementia, manifest as frequent use of acute care, including readmissions, prolonged hospital stays with extended alternate levels of care periods and 'non-acute' reasons for hospital admission."

People who were discharged with home care were the most likely to be readmitted, and when readmitted, 19% were there for two or more weeks and nearly 20% were designated as alternate level of care (ALC), the longest of any group in the study. Conversely, people who were discharged to long-term care (as a new admission) were the least likely to be readmitted, but their first hospital stay was most often for dementia. More than 80% were in hospital for two or more weeks and were designated as ALC, which means they no longer need acute hospital care but can't be discharged as the appropriate level of care required is not available in another setting.

"By contextualizing hospitalization within these care settings, our findings suggest an approach to understanding readmissions as a signal of the health system's preparedness for the ageing population," the authors conclude.

SEATTLE - The United States ranks 27th in the world for its investments in education and health care as measurements of its commitment to economic growth, according to the first-ever scientific study ranking countries for their levels of human capital.

The nation placed just behind Australia (ranked 26th) and just ahead of Czech Republic (ranked 28th). In contrast, China's ranking of 44th in 2016 represents an increase from its 1990 ranking of 69th.

"The decline of human capital in the United States was one of the biggest surprises in our study," said Dr. Christopher Murray, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. "Our findings show the association between investments in education and health and improved human capital and GDP - which policymakers here in the US ignore at their own peril. As the world economy grows increasingly dependent on digital technology, from agriculture to manufacturing to the service industry, human capital grows increasingly important for stimulating local and national economies."

The World Bank President, Dr. Jim Yong Kim, defines human capital as "the sum total of a population's health, skills, knowledge, experience, and habits." It is a concept that recognizes that not all labor is equal, and the quality of workers can be improved by investing in them.

The US's ranking of 27th in 2016 represents a significant decrease from its 1990 ranking of 6th. It comes from having 23 years of expected human capital, measured as the number of years a person can be expected to work in the years of peak productivity, taking into account life expectancy, functional health, years of schooling, and learning.

Overall, US residents had 43 out of a possible 45 years between the ages of 20 and 64; expected educational attainment of 12 years out of a possible of 18 years in school; and a learning score of 89 and a functional health score of 88, both out of 100. Learning is based on average student scores on internationally comparable tests. Components measured in the functional health score include: stunting, wasting, anemia, cognitive impairments, hearing and vision loss, and infectious diseases, such as HIV/AIDS, malaria, and tuberculosis.

"Clearly, China is on an upward trajectory, while the US, without more strategic investments, especially in education, risks falling behind even further," Murray said.

Kim has stated that measuring and ranking countries by their human capital will enable comparisons over time, thereby providing governments and investors insights into where critical investments are needed to improve health and education. Last year, he asked IHME to develop such a measurement.

"Measuring and ranking countries by their level of human capital is critical to focus governments' attention on investing in their own people," Kim said. "This study from IHME is an important contribution to the measurement of human capital across countries and over time."

The study, "Measuring human capital: A systematic analysis of 195 countries and territories, 1990 to 2016," was published in the international medical journal The Lancet. It is based on a systematic analysis of an extensive array of data from numerous sources, including government agencies, schools, and health care systems.

The study places Finland at the top. Turkey showed the most dramatic increase in human capital between 1990 and 2016; Asian countries with notable improvement include China, Thailand, Singapore, and Vietnam. Within Latin America, Brazil stands out for improvement. All these countries have had faster economic growth over this period than peer countries with lower levels of human capital improvement.

In addition, the greatest increase among sub-Saharan African countries was in Equatorial Guinea. Some of the world's most rapid improvements were in the Middle East, including Saudi Arabia and Kuwait.

Over the past quarter century, there has been limited progress in building human capital in selected countries that started at a high baseline. The US was ranked sixth in human capital in 1990 but dropped to 27th in 2016 because of minimal progress, particularly in educational attainment, which declined from 13 years to 12.

Health and education advocates, economists, and others should use the findings as evidence to argue for greater attention to - and resources for - improving their nations' human capital.

"Underinvesting in people may be driven by lack of policy attention to the levels of human capital," Murray said. "No regular, comparable reporting across all countries on human capital currently exists. Such reporting over the next generation - as a way to measure investments in health and education - will enable leaders to be held accountable to their constituents."

Researchers found that nations with greater improvements in human capital also tend to have faster growth in per capita GDP. Countries in the highest quartile of improvements in human capital between 1990 and 2016 had a 1.1% higher median yearly GDP growth rate than countries in the bottom quartile of human capital improvements. For example, between 2015 and 2016, a 1.1% increase in the human capital growth rate in China equated to an additional $163 per capita; in Turkey, $268 per capita; and in Brazil, $177 per capita.

The study focuses on the number of productive years an individual in each country can be expected to work between the ages of 20 to 64, taking into account years of schooling, learning in school, and functional health. The calculation is based on systematic analysis of 2,522 surveys and censuses providing data on years of schooling; testing scores on language, math, and science; and health levels related to economic productivity.

Among other findings:

At the top of the listing of 195 nations, Finland's level of expected human capital in 2016 was 28 years, followed immediately by Iceland, Denmark, the Netherlands (each with 27 years), and Taiwan (26 years).

Niger, South Sudan, and Chad all ranked lowest in 2016 at 2 years, followed by Burkina Faso and Mali (each with 3 years).

In 2016, 44 countries surpassed more than 20 years of expected human capital, while 68 countries had fewer than 10 years.

Rankings for the 10 most populous countries in 2016, in addition to China, India, and the United States were Indonesia (131st), Brazil (71st), Pakistan (164th), Nigeria (171st), Bangladesh (161st), Russia (49th), and Mexico (104th).

There were notable differences in expected human capital by sex in 2016. Across the board, expected years lived between 20 and 64 years are greater in females than in males. In addition, health status tends to be higher among females than males, with the exception of high-income countries. In terms of the overall measure, for countries below 10 years of expected human capital, rates of human capital tend to be higher in males, while countries above 10 years tend to have higher expected human capital for females.

Termite colonies have been found to thrive and reproduce without males, new research from the University of Sydney reveals.

The findings provide new evidence that males aren't required to maintain some advanced animal populations. They add momentum to questions about the impact and function of males in animal societies.

It is well known that many hymenopteran insect species - which include bees and ants - are essentially all-female societies. But termites are from a different insect order and typically contain male and female reproductives and workers.

Population analysis by a team of researchers - including Professor Nathan Lo and postdoctoral researcher Dr Toshihisa Yoshiro from the University's School of Life and Environmental Sciences - has for the first time identified termite colonies that completely lack males.

Findings published in BMC Biology today showed six of 10 termite populations scrutinized by the researchers in Japan were entirely comprised of asexual females. Aside from a lack of males, the colonies' queens contained no sperm in their sperm storage organs and their eggs remained unfertilised. Furthermore, there was no significant difference in the hatching rate of these unfertilised eggs and that of fertilised eggs among mixed-sex termite populations.

All the populations studied were of the Glyptotermes nakajimai species based in Japan. This species typically inhabits forest areas and is not considered a pest.

"These results demonstrate males are not essential for the maintenance of animal societies in which they previously played an active social role," said Professor Lo.

The occasional development of unfertilised eggs in mixed-sex colonies suggests asexual female populations may have evolved from their mixed-sex counterparts.

Professor Lo says asexual reproduction could allow termites to successfully adapt to a range of new environments.

"All else being equal, asexual populations grow at twice the rate of sexual populations because only females are required to reproduce. This increased growth rate of colonies makes it easier for populations to entrench themselves in new environments."

While it is possible some of the 276 termite species in Australia, among the most primitive and ecologically diverse in the world, reproduce asexually further research is required to determine this, Dr Yashiro said.

Loss of males from mixed-sex societies in termites was co-written by researchers from the Laboratory of Insect Ecology at Kyoto University.

USC scientists say Alzheimer's could be diagnosed earlier if scientists focus on an early warning within the brain's circulation system.

That's important because researchers believe that the earlier Alzheimer's is spotted, the better chance there is to stop or slow the disease.

"Cognitive impairment, and accumulation in the brain of the abnormal proteins amyloid and tau, are what we currently rely upon to diagnose Alzheimer's disease, but blood-brain barrier breakdown and cerebral blood flow changes can be seen much earlier," said Berislav Zlokovic, the Mary Hayley and Selim Zilkha Chair in Alzheimer's Disease Research at the Keck School of Medicine of USC. "This shows why healthy blood vessels are so important for normal brain functioning."

In a new review article in the Sept. 24 issue of Nature Neuroscience, Zlokovic and his colleagues recommend that the blood-brain barrier, or BBB, be considered an important biomarker -- and potential drug target -- for Alzheimer's disease. Because Alzheimer's is irreversible, and not fully understood, understanding the first step in the disease process is a critical step in fighting it.

Alzheimer's afflicts 5.7 million Americans and is expected to impair about 14 million by 2050, according to the U.S. Centers for Disease Control and Prevention. Treatment costs total hundreds of billions of dollars annually in the United States. Alzheimer's kills more people than breast cancer and prostate cancer combined.

The blood-brain barrier is a filtration system, letting in good things (glucose, amino acids) and keeping out bad things (viruses, bacteria, blood). It's mostly comprised of endothelial cells lining the 400 miles of arteries, veins and capillaries that feed our brains.

Some evidence indicates that leaks in the blood-brain barrier may allow a protein called amyloid into the brain where it sticks to neurons. This triggers the accumulation of more amyloid, which eventually overwhelms and kills brain cells.

"Something is off with the system when that happens," said Arthur Toga, director of the Laboratory of Neuro Imaging (LONI) and the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. "Healthy people have amyloid in their bodies. When the system is dysregulated, amyloid can build up and cells die off."

Blood-to-brain leaks are seen in other neurodegenerative diseases, such as Huntington's disease, Parkinson's and multiple sclerosis.

BBB leaks can be detected with an intravenously administered contrast substance in concert with magnetic resonance imaging. Brain microbleeds, another sign of leakage, also can be picked up with MRI. A slowdown in the brain's uptake of glucose, visible via PET scan, can be a another result of BBB breakdown.

Zlokovic notes that these aren't tests routinely offered at a doctor's office.

FINDINGS

Researchers examined participation and weight loss results in an online diabetes prevention program; an in-person diabetes prevention program; and the Veterans Administration's face-to-face standard-of-care weight management program, called MOVE!

In the primary analysis, enrollees in the online diabetes prevention program saw a mean weight loss of 10.3 pounds at 6 months and 8.8 pounds at 12 months. In a secondary analysis of participants who completed one or more modules/sessions, mean weight loss for online participants was 10.6 pounds at six months and 9 pounds at one year. This was roughly comparable to the results of in-person participants, but significantly higher than it was for MOVE! participants in at least one meeting, who lost 1.1 pounds at six months and 10.6 pounds at one year. In addition, the researchers found that the online program had better participation than the in-person program, with 87 percent of online participants completing eight or more sessions, compared with 59 percent for the in-person program and 55 percent for MOVE!

This study is one of the first to assess weight outcomes in an online diabetes prevention program in comparison to in-person delivery of such a program.

BACKGROUND

Some 84 million, or one in three, U.S. adults have prediabetes, a condition in which one's blood sugar levels are consistently higher than normal, though not high enough to be type 2 diabetes. Without any intervention, up to 30 percent of adults with prediabetes can develop type 2 diabetes within five years, and up to 70 percent can develop it over their lifetime. Yet type 2 diabetes risk can be lowered by as much as 58 percent with lifestyle interventions such as diabetes prevention programs.

METHOD

The trial enrolled 268 obese or overweight veterans with prediabetes in an online program. In a separate trial, 273 were enrolled in an in-person program, and 114 were enrolled in MOVE! This study included only veterans, but participants were recruited from four large centers and were diverse. Participants were not randomly placed in a group and recruitment processes differed between the online and in-person programs.

The online program, developed by Omada Health, consisted of virtual groups of participants; live e-coaches who monitored group interactions and provided the participants with feedback via phone and private online messages; weekly educational modules on healthy eating and exercise; and wireless scales to record participant weights. The in-person program consisted of eight to 22 group-based face-to-face sessions focused on 7 percent weight loss and at least 150 minutes per session of moderate physical activity. The MOVE! program included eight to 12 face-to-face healthy-lifestyle sessions and monthly maintenance sessions, but with no specified goals. Weight change was measured at six months and again at 12 months.

IMPACT

An intensive, multifaceted online diabetes prevention program is as effective as in-person programs and can make prevention programs more accessible to those at risk for developing diabetes.

AUTHORS

First author was Dr. Tannaz Moin, assistant professor of medicine at the David Geffen School of Medicine at UCLA and core investigator at Veterans Affairs' Health Services Research & Development Center for the Study of Healthcare Innovation, Implementation and Policy. Other researchers were from the Veterans Administration, Duke University, Medical College of Wisconsin, University of Maryland, University of Minnesota and University of Michigan.

JOURNAL

The American Journal of Preventive Medicine published this study.

GRAND RAPIDS, Mich. (September 24, 2018) -- A team led by Van Andel Research Institute (VARI) scientists has revealed for the first time the atomic-level structure of TRPM2, a protein that may be a promising drug target for conditions such as Alzheimer's disease and bipolar disorder.

TRPM2 is found throughout the body and is integrally involved in regulating core body temperature, mediating immune responses and governing apoptosis, the programmed death of cells. It is activated by range of stimuli including oxidative stress, which results from chemical imbalances and is linked to numerous neurological conditions.

"TRPM2 is absolutely critical for healthy function but, until today, we were missing key insights into its structure and mechanism of action," said Juan Du, Ph.D., an assistant professor at VARI and co-senior author on a study describing TRPM2's structure, published today in Nature "It is our hope that these findings will act as a schematic for designing better and desperately needed medications for a host of neurological conditions."

The atomic-level images of TRPM2 depict a bell-like structure, with a transmembrane domain region on the bell's shoulder and an expanded NUDT9-H domain on the bell's lip. They also reveal a novel drug binding site for ADPR, a messenger molecule associated with oxidative stress and metabolism, which overturns the prevailing view that TRPM2 binds ADPR at the NUDT9-H domain. These revelations provide valuable details that could inform the design of therapeutic drugs to treat temperature-related diseases and prevent neuronal death in neurodegenerative diseases.

"Although we have known for some time that TRPM2 is a vital component of many biological processes and a possible drug target, we didn't know exactly what it looked like or how it worked," said Wei Lü, Ph.D., an assistant professor at VARI and co-senior author. "Today's findings change that, and go a long way toward a more comprehensive understanding of these incredibly important molecules."

TRPM2 belongs to the TRP superfamily, a group of proteins that mediate responses to sensory stimuli, such as pain, pressure, vision, temperature and taste. Broadly known as ion channels, proteins like TRP nestle within cells' membranes, acting as gatekeepers for chemical signals passing into and out of the cell. The eight proteins that comprise the TRPM subfamily are part of this broader group.

To date, TRPM2 is the fourth TRPM protein to have its structure resolved at the atomic level and the second TRPM protein to be determined at atomic resolution at VARI. In December, Lü and Du revealed the structure of TRPM4, which plays a role in regulating blood supply to the brain. It was the first structure of a TRPM protein determined at atomic resolution.

The findings were made possible by VARI's state-of-the-art David Van Andel Advanced Cryo-Electron Microscopy Suite, which allows scientists to view some of life's smallest components in exquisite detail. VARI's largest microscope, the Titan Krios, is so powerful that it can visualize molecules 1/10,000th the width of a human hair.

September is addiction recovery month, and, in the midst of the current opioid epidemic, it's an apt moment for addiction research experts to map the future path forward for a long-term recovery strategy for substance abuse. Warren Bickel, the director of the Virginia Tech Carilion Research Institute (VTCRI) Addiction Recovery Research Center, and Keith Humphreys, the Esther Ting Memorial Professor in psychiatry and behavioral science at Stanford University, called their colleagues to action in an article published in JAMA Psychiatry, a journal of the American Medical Association.

"More than 25 million people in the United States smoke cigarettes, and more than 20 million people meet diagnostic criteria for other substance use disorders," said Bickel, who also co-directs the VTCRI Center for Transformative Research on Health Behaviors. "That said, there are also more than 25 million Americans who have been in recovery for years, for decades. There's hope here."

Bickel pointed to the International Quit & Recovery Registry (IQRR) as an important research tool to advance understanding of long-term addiction recovery. Utilization of this tool could lead to better treatments for individuals who are not yet able to maintain long-term recovery, according to Bickel.

The IQRR, sponsored by VTCRI, has nearly 8,000 registrants from all 50 states, 40 countries, and five continents. Registrants' recovery times, from a variety of addictions, range from less than a year up to more than 20 years. Eighty-three percent of the participants identified two or more substances as their addictions of choice.

"This is the only registry of its type in the world, to my knowledge," Bickel said. To respect privacy, registrants do not have to submit their names. They are asked to provide a valid email address, zip code, and information about their addiction. "We're learning about the circumstances leading to addiction, the choices leading to recovery, and the social and cultural environments for people working through addiction."

Researchers have learned that addiction physically changes the brain, Bickel said, and ongoing research in the field has started to probe how even the briefest abstinence can change the brain further. The contributions from these studies are significant, according to Bickel and Humphreys, but they're not enough.

"There's a clear need for advancement in our knowledge of recovery processes. We need more information - basic information - about how the brain functions and heals during recovery," Bickel said. "Increasing the number of neuroscience studies and including longitudinal designs to understand how a person's brain changes after a few years or a few decades in recovery could have substantial clinical, scholarly, and public policy benefits."
Bickel and Humphreys plan to further address the questions they raised in their article, in anticipation of fostering more neuroscience research focused on long-term recovery from addiction.

"Understanding long-term recovery is important for science and for society," Humphreys said. "For science, unraveling the nature and treatment for medical disorders requires us to understand both the cause of disease, the course it takes, and the recovery--but in the addiction field, we have focused almost entirely on the first two. For society, while many people understandable despair over the horrors of the opioid epidemic, the reality of recovery gives us hope that happy and healthy lives are possible for those currently suffering."

Boston, MA - Children whose mothers use marijuana are more likely to start their own marijuana use an average of two years earlier than children whose mothers don't use the drug, according to a new study from Harvard T.H. Chan School of Public Health.

The study will be published September 24, 2018 in the American Journal of Preventive Medicine.

"Beginning marijuana use at a young age has been linked with negative cognitive and behavioral consequences," said Natasha Sokol, who led the study while a doctoral student at Harvard Chan School and is now a postdoctoral research fellow at Brown University School of Public Health's Center for Alcohol and Addiction Studies. "In a shifting regulatory environment in the U.S. in which the visibility and acceptability of adult marijuana use is expected to increase, it's important to better understand how these changes may impact children's early marijuana use so that we can better identify at-risk youth and implement effective prevention strategies."

Prohibiting marijuana isn't necessarily consistent with public health goals, according to the study authors. For example, marijuana has recognized therapeutic benefits for a number of health conditions, and may serve as a safer alternative to opioids. In addition, more than half of all drug arrests in the U.S. are marijuana-related and are a major driver of racial disparities in arrest and incarceration.

But in children who begin use at a young age, marijuana has been linked with negative consequences such as impairments in concentration and decision-making, increased impulsivity, and reductions in IQ. The younger a child is when he or she begins using marijuana, the more severe the effects, studies have suggested. Therefore, delaying marijuana initiation may be an important public health goal, the authors said.

Using data from the National Longitudinal Survey of Youth 1979 and Child and Young Adults, the new study assessed the timing and extent of marijuana use and initiation among 4,440 children and 2,586 mothers. Researchers tested for the effect of a mother's marijuana use between a child's birth and age 12 on that child's subsequent risk of marijuana initiation, controlling for factors related to the child's early life behavior and cognition and on the family's socioeconomic position and social environment.

The study found that 2,983 children (67.2%) and 1,053 mothers (35.3%) self-identified as marijuana users. Children whose mothers used marijuana were at increased risk for starting marijuana use prior to age 17, and they began using at a median age of 16, compared with age 18 for children whose mothers didn't use the drug. The association was slightly stronger among non-Hispanic non-black children.

One limitation of the study was that it did not measure whether children were aware of their mothers' marijuana use. The study also lacked data on the frequency and severity of mothers' marijuana use.

"Although more research is needed, physicians who prescribe marijuana might consider educating parents who use the drug about the potential dangers of early marijuana use among their children, and provide information and preventive strategies to delay such use," said Vaughan Rees, lecturer on social and behavioral sciences and director of Harvard Chan School's Center for Global Tobacco Control.

Ann Arbor, September 24, 2018 - When mothers use marijuana during the first 12 years of their child's life, their cannabis-using children are more likely to start at an earlier age than children of non-using mothers, according to a new study from the Harvard T.H. Chan School of Public Health published in the American Journal of Preventive Medicine. This study is the first to establish a relationship between maternal cannabis use during a child's lifetime and earlier initiation in a nationally-representative, longitudinal cohort, and examine the role of race, gender, and other social environmental factors.

"Early initiation is one of the strongest predictors of the likelihood of experiencing health consequences from marijuana use. In a shifting regulatory environment in which we expect adult marijuana use to become more normative, developing a deeper and more nuanced understanding of social risk factors for early initiation is a critical step in intervention design and delivery. Incorporating maternal cannabis use into our understanding of the important risk factors for early initiation may help us better identify at-risk youth for more tailored or intensive prevention strategies," explained lead investigator Natasha A. Sokol, ScD, currently of the Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA.

The investigators analyzed two linked cohorts of The National Longitudinal Survey of Youth 1979 (1980-1998 waves) and Child and Young Adults (1988-2014 waves) to assess the timing and extent of maternal and child marijuana use and initiation. They evaluated the data for 4,440 children and 2,586 mothers for the effect of maternal marijuana use between a child's birth and age 12 on that child's subsequent marijuana initiation, controlling for potentially important factors related to the child's early life behavior and cognition and the family's socioeconomic position and social environment. Overall, 2,983 children (67.2 percent) and 1,053 mothers (35.3 percent) self-identified as cannabis users. The investigators found that the children whose mothers used marijuana were at increased risk for marijuana initiation prior to age 17 and began at a median age of 16, compared to age 18 among children of non-users, noting that this effect was slightly stronger among non-Hispanic non-black children.

Although marijuana is generally thought to be less harmful compared with other drugs of abuse, the likelihood of experiencing health consequences associated with marijuana use is strongly linked to age at initiation, such that those who initiate earlier are at much greater risk. Negative consequences may be particularly marked for children and adolescents during these developmentally critical ages. Child and adolescent cannabis use is associated with impairments in attention, concentration, decision-making and working memory, and increased impulsivity, which may persist for weeks after use, with evidence that some cognitive effects, including reductions in IQ, may linger into adulthood. Among cannabis users, earlier initiation is associated with increased risk of anxiety and depressive disorders.

The United States is currently experiencing a sea change surrounding marijuana. This cultural shift is expected to result in increases in the prevalence, frequency, visibility, and/or acceptability of adult marijuana use. Understanding the impact of parent use on early marijuana initiation is an important step in anticipating the ways in which social environmental changes may alter the disease burden associated with marijuana in the US.

The findings indicate that children of marijuana-using parents may be an important subgroup for identification and early, evidence-based intervention by pediatricians and adolescent healthcare providers. Although future research on the mechanisms underpinning this relationship is necessary before more specific recommendations can be made, marijuana prescribers and other physicians may consider educating marijuana-using parents about early marijuana initiation and equipping them with evidence-based preventive strategies to delay marijuana use in their children. Further research may seek to understand best practices for preventing early initiation, such as decreasing or pausing use, reducing the visibility of use until children are older, and providing training, tools, and resources to help address these issues.

"Cannabis has recognized therapeutic benefits for treating a number of different medical conditions. There is also evidence that the availability of legal medical and recreational cannabis may reduce population opioid overdose deaths. Cannabis arrests account for more than half of all drug arrests in the US, and cannabis possession is a major driver of racial disparities in arrest and incarceration. For these reasons, total cannabis prohibition may not be consistent with public health objectives. Instead, given the neurocognitive, health, and social consequences associated with early use, delaying initiation may be an important, but undervalued, public health goal," commented Dr. Sokol.

(New York, NY - September 24, 2018) -- Researchers at Mount Sinai have discovered that an antimicrobial protein found in the gut can stave off a common and highly lethal side effect of bone marrow transplants, according to a study published in the Journal of Clinical Investigation in September.

The protein, regenerating islet-derived 3-alpha (REG3α), is made by cells in the lining of the gastrointestinal tract. It plays a role in a complication of bone marrow transplants called graft-versus-host-disease (GVHD), in which the donated bone marrow's immune cells attack the patient's gastrointestinal tract.

This study shows that GVHD causes increased serum levels of REG3α throughout the body while, paradoxically, decreasing the production of the protein in the gastrointestinal tract as GVHD worsens.

The Mount Sinai researchers showed that mice that could not make the protein did not survive GVHD, but also found that adding REG3α to human gastrointestinal cell lines prolonged their survival, confirming its unexpected function. These findings demonstrated that REG3α, previously only considered a biomarker for GVHD, can have a role in saving patients from the disease.

While patients suffering from GVHD are normally given immune suppressants, this research suggested that enhancing the immune system with REG3α is a better strategy and may also be helpful for illnesses such as inflammatory bowel disease that also involve the immune system in the gastrointestinal tract.

"There is a way to treat immune disorders of the gastrointestinal tract by enhancing the immune system rather than suppressing it, as we do now," said lead researcher James Ferrara, MD, Ward-Coleman Chair of Cancer Medicine and Director of the Hematologic Malignancies Translational Research Center at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai and Co-Director of the Mount Sinai Acute GVHD International Consortium (MAGIC). "These results show a new function for the lining of the gastrointestinal tract protecting itself, leading to a new class of drugs."

AUGUSTA, Ga. (Sept. 24, 2018) - The local LGBT community reports twice the number of poor mental health days as the general population of Richmond and Columbia Counties, and those who identified as transgender report twice that, according to a health needs assessment conducted by faculty and students at the Medical College of Georgia at Augusta University.

Area LGBT individuals reported an average of 7.8 poor mental health days, defined as any day they struggled with mental health issues like stress, depression, anxiety and other emotional problems. Those who identified as transgender reported even more days - individuals born female who currently identify as male reported 15.4 days and individuals born male who currently identify as female reported 12.4 days.

The average numbers of poor mental health days on previous assessments of Richmond and Columbia Counties were 3.4 and 2.8, respectively.

"The mental health metrics we measured were the most astonishing in how they differed from the population in general for this area," says Dr. Lara Stepleman, a psychologist in MCG's Department of Psychiatry and Health Behavior.

Around 30 percent of the LGBT sample also reported having suicidal thoughts during their lifetime and 18.5 had actually attempted suicide. Of those who identified as transgender, almost half reported a history of suicidal thoughts and nearly 35 percent had actually attempted.

"In the national data, over and over you find the transgender community fairing far worse," Stepleman says. "There are a lot of reasons - the transgender population as a whole faces much more stigma and can have a harder time finding employment for instance. That type of discrimination leads to other problems like less access to insurance, and therefore access to things they need to gender transition, to live more fully."

The MCG assessment, which is providing the first look at the health needs of the local LGBT community, was taken by 436 people in Augusta and the surrounding area over a five-month period in 2016. The hope is that it will help health care providers better understand the impact of minority stress on other health variables, she says of the assessment results, which are published in the Journal of Homosexuality.

"LGBT people experience the same stressors that anyone else does and when you add their internalized feelings and perceptions of discrimination, there are obvious implications for overall health," Stepleman says. "This assessment is meant to provide an overview, but it helps establish an important baseline and will help us look at the impact of minority stress on a lot of other health variables."

Minority stress describes chronically high levels of stress faced by members of minority groups and can be due to things like poor social support and low socioeconomic status. Many studies have shown that it can contribute to health problems like high blood pressure and anxiety.

The physical health metrics the group measured were less stark, but still concerning, Stepleman says. Asked to number the days they had experienced poor physical health in the last month, the LGBT sample reported 4.5 days. People in Richmond and Columbia Counties previously reported 3.4 and 2.8, respectively.

Around 20 percent of LGBT individuals reported not having health insurance. On the surface, that is not that different from the rest of the community, Stepleman says. "But it is when you consider our sample was largely college-educated, middle-class people. And with the transgender community, even if they do have insurance, many plans still do not fully cover gender transition medications or surgeries."

Other concerns identified by the LGBT assessment included:

A third of the sample reported that they had no
identified or consistent primary care provider.

Almost 50 percent found that their providers needed
more training in LGBT health.

65 percent found community member stigma against
LGBT people a problem - at least a small problem or
higher.

Stepleman and third-year medical student Lauren Wooten Smith spearheaded the design of the survey, which asked 86 questions about various health concerns - both perceived overall wellness and actual disease states they experienced.

Plant sex relies on a combination of prodding and a lot of communication and guidance suggests a study published in the September 2018 issue of Technology.

It's a process that is fraught with challenges. The sperm, two of which are housed in each grain of pollen, are unable to move on their own and the egg cell is deeply embedded in the pistil (the female tissues of the flower). So, to reach the egg the sperm rely on a pollen tube that extends into the pistil. These invasive tubes are the fastest growing cells in the plant kingdom, growing up to 1-2 cm (or 500x their original dimension) an hour, and can sometimes extend up to 30 cm, depending on the anatomy of the flower. To fertilize the egg, the pollen tube (which is between 1/20 and 1/5 of the width of a human hair) has to navigate through a maze of tissue, no matter what obstacles it encounters. The phenomenon is well-documented and known to require communication at cellular level with the female flower tissues, but relatively little is understood about the cell mechanics involved. So scientists from McGill and Concordia collaborated to look more closely at the growth force of individual pollen tubes using a microfluidic lab-on-a-chip.

"From a mechanical point of view, the process of pollen tube elongation is similar to that of a balloon catheter used in angioplasty - forces are generated based on fluid under pressure," explains Muthukumaran Packirisamy from Concordia University's Department of Mechanical and Industrial Engineering. "So, we designed a microscopic cantilever with a gauge built-in that the pollen tubes had to forcefully push against in order to continue to elongate."

Anja Geitmann, formerly at l'Université de Montréal who is now Canada Research Chair in McGill's Department of Plant Science is the senior author on the paper. She adds:

"Thanks to the lab-on-a chip technology we were able to actually see and measure exactly what was going on within the pollen tube as it grew. We discovered that the water pressure and force that these tiny cells exert as they push through the plant tissue to reach their destination is equivalent to the air pressure we put in our car tires to keep them rolling. What is even more exciting is that we found that when the pollen tube encounters an obstacle, it changes its growth pattern, suggesting that the cells are in some ways able to 'feel' and respond to the physical resistance in their environment. It's very exciting to be able to see this process, and it leaves us with a lot of interesting questions ahead about male-female communication."

New avenues are now being opened for future treatment of Laing distal myopathy, a rare disorder that causes muscles in the feet, hands and elsewhere to atrophy. In a study published in the journal PNAS, researchers have identified an enzyme with a clear link to how the disease develops.

"Now we know that the levels of enzyme activity are an important factor in how quickly the disease progresses. This may mean that the disease could be treated by artificially increasing the activity," says Martin Dahl Halvarsson, PhD student in pathology at the Institute of Biomedicine at Sahlgrenska Academy, and the study's first author.

The muscle disease Laing early-onset distal myopathy is caused by an inherited mutation in a muscle protein, myosin, that normally contributes to muscle contraction. The disease often appears at a young age, from age 5 up to about age 20.

What happens with Laing is that muscle fibers, primarily in the legs, hands, hips, neck and shoulders, atrophy over a period of time. With reduced strength and mobility, patients experience impaired quality of life in the long term. How much and how quickly the disease develops varies greatly, however.

In the current study led by Homa Tajsharghi, professor of biomedicine at the University of Skövde, researchers for the first time introduced the mutation for the disease in an entire organism. This was done through mutation of the gene for myosin in fruit flies. The team's previous research has been based on cell culture experiments and experiments outside living organisms.

In this study mutant flies were crossed with fruit flies that had acquired the property of overproducing a particular enzyme. This property is called Abba in fruit flies and MuRF in humans. This sends signals to the cell's proteasome system to destroy the damaged muscle protein.

The researchers then examined several aspects of both the larvae and the adult flies. They studied both how myosin and other proteins organize themselves over a period of time in diseased fruit flies. They also looked at the crawling patterns of the larvae and the adult flies' ability to jump and climb.

The results show that Laing early-onset distal myopathy manifests itself similarly in fruit flies and humans and that the Abba enzyme constitutes a counterbalance to the mutation. Fruit flies with an overproduction of Abba are immune to the disease, provided they are heterozygotes, with one mutated and one normal gene.

The homozygote flies, with double mutations, did not survive to adulthood. In humans, however, homozygotes have never been diagnosed. This might be because people cannot survive with double mutations.

"We have treated diseased fruit flies that carry the same genetic change as patients with Laing distal myopathy," says Homa Tajsharghi, corresponding author behind the study. "The flies were cured and recovered muscle strength and the ability to fly. Naturally there are differences between fruit flies and humans, and additional studies are needed."