Synthetic marijuana preferred drug for army users

Synthetic marijuana preferred drug for army users

Social work researchers from the University of Washington have found that among a group of active-duty Army personnel who use illicit drugs, the most abused substance is synthetic marijuana, which is harder to detect than other drugs through standard drug tests.

The research is online and will be published in the July 2014 issue of Addictive Behaviors.

Synthetic marijuana, sometimes called "Spice," is made with shredded plant material coated with chemicals that are designed to mimic THC, the psychoactive compound found naturally in marijuana. The U.S. Drug Enforcement Administration has listed several of synthetic marijuana's main compounds as Schedule 1 substances, making them illegal. But producers of the drug keep synthesizing new compounds to try to get around those bans.

"Because the formulation is constantly changing, one batch could be innocuous while the next batch affects you totally differently and you land in the hospital with seizures," said Tom Walton, project director for the UW study and a research coordinator in social work. "So the health effects are very unpredictable."

Those health effects have not been widely studied yet, but emergency rooms have reported seizures, nausea, vomiting, and cardiovascular and respiratory problems. Psychological effects of using synthetic marijuana can include anxiety, confusion, agitation, irritability, depression and memory issues.

The U.S. military has banned synthetic marijuana in all branches of the service.

Participants in the UW study came from the Department of Defense-funded Warrior Check-Up, a telephone-based intervention trial for Army personnel with untreated substance use issues who are ambivalent about making changes or engaging in treatment. All participants were stationed at Joint Base Lewis-McChord in Washington state at some point during the 2011-2014 recruitment period.

Nearly one-third said they had used illicit substances within the previous 90 days; 38 percent of those used synthetic marijuana, twice as many as had used regular marijuana.

Study participants told researchers they believed that use of synthetic marijuana was significantly higher in the military than in the civilian population. It was the only substance that soldiers believed they used more than civilians, which supports the idea that synthetic marijuana is particularly attractive to military personnel, the researchers said.

"What we think other people do tends to be important in prevention efforts and intervention efforts," said Denise Walker, lead author of the study and a UW research associate professor of social work. "If soldiers think it's common for military personnel to use Spice, then they might think it's OK to use it."

Walker said soldiers tend to avoid treatment for substance abuse issues because seeking treatment automatically goes on their record.

"Who would sign up for that in the civilian population if your boss and your coworkers will immediately know?" Walker said.

The Warrior Check-Up is not considered treatment, and participation is strictly confidential.

Users of synthetic marijuana were younger and less educated than those who were dependent only on alcohol. They were more likely to be single and earned less money than those who were dependent on other drugs or alcohol. But there were no differences in ethnicity, race, deployment history or religion. Researchers also found that synthetic marijuana users were two-and-a-half times more likely to develop drug dependence than those who used other drugs (but not alcohol).

The majority of participants believed their use of synthetic marijuana resulted in failing to meet obligations, such as being late for work, doing their job poorly, or not handling home and child care responsibilities well.

One hazard of using synthetic marijuana was needing more and more to get the same effect, a hallmark of drug dependence. More than three-quarters of users reported using it for much longer than intended (i.e., planning to take just a few puffs after work, but then smoking it for hours).

Walker said there are many reasons why someone would become dependent on alcohol or drugs, but soldiers face added stressors.

"They live very stressful lives. Most of them are young, and they may be going to war or coming back from war," she said. "Being in the Army is very demanding."

The military recently announced that it has developed a urinalysis that can detect synthetic marijuana, but Walton said that test doesn't necessarily have a very high success rate.

"Those drug tests aren't identifying all the users out there," he said. "And, unfortunately, because of the consequences of self-reporting to substance use treatment, positive drug tests are the primary reason soldiers enter treatment. The Warrior Check-Up hopes to change that by helping military personnel change their substance use before it negatively impacts their lives and careers."

Co-authors are Adam Pierce, Lyungai Mbilinyi, Debra Kaysen and Roger Roffman of the UW; and Clayton Neighbors of the University of Houston. The study was funded by the Department of Defense.Department of Defense grant: W81XWH-09-2-0135.

University of Washington

Task Force finds insufficient evidence to recommend for or against screening for suicide risk

Task Force finds insufficient evidence to recommend for or against screening for suicide risk

The U.S. Preventive Services Task Force (USPSTF) finds insufficient evidence to recommend for or against screening adolescents, adults, and the elderly for suicide risk, according to a final recommendation statement being published in Annals of Internal Medicine.

Suicide is the 10th leading overall cause of death in the United States. Past studies estimated that 38 percent of adults (up to 70 percent of older adults) visited their primary care physician within one month of dying by suicide and nearly 90 percent of suicidal youths were seen in primary care during the previous year. As such, researchers for the USPSTF considered whether screening all adolescents, adults, and older adults in the primary care setting for risk factors for suicide would be effective. A systematic review of published research showed that current evidence is insufficient to make a recommendation for or against screening.

However, health care professionals should consider identifying patients with risk factors or those who seem to have high levels of emotional distress and referring them for further evaluation. Some risk factors for suicide include having a mental health disorder, such as depression, schizophrenia, or post-traumatic stress disorder, having a substance abuse issue, or being socially isolated. American Indians or Alaskan natives also have higher rates of suicide. The Task Force continues to recommend that adults and adolescents be screened for depression, as evidence has shown that screening for depression coupled with available treatments is effective. This statement applies to adolescents, adults, and older adults without signs or symptoms of a current mental health disorder or history of mental illness.

Article: Screening for Suicide Risk in Adolescents, Adults, and Older Adults in Primary Care: Recommendations From the U.S. Preventive Services Task Force.

Article adapted by Medical News Today from original press release. Source:

Source: American College of Physicians

Post-traumatic stress disorder: We need more awareness about events that trigger it

Post-traumatic stress disorder: We need more awareness about events that trigger it

Post-Traumatic Stress Disorder (PTSD) is more likely to be recognised in those suffering military combat trauma than in rape and accident victims, according to new research.

Carried out by Dr Ian Tharp, Senior Lecturer in Psychology at the University of Greenwich, the study was led by Chris Merritt, a Greenwich psychology graduate who is currently studying for a Doctorate in Clinical Psychology at King's College London.

During the research, nearly 3,000 participants were shown a description of an individual experiencing identical PTSD symptoms, such as flashbacks, in relation to either military combat, a serious industrial accident or sexual assault, in particular rape.

In comparison to those shown the military scenario, participants were much less likely to recognise the symptoms as PTSD, or even consider them a mental health problem, when associated with either an industrial accident or serious sexual assault.

Dr Tharp says: "The association between PTSD and military combat experience is frequently portrayed in film and television, and the current research supports the pervasive 'traumatised veteran' stereotype.

"However, PTSD can arise from a variety of traumatic experiences, including road traffic accidents, physical or sexual assault, and natural disasters. Across the wider population, these non-military traumas are much more common.

"Furthermore, the likelihood of experiencing and subsequently developing PTSD following these type of events can be much greater than that for military combat."

Dr Tharp concludes: "The implications are that many people who develop PTSD following non-military combat traumas - particularly rape - are less likely to have it recognised by those around them, and are also less likely to seek help for their difficulties."

The study, carried out alongside a third researcher, Professor Adrian Furnham of University College London, was published in the Journal of Affective Disorders.

Chris Merritt adds: "The results show that greater awareness of the key symptoms of trauma is needed within the community in order to identify possible cases of PTSD. This enhanced understanding would also help support services, such as charities, guide individuals towards professional treatments."

A couple's love life may be tainted even 20 years later by early depression, anger

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A couple's love life may be tainted even 20 years later by early depression, anger

A University of Alberta study is helping crack the code to happiness by exploring the long reach of depression and anger over more than two decades.

The study, published recently in the Journal of Family Psychology, followed 341 people for 25 years, and found that negative emotions they may have suffered as young adults can have a lasting grip on their couple relationships, well into middle age.

The fact that depression and anger experienced during the teen years clung to people, even through major life events such as child-rearing, marriages and careers was surprising, said University of Alberta researcher Matthew Johnson.

"We assume or hope that high school experiences fade away and don't necessarily resonate 25 years later. The fact that symptoms of depression and expressions of anger can endure over many large events in life shows how important it is to deal with mental health early. Sometimes, problems don't just dissipate. How you grow and change over those early years becomes crucial to future happiness," said Johnson, an assistant professor of human ecology in the Faculty of Agricultural, Life and Environmental Sciences.

The research, drawn from a larger study begun in 1985, surveyed 178 women and 163 men through their transition to adulthood from age 18 to 25, again on their perceived stress levels at age 32, and on the quality of their intimate relationships at age 43, to find out whether anger or depression they may have felt as young adults was still affecting those bonds.

Findings point to the importance of recognizing that early mental health does influence couple relationships and that in turn, can have social costs later on, such as divorce and domestic violence.

As individuals, people can help themselves by "recognizing the fact that where they are in their couple relationship now is likely shaped by earlier chapters in their lives," Johnson added. "It's not only your partner's current behaviour or your current behaviour shaping your relationship, but the story you bring with you."

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Psilocybin inhibits the processing of negative emotions in the brain

Psilocybin inhibits the processing of negative emotions in the brain

Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role - above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.

Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could "point the way to novel approaches to treatment" comments the lead author Rainer Krähenmann on the results which have now been published in the renowned medical journal Biological Psychiatry.

Psilocybin inhibits the processing of negative emotions in the amygdala

The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann's research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.

Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). "Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions", continues Krähenmann. The study clearly shows that the modulation of amygdalaactivity is directly linked to the experience of heightened mood.

Next study with depressive patients

According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressedpatients - and may consequently lead to improved mood in these patients.

Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers, Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger, Thomas Pokorny, Oliver G. Bosch, Erich Seifritz, Franz X. Vollenweider, Biological Psychiatry, DOI: 10.1016/j.biopsych.2014.04.010, published online 26 April 2014.

University of Zurich

Making amends gives us moral permission to forgive ourselves

Making amends gives us moral permission to forgive ourselves

Research published in The Journal of Positive Psychology claims that it is easier to forgive ourselves for hurting another person if we first make amends, "or give our inner selves a 'moral OK.'"

Psychology researchers, from Baylor University in Waco, TX, report the findings of two studies.

One study involved 269 participants recalling previous offenses - such as romantic betrayals, physical injuries, gossip and rejection - they had committed in their lives. In the other study, 208 people were questioned about a hypothetical offense.

Participants in the first study were quizzed on:

How much they have forgiven themselves for an actual offenseHow much they had tried such efforts as apology, asking forgiveness and restitutionHow much they felt the other person had forgiven themHow much they saw self-forgiveness as morally appropriate.

The people in the study who made the most amends reported feeling the most that self-forgiveness was morally permissible. This process of being able to self-forgive was also made easier if the participants had received forgiveness from the people they had wronged.

The people who made the most amends reported feeling the most that self-forgiveness was morally permissible.

However, there was a broad variation in the types of offense reported by the participants, so the second study was set up by the researchers to further test their hypotheses.

This second study asked the participants about a hypothetical scenario in which they had to imagine failing to take the blame for an action that caused a friend's firing.

This study reported similar results to the first experiment, though one difference was that there was little effect from receiving someone else's forgiveness on whether the participant forgave themselves or not.

Overall, the research showed that the more serious the offense was, and the more guilty the perpetrator felt, the less likely they were to forgive themselves. But making amends could help the wrongdoers reduce their feelings of guilt.

Interestingly, women were also generally found to be less self-forgiving than men. We asked study author Thomas Carpenter, a doctoral student in psychology in Baylor's College of Arts and Sciences, why he thought this was.

"The gender difference is interesting," he replied. "First, I should note that in absolute terms, it is not large. However, a variety of studies have found on-and-off gender differences in self-forgiveness over the years. Because the differences aren't huge, they haven't been the subject of much investigation. It's a great question for future research, though."

Carpenter stresses that the study's main finding is not so much about receiving forgiveness as how our moral attitudes play a part in self-forgiveness.

He told Medical News Today:

"The idea is that the act of trying to do the right thing, almost a sort of penance, helps the situation feel more balanced and gives us moral permission to let go. We hypothesized that people would actually see it as less moral to forgive themselves unless they had sought to make amends first. In other words, we suspected that people actually are withholding self-forgiveness until they have had a chance to at least try to make things right.

Given that moral attitudes toward self-forgiveness were one of the strongest predictors of self-forgiveness across both studies, our research suggests that the process of morally refusing or allowing ourselves to self-forgive is actually quite important in the self-forgiveness process."

Last year, Medical News Today reported on a study by Canadian researchers that suggested the "heaviness" of guilt is more than a metaphor. The researchers published four studies on "embodied cognition" in the journal PLOS ONE, describing how these feelings can be "grounded in subjective bodily sensation," with the sensation of guilt manifesting as a physical heaviness.

Fat-storage gene mutation identified that may increase diabetes risk

Vet-opslag genmutatie geïdentificeerd die diabetesrisico op verhogen kan

Onderzoekers aan de Universiteit van Maryland School van geneeskunde hebben geconstateerd dat een mutatie in een vet-opslag-gen dat lijkt te verhogen het risico voor type 2 diabetes en andere metabole stoornissen, volgens een studie gepubliceerd online in de New England Journal of Medicine.

De onderzoekers ontdekten de mutatie in het hormoon-gevoelige lipase (HSL) gen door het bestuderen van het DNA van meer dan 2.700 mensen in de oude Order Amish gemeenschap in Lancaster County, Pa. HSL is een sleutelenzym die betrokken zijn bij het afbreken van opgeslagen vet (triglyceriden) in vetzuren, waardoor het vrijgeven van energie voor gebruik door andere cellen.

"Wij vonden dat Amish mensen met deze mutatie hebben gebreken in vet opslag, verhoogde vet in de lever, hoge triglyceriden, lage"goede"(HDL) cholesterol, insulineresistentie en verhoogd risico van het ontwikkelen van type 2 diabetes,", zegt senior auteur van de studie, Coleen M. Damcott, Ph.D., een assistent-professor in de geneeskunde in de divisie van Endocrinologie, Diabetes en voeding en lid van het programma voor gepersonaliseerde en genomische geneeskunde aan de Universiteit van Maryland School van geneeskunde.

In deze studie had 5,1 procent van de studiedeelnemers Old Order Amish ten minste één kopie van de mutatie. Vier mensen had twee exemplaren van de mutatie en bijgevolg geen HSL-enzym geproduceerd, zegt Dr Damcott. De mutatie wordt minder vaak in niet - Amish blanken van Europese afkomst (0,2%), dus de hogere prevalentie van de mutatie in de Amish maakt het mogelijk om te karakteriseren zijn volledige scala van effecten.

"Toekomstige studies van dit gen zal ons toelaten om nauwer kijken naar de effecten van de deficiëntie op menselijke stofwisseling om beter te begrijpen de functie van de HSL-eiwitten en het effect ervan op vet en glucose metabolisme," zegt Dr. Damcott. "Deze studies onderzoekt ook de mogelijkheden voor het gebruik van HSL als een drug target voor de behandeling van type 2 diabetes en daarop volgende complicaties."

Ze merkt op dat diabetes type 2 is een complexe aandoening waarvan gevoeligheid wordt vaak bepaald door interacties tussen genetica en lifestyle factoren, zoals overeten en fysieke inactiviteit. Gevoeligheid genen voor diabetes kunnen in meerdere verschillende metabolische routes in het lichaam, met inbegrip van opslag en vrijlating van vet voor energie worden betrokken. "Ontdekking van deze mutatie wordt toegevoegd aan de groeiende lijst van inzichten uit genomic studies die kunnen worden gebruikt voor het ontwikkelen van nieuwe behandelingen en aanpassen van de bestaande behandelingen voor type 2 diabetes en metabole aandoeningen gerelateerd," zegt Dr. Damcott.

Mede-auteur Alan R. Shuldiner, M.D., de John L. Whitehurst begiftigd hoogleraar geneeskunde, associate dean voor gepersonaliseerde geneeskunde en directeur van het programma voor gepersonaliseerde en genomische geneeskunde, en zijn collega's aan de Universiteit van Maryland School van geneeskunde hebben eerder een aantal van gevoeligheid genen voor diabetes evenals wat zwaarlijvigheid, hoge bloeddruk en andere complexe ziekten vastgesteld. In 2008 ontdekten ze een roman genmutatie onder de oude Order Amish bevolking die aanzienlijk vermindert de hoeveelheid triglyceriden in het bloed en wordt weergegeven om te voorkomen dat hart-en vaatziekten. Dr. Shuldiner team heeft het uitvoeren van genetisch onderzoek met de oude Order Amish in Pennsylvania sinds de vroege jaren 1990.

De oude Order Amish zijn ideaal voor genetische studies omdat ze een genetisch homogene bevolking die sporen van hun voorouders terug 14 generaties aan een kleine groep die kwam naar Pennsylvania van Europa in het midden van de jaren 1700s.

Pain receptor regulates lifespan and metabolic health in mice and may have an impact on the man

Pain receptor regulates lifespan and metabolic health in mice and may have an impact on the man

Chronic pain in humans is associated with worse health and a shorter life span, but the molecular mechanisms underlying these clinical observations are not clear. A study published by cell press in the journal cell show that the activity of a pain receptor called TRPV1 longevity and metabolic health in mice. The study suggests that the aging process can affect pain perception and reveals new strategies that could improve metabolic health and longevity in humans.

"The TRPV1 receptor is a great drug target with many well-known drugs in the clinic that can impact function," says senior study author Andrew Deer of the University of California, Berkeley. "Find that manipulation of this receptor can not only to promote a youthful metabolism but also increase service life must be very important for age-related diseases, diabetes is a big problem."

Past research has shown that mice lacking TRPV1 are protected from diet-induced obesity, suggest that this receptor plays a role in the metabolism. Diets rich in capsaicin – the active molecule of chili peppers which can overstimulate and kill TRPV1 neurons-are intriguing, long linked to lower incidents of diabetes and metabolic problems in humans. In addition, distortion of sense perception increases the life span in worms and flies. But so far, it was not known whether sensory perception, also affects aging in mammals.

Addressing this issue in the new study, found that mice Deer and his team genetically manipulated to lack of TRPV1 receptors on average almost four months, or approximately 14%, more than normal mice lived. The TRPV1-deficient mice also showed signs of a youthful metabolism late in life, as a result of low levels of calcitonin gene-related peptide (CGRP)-a molecule that raises the blood glucose levels and thus can contribute to the development of type 2 diabetes. Throughout the aging showed these mice improved glucose tolerance-the ability to quickly clear sugar from the blood, as well as the signs that they can burn more calories without exercising more than usual.

In addition, old mice treated with a substance that the activity of CGRP receptors showed a more youthful metabolic profile than untreated old mice inhibits. "Our findings suggest that pharmacological manipulation of TRPV1 and CGRP can improve metabolic health and longevity," says Deer. "As an alternative, chronic intake of substances that affect TRPV1 like capsaicin can help prevent the decrease in metabolic with age and lead to an increased life expectancy in humans."

Cell, Riera et al.: "TRPV1 pain receptors regulate life span and metabolism by neuropeptide signaling."

Cell press

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Women with diabetes 44 percent more likely to develop coronary heart disease than men with diabetes

Women with diabetes 44 percent more likely to develop coronary heart disease than men with diabetes

A systematic review and meta-analysis of some 850,000 people published in Diabetologia (the journal of the European Association for the Study of Diabetes) shows that women with diabetes are 44% more likely to develop coronary heart disease (CHD) than men with diabetes independent of sex differences in the levels of other major cardiovascular risk factors. The research is by Professor Rachel Huxley, School of Population Health, University of Queensland, Australia; Dr Sanne Peters, University of Cambridge, UK, and University Medical Center Utrecht, the Netherlands, and Professor Mark Woodward, George Institute for Global Health, Sydney, Australia.

The data used in the study stretches back almost 50 years, from 1966 to 2011, and includes 64 studies, 858,507 people and 28,203 incident CHD events, Women with diabetes were almost 3 times more likely to develop CHD (actual relative risk 2.82) compared with women without diabetes, while men with diabetes were only twice as likely (actual relative risk 2.16) to develop CHD than men without diabetes. Combining the two sets of data showed that women with diabetes were 44% more likely to develop CHD than men with diabetes even after consideration was made for sex differences in other CHD factors.

The authors say that this study, the largest ever of its kind backs up findings from a smaller analysis including fewer studies that showed a 46% increased risk of dying from CHD in women with diabetes compared with men with diabetes. In this new analysis by Huxley and colleagues, the sex difference in diabetes-related risk for incident CHD was consistent across subgroups defined by age and region and remained unchanged after excluding non-fatal CHD events. They note that in another previous study they authored, diabetes in women increased the risk of stroke by 25% compared with diabetes in men. They say: "Taken together, these data provide convincing evidence that diabetes poses a greater relative risk for cardiovascular diseases in women than in men."

Several possible reasons for the difference are discussed by the authors. Women have, particularly in the past, been undertreated for risk factors for cardiovascular disease (evident in studies from 1985 and before). However, even in more contemporary populations, when diabetes is treated similar to men, women have generally been less likely to achieve treatment targets. The authors (along with others before them) speculate that women may have to metabolically deteriorate further than men to become diabetic, so they are at a worse starting point even before treatment begins. Furthermore, in the prediabetic state where glucose tolerance may already be impaired but does not meet all diagnostic criteria of diabetes, risk factor levels are more elevated in women than in men. For example, in the UK General Practice Research Database, the BMI of individuals at the time of diabetes diagnosis was, on average, almost two whole units higher (1.8 kg/m2) in women than in men.

The authors say: "It is conceivable, therefore, that the diabetes-related excess risk of CHD in women may be due to a combination of both a greater deterioration in cardiovascular risk factor levels and a chronically elevated cardiovascular risk profile in the prediabetic state, driven by greater levels of adiposity in women compared with men."

They add: "If confirmed, the implementation of sex-specific interventions before diabetes becomes manifest - "such as increased screening for prediabetes, especially in women, combined with more stringent follow-up of women at high risk for diabetes, such as women with a history of gestational diabetes - could have a substantial impact on the prevention of CHD."

Regarding the role of doctors, the authors say: "Physicians may be more likely to recognise the early symptoms of CHD in men than women because of men's higher absolute risk, and thus sex differences in medication use and risk factor control may still exist. Greater awareness of early symptoms of CHD in women and sex-specific therapeutic risk factor management, irrespective of the presence of diabetes, will be the best way to improve clinical outcomes in both women and men."

They conclude: "Women with diabetes have a 44% greater risk of incident CHD compared with men with diabetes. Further studies are warranted to determine the actual mechanisms responsible for the difference in diabetes-related coronary risk between the sexes."

Lifestyle interventions are better than genetic tests for preventing type 2 diabetes

Lifestyle interventions are better than genetic tests for preventing type 2 diabetes

Targeted interventions based on genetic risk may not be the best approach for preventing type 2 diabetes and instead universal strategies to prevent obesity should be prioritized, according to new research published in PLOS Medicine. This analysis, led by Claudia Langenberg from the MRC Epidemiology Unit at the University of Cambridge, UK, suggests that the contribution of genetics to the risk of developing type 2 diabetes is greatest in those who are younger and leaner. However, in this group, the absolute risk of developing type 2 diabetes is low and the number of people who would have to be screened in order to guide targeted prevention would be impractically large.

Diabetes is currently estimated to affect more than 380 million people and the epidemic is likely to increase to 592 million by 2035. Type 2 diabetes is thought to be caused by a combination of genetic and lifestyle factors, such as overweight and physically inactivity. While progress has been made in understanding the genetic basis of type 2 diabetes, the details of how adverse lifestyles combine with genetic risk to determine risk of developing type 2 diabetes are uncertain.

The authors quantified the association of genetic and lifestyle factors with the risk of developing type 2 diabetes in a large cohort of 340,234 people in 8 European countries followed for 11.7 years. In this EPIC-InterAct study, 12,403 people developed type 2 diabetes. The researchers identified an individual's genetic risk by determining how many of a list of 49 known type 2 diabetes genetic variants each study participant carried. They then assessed how this genetic risk contributed to each individual's overall risk of developing type 2 diabetes after several risk factors (such as age, waist circumference, physical activity and Mediterranean diet) were taken into account.

They found that the relative increase in risk of type 2 diabetes for each additional adverse gene carried was greatest in participants who were younger and thinner at baseline. However, risk of developing type 2 diabetes was highest in people who were obese, whatever their level of genetic risk for diabetes. The 10-year cumulative incidence of type 2 diabetes was substantially greater for those with the lowest genetic risk who were overweight (1.29%) or obese (4.22%) compared to normal weight individuals with the highest genetic risk (0.89%).

Professor Nick Wareham, who led the EPIC-InterAct study said "this is the largest study to date examining the impact of genetic susceptibility and lifestyle factors on the risk of developing type 2 diabetes". He added that, "the high absolute risk associated with obesity at any level of genetic risk highlights the importance of population-wide, rather than genetically targeted, approaches to promoting healthy lifestyles that minimise excess weight".

No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; PD: Work was supported by the Wellcome Trust; LCG: Swedish Research Council; MJT: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); LA: EJD: The Spanish Ministry of Health – ISCII RETICC RD06/0020; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; APM: Wellcome Trust grant numbers WT098017 and WT090532; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; SP: Compagnia di San Paolo; JRQ: Asturias Regional Government; OR: The Va¨sterboten County Council; AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; YTvdS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; IB: Wellcome Trust grant 098051 and United Kingdom NIHR Cambridge Biomedical Research Centre; MIM: InterAct, Wellcome Trust (083270/Z/07/Z), MRC (G0601261); ER: Imperial College Biomedical Research Centre.

IB and her spouse own stock in the companies GlaxoSmithKline (GSK) and Incyte (INCY). LCG and MIM are members of the Editorial Board of PLOS Medicine.

Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study, Langenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, et al. PLoS Med, DOI:10.1371/journal.pmed.1001647, published 20 May 2014.

Aspirin delays wound healing: knowledge will impact treatment of chronic wounds

Aspirin delays wound healing: knowledge will impact treatment of chronic wounds

In addition to its known capacity to promote bleeding events, aspirin also inhibits wound healing. New research published in The Journal of Experimental Medicine now describes how aspirin acts on key skin cells called keratinocytes, delaying skin repair at wound sites. A better understanding of this process offers hope for the development of drugs to encourage wounds to heal.

The public health impact of chronic wounds is significant, affecting 6.5 million people in the US alone. Chronic wounds, a common complication of diabetes, are an increasing healthcare burden due to the rising incidence rates for obesity and diabetes. Wound healing is a complex process that is dependent on the restoration of the epithelial layer, the outermost layer of the skin, over the wound surface. Skin cells called keratinocytes play an important role in this process; when keratinocyte migration across the wound is defective, wounds such as diabetic ulcers cannot heal and become chronic wounds. However, we do not fully understand how keratinocyte movement during wound healing is regulated.
Three days after injury, wounds are healing faster in diabetic mice treated with a synthetic form of BLT2 (bottom) compared with untreated mice (top). Arrows mark the length of the wounds, and arrowheads indicate the progress of epithelial restoration.
Credit: Liu et al., 2014

Researchers from Japan were prompted to investigate the role of a molecule called 12-HHT and its receptor BLT2 in wound healing; 12-HHT is produced during blood coagulation following skin injury and BLT2 is found on the surface of keratinocytes. The researchers showed that 12-HHT promotes the re-formation of the epithelial layer at wound sites by enhancing the migration of keratinocytes. They discovered that high dose aspirin, the most commonly used nonsteroidal anti-inflammatory drug, delays wound healing by reducing the production of 12-HHT. The researchers also found that a synthetic mimic of BLT2 accelerated wound healing in diabetic mice (a model that is commonly used to investigate delayed wound healing).

"This study describes a novel mechanism for aspirin's effect in delaying wound healing and suggests that aspirin should be used with caution in patients with chronic wounds," says lead author Takehiko Yokomizo.

Further work will be required to establish whether optimal treatment for wound healing might require a combination of approaches, such as BLT2 agonists together with growth factors to promote the number of wound-healing cells at the wound site, but this study offers hope that it may be possible to develop drugs that promote the healing of chronic wounds in humans.

Height hormone offers target for fighting cancer and diabetes

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Hoogte hormoon biedt doel voor de bestrijding van kanker en diabetes

Een internationaal team - met inbegrip van wetenschappers van de Universiteit van Queensland in Australië - heeft ontdekt dat een hormoon dat bepaalt hoe lang we groeien kan worden gebruikt voor de behandeling van ziekten zoals kanker en diabetes.

Onder leiding van Mike Waters, een professor in het Instituut voor moleculaire bio aan de Universiteit van Queensland, rapporteren de onderzoekers hun bevindingen in het tijdschrift Science.

"Zonder groeihormoonreceptor niet sterven mensen aan kanker of diabetes, waardoor het een ideale drug doel," zegt Prof. Waters.

Echter, gaat hij op om uit te leggen dat we niet genoeg weten over de werking van groeihormoon om ontwerpen te kunnen drugs ter bestrijding van deze ziekten.

Het hormoon werkt door haar receptor - een unieke eiwit op het oppervlak van cellen die een unieke bindt aan een hormoon en in staat stelt om signalen in cellen.

Het team dacht dat als zij meer ontdekken kon over hoe het hormoon met haar receptor samenwerkt - bijvoorbeeld welk deel van het molecuul schakelt de receptor in en uit - dan ze zou kunnen ontdekken een nuttig doel voor het ontwerpen van geneesmiddelen ter bestrijding van ziekten zoals kanker en diabetes.

Deze voorgevoel niet plotseling ontstaan. Prof. Waters is het bestuderen van groeihormoon voor 45 jaar. Hij oorspronkelijk de receptor met toonaangevende wereldwijde biotech Genentech gekloond.

"We hebben nu bedacht hoe groeihormoon op de receptor op moleculair niveau draait," legt hij uit, "en dus hebben een duidelijk idee van welk deel van het molecuul te richten op ontwerp geneesmiddelen om deze ziekten te bestrijden."

Lead Auteur Dr Andrew Brooks zegt dat de impact van hun studie gaat verder dan kanker en diabetes:

"Groeihormoonreceptor is een van een aantal eiwitten bekend als cytokine receptoren, die belangrijke doelstellingen voor therapeutiek voor een scala van aandoeningen, waaronder ontstekingsdarmziekte, bloed stoornissen, osteoporose en obesitas."

Hij zegt dat het een beter begrip van de werking van de groeihormoonreceptor ook aanwijzingen over hoe receptoren voor andere cytokines werken, die moeten helpen drug ontwikkelaars maken van behandelingen voor vele ziekten zal geven.

Onderzoekers zeggen groeihormonen een doelwit voor de bestrijding van vele ziekten, waaronder kanker zou kunnen bieden.

Voor de studie, het team gebruikt een combinatie van kristalstructuren, cel biologie experimenten, biofysische metingen en dynamische modellen van hoe de receptor eigenlijk de informatie die in het hormoon molecuul gebonden stuurt.

De resultaten suggereren dat de receptor blijft in een slapende toestand dat gebaseerd is op twee component moleculen remming van elkaar. Maar wanneer groeihormoon langs komt en aan de receptor bindt, het veroorzaakt een structurele verandering die "wakker" de twee componenten zodat ze elkaar activeren en leiden de cellulaire reactie op het hormoon tot.

Deze wederzijdse inhibitie en activering model kunnen ook de werking van andere soortgelijke cytokine receptoren, concluderen de onderzoekers.

Fondsen van de Australische kanker Research Foundation, de National Health en Medical Research Council en de Australian Research Council hielp de studie financieren.

In januari 2011, medisch nieuws vandaag geleerd hoe een stof die als een "un-groeihormoon fungeert" enkele van de tekenen van veroudering kan keren.

Het onderzoeksteam, waaronder een arts van Saint Louis University, vond dat de compound, bekend als MZ-5-156, die in de tegenovergestelde manier aan groeihormoon optreedt, geremd verschillende menselijke kanker, met inbegrip van kanker van de prostaat, borst, hersenen en longen. De genoemde kan het gebeuren dat de ontdekking contra-intuïtief aan sommige oudere volwassenen die groeihormoon nemen, denken dat het zal hen revitaliseren worden.

Geschreven door Catharine Paddock PhD

New, high-tech device developed for transferring DNA into cells

New, high-tech device developed for transferring DNA into cells

The ability to transfer a gene or DNA sequence from one animal into the genome of another plays a critical role in a wide range of medical research - including cancer, Alzheimer's disease, and diabetes.

But the traditional method of transferring genetic material into a new cell, called "microinjection," has a serious downside. It involves using a small glass pipette to pump a solution containing DNA into the nucleus of an egg cell, but the extra fluid can cause the cell to swell and destroy it - resulting in a 25 to 40 percent cell death rate.

Now, thanks to the work of researchers Brigham Young University, there's a way to avoid cell death when introducing DNA into egg cells. In Review of Scientific Instruments, the team describes its microelectromechanical system (MEMS) nanoinjector, which was designed to inject DNA into mouse zygotes (single-cell embryos consisting of a fertilized egg).

"Essentially, we use electrical forces to attract and repel DNA - allowing injections to occur with a tiny, electrically conductive lance," explained Brian Jensen, associate professor in the Department of Mechanical Engineering at Brigham Young University. "DNA is attracted to the outside of the lance using positive voltage, and then the lance is inserted into a cell."

The MEMS nanoinjector's lance is incredibly small and no extra fluid is used with this technique, so cells undergo much less stress compared to the traditional microinjection process.

This SEM (scanning electron microscope) image shows the nanoinjector next to a latex bead the same size as an egg cell. You can see the size of the nanoinjector and its lance compared to a cell.
Credit: Brian Jensen/BYU

This ability to inject DNA into cells without causing cell death leads to "more efficient injections, which in turn reduces the cost to create a transgenic animal," according to Jensen.

One of the team's most significant findings is that it's possible to use the electrical forces to get DNA into the nucleus of the cell - without having to carefully aim the lance into the pronucleus (the cellular structure containing the cell's DNA). "This may enable future automation of the injections, without requiring manual injection," Jensen says.

It may also mean that injections can be performed in animals with cloudy or opaque embryos. "Such animals, including many interesting larger ones like pigs, would be attractive for a variety of transgenic technologies," said Jensen. "We believe nanoinjection may open new fields of discovery in these animals."

As a next step, Jensen and colleagues are performing injections into cells in a cell culture using an array of lances that can inject hundreds of thousands of cells at once. "We expect the lance array may enable gene therapy using a culture of a patient's own cells," he noted.

The article "A Self-Reconfiguring Metamorphic Nanoinjector for Injection into Mouse Zygotes" by Quentin T. Aten, Brian D. Jensen, Sandra H. Burnett, and Larry L. Howell will be published in the journal Review of Scientific Instruments on Tuesday, May 13, 2014 (DOI: 10.1063/1.4872077).

The paper's first author Quentin Aten participated in this research while at Brigham Young University. He is now working at Nexus Spine LLC.

American Institute of Physics

Adults who lose weight at any age could enjoy improved cardiovascular health

Adults who lose weight at any age could enjoy improved cardiovascular health

Weight loss at any age in adulthood is worthwhile because it could yield long-term heart and vascular benefits, suggests new research published in The Lancet Diabetes & Endocrinology.

The findings are from a study examining the impact of lifelong patterns of weight change on cardiovascular risk factors in a group of British men and women followed since birth in March 1946. They showed that the longer the exposure to excess body fat (adiposity) in adulthood the greater the cardiovascular-related problems in later life, including increased thickness of the carotid artery walls, raised systolic blood pressure, and increased risk of diabetes.

For the first time, the findings also indicate that adults who drop a BMI category - from obese to overweight, or from overweight to normal - at any time during adult life, even if they regain weight, can reduce these cardiovascular manifestations.

The study used data from 1273 men and women from the UK Medical Research Council National Survey of Health and Development (NSHD). Participants were classified as normal weight, overweight, or obese in childhood and at 36, 43, 53, and 60-64 years of age. Cardiovascular phenotyping between the ages of 60 and 64 years with carotid intima media thickness (cIMT; a surrogate marker for cardiovascular events) was used to assess the effect of lifetime exposure to adiposity on cardiovascular risk factors.

According to lead author Professor John Deanfield from University College London (UCL) in the UK, "Our study is unique because it followed individuals for such a long time, more than 60 years, and allowed us to assess the effect of modest, real-life changes in adiposity. Our findings suggest that losing weight at any age can result in long-term cardiovascular health benefits, and support public health strategies and lifestyle modifications that help individuals who are overweight or obese to lose weight at all ages."*

Commenting on the study, Elizabeth Cespedes and Frank Hu from the Harvard School of Public Health, Boston, USA, write, "Although it is encouraging that even transitory weight loss during adulthood has cardiovascular benefits, only 2% of participants in the present study had a sustained reduction in BMI category in adulthood, underscoring the importance of weight maintenance and prevention of weight gain as priorities for public health programming and policy. Improvements in diet and increases in physical activity are crucial levers of long-term weight maintenance and prevention of weight gain in middle-age and early adulthood. Overweight individuals might have even greater health benefit from lifestyle changes such as increased physical activity than do normal weight individuals. The results of this study affirm a continued emphasis on public health policies that enable lifestyle changes to achieve and, especially, to maintain a healthy BMI."

They add that, "Ideally, future research will address long-term patterns of intentional versus unintentional weight loss, the means to achieve weight loss, and the weight loss maintenance necessary to reduce cardiovascular endpoints."

"Battle of the bulge" may be linked to body clock in immune cells

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"Battle of the bulge" may be ?linked to body clock in immune cells

It's all in the timing, according to Texas A&M researchers who have confirmed disruption of the internal biological clock plays a key role in the development of metabolic diseases, including obesity and diabetes. Their study, published in the Journal of Biological Chemistry, suggests a high-fat diet alters the timing of our body clock, particularly in immune cells that are involved in mediating inflammation in obesity. ?

Our "body clock" is located in virtually all cells and controls circadian rhythms, 24-hour cycles that tell our bodies when to sleep and regulate many physiological processes, including inflammation and metabolism. When our circadian rhythms are disrupted, sleeping patterns and metabolism become unbalanced, notes study authors David Earnest, Ph.D., professor at the Texas A&M Health Science Center College of Medicine's Department of Neuroscience and Experimental Therapeutics and Chaodong Wu, Ph.D., associate professor in the Department of Nutrition and Food Sciences at the Texas A&M College of Agriculture and Life Sciences. With combined interests in sleep cycles and nutrition, the duo has jointly explored effects of unhealthy eating on circadian rhythms for a number of years. ?

"Under normal conditions, circadian clocks help maintain the anti-inflammatory function of immune cells and keep metabolism functioning properly," said Earnest. "With a high-fat diet, the circadian clock is dysregulated, which intensifies inflammation and fat deposition and leads to systemic insulin resistance and glucose intolerance."? Earnest notes the internal body clock is akin to a watch. When you have a watch with a weak battery, your watch "loses time," as do you. You will think it's 3 p.m., when, because the watch is now running slow, it's actually 9 p.m. Saturated fatty acids have the same effect as weak watch batteries, making our clocks run long.?

Using an animal model, the team tested the effects of over-nutrition on body clocks. The test group was fed a high-fat diet and controls were fed a low-fat diet. The study found that a high-fat diet increased the normal functioning body clock from a 24-hour cycle to a 30-33 hour cycle, particularly in immune cells involved in mediating inflammation. This, in turn, results in six to nine hours of time lost each day, causing critical inflammatory and metabolic processes to occur at abnormal times throughout the day.

"As key components of inflammation in obesity, immune cells contain circadian clocks that regulate daily rhythms in inflammatory responses," Earnest said. "Our experiment was able to demonstrate that a high-fat diet alters the molecular 'gears' of the clock along with the inflammatory responses in these immune cells, which can lead to metabolic disorders."? The team also conducted novel "bone marrow transplantation" experiments to allow circadian clock disruption only in immune cells used to "re-populate" immuno-deficient recipients.?

"The mere 'breakdown' of circadian clocks in these immune cells increased adipose and liver tissue inflammation, fat deposition and systemic metabolic dysfunction caused by a high-fat diet," Wu said.

Independent data from the researchers suggests that "bad" saturated fatty acids (common in high-fat diets) perturb circadian clocks at specific times of the day/night when their pro-inflammatory effects are maximal. With these findings, Earnest is working on a complementary study to show that specific polyunsaturated "good" fatty acids or drugs that target inflammatory pathways could prevent the effects of saturated fatty acids, in both dysregulating the clock and increasing pro-inflammatory responses. ?

Findings could ultimately lead to therapeutic strategies for treating obesity-related metabolic disorders, especially the progression of insulin resistance in type 2 diabetes and other inflammation-related health disorders such as cardiovascular disease, stroke, arthritis and even recovery from injury-induced inflammation, common in sports injuries. ?

"Keeping our body clock running properly is vital," Earnest said. "To promote health, we need to eat healthy foods, and more importantly keep a healthy lifestyle, which includes avoiding sleeping late and eating at night. Time your body right and it will work better."??

Myeloid cell-specific Disruption of Period1 and Period2 Exacerbates Diet-induced Inflammation and Insulin Resistance, Hang Xu, Honggui L, Shih-Lung Woo, Sam-Moon Kim, Vikram R. Shende, Nichole Neuendorff, Xin Guo, Ting Guo, Ting Qi, Ya Pei, Yan Zhao, Xiang Hu, Jiajia Zhao, Lili Chen, Lulu Chen, Jun-Yuan Ji, Robert C. Alaniz, David J. Earnest and Chaodong Wu, Journal of Biological Chemistry, DOI: 10.1074/jbc.M113.539601, published 25 April 2014.

Texas A&M Health Science Center

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Physical activity could stop gestational diabetes progressing to type 2

Physical activity could stop gestational diabetes progressing to type 2

A new study published in JAMA Internal Medicine finds that increased physical activity can lower the risk of gestational diabetes mellitus progressing to type 2 diabetes mellitus.

A common complication of pregnancy, gestational diabetes mellitus (GDM) is defined as glucose intolerance that occurs or is first recognized during pregnancy. About one third of women of reproductive age with type 2 diabetes mellitus (T2DM) have a history of GDM.

T2DM is now defined as an escalating worldwide epidemic, so diagnosing GDM is important in that it allows women to recognize the risk of T2DM and to take action to try and prevent it.

In order to take action that might prevent GDM from progressing to T2DM, though, it is necessary for research to identify what risk factors in this high-risk population are modifiable. The researchers behind the new study had established in previous work that a healthful diet is associated with a lower risk of T2DM in women with a history of GDM.

Glycemic control may be regulated by physical activity, which also facilitates weight loss and weight maintenance, so the researchers wondered if regular physical activity could prevent or delay the onset of T2DM.

Using data from the Nurses' Health Study II, the study looked at 4,554 women with a history of GDM who were followed between 1991-2007. The study captured information on the women's physical activity and sedentary activity, such as watching TV. Within this group, 635 of the women went on to get T2DM.

The researchers calculated that every increase in increments of 100 minutes per week of moderate-intensity physical activity (or 50 minutes per week of of vigorous-intensity activity) was associated with a 9% lower risk of T2DM.

Women who increased their physical activity by the federal government recommendation of 150 minutes per week of moderate-intensity physical activity (or 75 minutes per week of vigorous-intensity activity) were found to have a 47% lower risk of T2DM.

However, the researchers also found that an increase in the amount of time watching TV was associated with a greater risk of T2DM. The researchers stress, though, that T2DM risk is not raised by TV watching per se, but that an unhealthy lifestyle highly correlated with TV watching could influence risk.

Women who increased their physical activity by the federal government recommendation of 150 minutes per week of moderate-intensity physical activity (or 75 minutes per week of vigorous-intensity activity) had a 47% lower risk of T2DM.

"For example," the authors write, "TV watching typically acts as a sedentary replacement for physical activity leading to a reduction in energy expenditure, and TV watching is associated with 'mindless' eating, increasing food and total energy intake. Finally, while watching TV, women may be influenced by commercial food advertisements for nutrient-poor, high-calorie foods."

This study included a large sample of participants who were studied over a long period of time.

However, as the participants were all nurses, it is possible that the results could be confounded by the nurses being more health conscious or by having different access to health care than the general population.

Also, the participants were mostly white American women, so it may not be possible to generalize the results to other groups.

The authors conclude their study by writing:

"Our results from a large prospective study indicate that increasing physical activity may help lower the risk of progression from GDM to T2DM. These findings suggest a hopeful message to women with a history of GDM, although they are at exceptionally high risk for T2DM, promoting an active lifestyle may lower the risk."

Last November, Medical NewsToday reported on new guidelines for diagnosing gestational diabetes.

Written by David McNamee