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Inhibition of Mitochondrial Calcium Overload by SIRT3 Prevents Obesity- or Age-Related Whitening of Brown Adipose Tissue

The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca2+ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects of capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all of the beneficial effects of capsaicin on alleviating reactive oxygen species generation, elevating mitochondrial activity, and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on the MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of the AMPK/SIRT3 pathway in the maintenance of BAT morphology and function and suggests that intervention in this pathway may be an effective target for preventing obesity- or age-related metabolic diseases.




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Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice

Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcrm–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcrm–/m– mice than in control Hmgcrfl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm–/m– and Hmgcrfl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.




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30 low-key acquisitions who could pay off big

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.




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Cole wins arbitration case vs. Astros

All-Star right-hander Gerrit Cole won his arbitration case against the Astros on Wednesday, meaning he will make $13.5 million this season. The team offerred $11.425 million, a difference of $2,075,000.




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WATCH: Astros' rotation is ready

Spring Training is underway. Players around the league are stepping back onto the baseball field as they get ready for the 2019 season. MLB.com's beat reporters have you covered with the action from every team's training camp. Keep track of the latest highlights of Spring Training right here.




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Back in rotation, McHugh able to draw on relief

With Dallas Keuchel and Charlie Morton leaving in free agency and Lance McCullers Jr. on the mend following Tommy John surgery, Collin McHugh is returning to his roots this year and is back in the Houston rotation. He said his experience as a reliever will only help him evolve as a starter.




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Whitley throws first bullpen session of spring

All eyes were on right-hander Forrest Whitley, MLB Pipeline's top pitching prospect, when he threw in the bullpen for the first time Friday in Major League camp. Astros manager AJ Hinch, assistant general manager Brandon Taubman and director of player development Pete Putila were all watching intently as Whitley threw 21 pitches -- fastballs, changeups and cutters.




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Hall of Famer Biggio visits camp, shares wisdom

The first Hall of Famer to join the Astros at Spring Training is Craig Biggio, who was in uniform for morning workouts on Tuesday and will remain with the team throughout the week.




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UN leader says one billion people with disabilities hard hit by virus

UNITED NATIONS (AP) — The United Nation’s leader said Wednesday the world’s one billion people living with disabilities are among the hardest hit by the coronavirus and called for them to have equal access to prevention and...




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Don’t be too hasty in lifting COVID-19 restrictions – PAHO head

Pan American Health Organization (PAHO) director, Dr Carissa Etienne, is warning that lifting COVID-19 restrictions too soon could accelerate the spread of the virus and open the door for a dramatic upsurge in countries of the region. The warning...




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Rare inflammatory condition affects some children with COVID-19

Dozens of United States children have been hospitalised with a serious inflammatory condition possibly linked with the coronavirus and first seen in Europe. New York authorities announced Wednesday that 64 potential cases had been reported to...




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TV network fights closure with court petition

MANILA (AP): The Philippines’ largest TV and radio network, which was shutdown this week by a government regulator, asked the Supreme Court on Thursday to allow it to return to the air amid an uproar over its closure. ABS-CBN Corp said in its...




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No imminent lockdown restrictions in hard-hit UK

LONDON — Britain’s minister for the environment, food and rural affairs says Prime Minister Boris Johnson won’t be announcing immediate changes to the country’s coronavirus lockdown when he addresses the nation on Sunday....




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US pulls permission for Chinese masks found defective

WASHINGTON (AP) — Federal health officials have revoked US authorisation for masks made by more than 60 Chinese manufacturers after they failed to meet standards needed to protect health care workers. The Food and Drug Administration had...




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Samuda to make strong push for regional pro football league

JAMAICA OLYMPIC Association (JOA) President Christopher Samuda believes that his sports administration experience will aid him in helping to finally shape a professional football league in the Caribbean. Concacaf announced Samuda’s appointment to...




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Umpires suffering ‘dislocation’ but looking to alternatives – Johnson

ROSEAU, Dominica (CMC): A top West Indies Cricket Umpires Association (WICUA) official says regional umpires have also been heavily impacted by the cessation of cricket, stemming from the outbreak of the COVID-19 pandemic. Vivian Johnson, who...




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Ramdin among new Patriots signings

BASSETERRE, St Kitts (CMC): ST KITTS AND Nevis Patriots have made some significant changes to their line-up for the upcoming Caribbean Premier League (CPL) season. Captain Carlos Brathwaite has gone to the Jamaica Tallawahs, while the Patriots have...




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Harriott urges caution with RSPL decision

Portmore United captain Rosario Harriott says the Premier League Clubs Association shouldn’t rush to call off this season of the Red Stripe Premier League (RSPL) because of the COVID-19 pandemic. The league was stopped indefinitely in mid-March...




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Deepening the pool - Western Jamaican swim clubs seek government development and new pool in region to foster training

Western Bureau: A number of swimming officials in western Jamaica say that the region’s struggles with underdevelopment will continue even if the COVID-19 pandemic is brought under control. They say this is because they still lack proper pools to...




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Caymanas Track operations resume tomorrow

Supreme Ventures Racing and Entertainment Limited, operators of Caymanas Track, has announced the re-opening of the main track, effective tomorrow. The company said in a press release on Thursday evening that the track will be opened for two days...




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Former national footballer Lattimore passes

Former national footballer Arthur Lattimore has died. Lattimore, who represented Jamaica in the 1970s, lost his battle with throat cancer at his home in Florida on Thursday. Lattimore, who was known as one of Jamaica's most skilful left-sided...




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Female athletes need more recognition – Clayton

National 400m hurdles champion Rushell Clayton is concerned about what she says are inequalities between men and women in track and field. Clayton was speaking at a Women in Sports Conference in Kingston recently and discussed issues of inequality...




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Men are idiots

Winners of the Darwin Award must eliminate themselves from the gene pool in such an idiotic manner that their action ensures one less idiot will survive. Ben and Dennis Lendrem, and colleagues, have reviewed the data on winners of the Darwin Award over a 20 year period and they join us to discuss why men are idiots, and why their team is not the...




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Is the Hep C screening expansion justified?

Until recently, hepatitis C screening was offered to people at increased risk of infection - such as intravenous drug users - but now, the US Centers for Disease Control and Prevention has recommended screening all people born between 1945 and 1965. Kenny Lin, associate professor of family medicine at Georgetown University in Washington, DC, and...




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International donations to the Ebola virus outbreak: too little, too late?

Karen Grépin, assistant professor of global health policy at New York University, has been examining the pledges made by the international community to help fight the ebola virus outbreak - was it really too little, too late? Read her full analysis: http://www.bmj.com/content/350/bmj.h376




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Obioma Ezekobe GP - patients need to be educated about resources

Obioma Ezekobe is a GP in an urgent care centre in Central Middlesex Hospital. She believes that the public need to be educated about the use of NHS resources, and be taught when it is appropriate to seek care. If you would like to contribute to this collection, please email a brief audio recording to voices@bmj.com or phone +44 (20) 3058 7427...




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They drained 92L from me - diagnosis and management of pleural effusion

Pleural effusions are common, with an estimated 1-1.5 million new cases in the United States and 200 000-250 000 in the United Kingdom each year. Rahul Bhatnagar, academic clinical lecturer at the University of Bristol, describes how pleural effusions may be investigated and treated in the community and secondary care, with a particular focus on...




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What it's like to receive cardiac rehabilitation

With improved survival and and ageing population, the number of people living with coronary heart disease in the UK has increased to an estimated 2.3 million. There is increasing evidence that cardiac rehabilitation benefits these patients, and as such it has been included in international clinical guidelines. ​In this podcast, we're joined by...




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The junior doctor protest

Thousands of NHS staff have demonstrated against the government’s threatened “imposition” of an “unsafe and unfair” contract for junior doctors. At a London rally on Saturday 17 October junior doctors and supporters noisily defended their trade union, as speakers accused England’s health secretary, Jeremy Hunt, of misleading the public about...




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Unexpected findings, with uncertain implications, in research imaging

When healthy volunteers are scanned as part of a research project, unexpected findings, with uncertain implications, can be thrown up. Joanna Wardlaw, professor of applied neuroimaging and honorary consultant neuroradiologist at the University of Edinburgh, joins us to discuss how her group deals with these incidental findings, and what...




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Exercise induced bronchoconstriction

James Smoliga, from High Point University, North Carolina, and Ken Rundell, from The Commonwealth Medical College, Pennsylvania, join us to discuss how to test for, and manage, exercise induced bronchoconstriction, and particularly how to distinguish it from other respiratory conditions. Read the full review at...




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Junior doctors second strike - from the picket line

This week, junior doctors in England have taken industrial action for the second time in as many months after failing to reach agreement with the government over their proposed new contract. Tom Moberley and Abi Rimmer, from BMJ Careers, went to the picket lines at Northwick Park Hospital, and University Hospital Lewisham to talk to the doctors,...




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Should doctors boycott working in Australia’s immigration detention centres?

However well intentioned, working in detention centres amounts to complicity in torture, says David Berger, a district medical officer in emergency medicine at Broome Hospital in Australia. However, Steven Miles, chair in bioethics at the University of Minnesota thinks that they play an important role in telling the world about conditions in...




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"The information we get can be harmfull"; Informed consent is not a panacea

Providing information to enable informed choices about healthcare sounds immediately appealing to most of us. But Minna Johansson, GP trainee and PhD student at the University of Gothenburg, argues that preventive medicine and expanding disease definitions have changed the ethical premises of informed choice and our good intentions may...




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Abortion as a development issue

Interviews from the Women deliver conference in Copenhagen. Catrin Schulte-Hillen, co-ordinator of reproductive health and sexual violence care at Medecins Sans Frontieres, explains why the development community shouldn't conflate sexual violence and access to abortion.




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Likelihood ratios in diagnostic tests

Andrew Elder, a professor at the University of Edinburgh talks about likelihood ratios in diagnostic testing, and how they’re helpful in thinking about how context changes the predictive value of a test. This is part of a wider discussion on the evidence behind clinical examination of the cardiovascular system...




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Not just our ethical credibility as a profession, but our shared humanity

"I say to all Australian doctors - young, old, the political and the apolitical - that on this depends not just our ethical credibility as a profession, but our shared humanity. " Following the leaked emails published in The Guardian newspaper, alleging abuse of asylum seekers detained by the Australian government on the Pacific island of Nauru,...




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Blinding the randomisation

Allocation concealment - blinding which arm of a trial a patient is randomised to - is being questioned in an analysis published on thebmj.com. David Torgerson, director of the York Trials Unit at the university of York and colleagues have been looking at the way in which trials do this randomisation, and how they subsequently report it - and...




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Evidence for vitamin D supplimentation

Despite high quality systematic reviews reporting ineffectiveness, many guideline groups continue to recommend vitamin D supplementation (with or without calcium) for fall or fracture prevention. Recently Public Health England recommended that everyone needs vitamin D equivalent to an average daily intake of 10 μg (400 IU) to protect bone and...




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Education round up - November

The BMJ publishes a variety of education articles, to help doctors improve their practice. Often authors join us in our podcast to give tips on putting their recommendations into practice. In this new monthly audio round-up The BMJ’s clinical editors discuss what they have learned, and how they may alter their practice. In our second audio...




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Education round up - HIV testing, legal highs and care for relatives of the dying

The BMJ publishes a lot of educational articles, and in an attempt to help you with your CPD, we have put together this round-up. Our authors and editors will reflect on the key learning points in the articles we discuss, and explain how they may change their practice in light of that new understanding. In this week's round up we're...




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Fighting inequality, corruption, and conflict - how to improve South Asia's health

The BMJ has published a series of articles, taking an in-depth look at health in South Asia. In this collection, authors from India, Pakistan, Nepal, Bangladesh, Sri Lanka, and Afghanistan collaborate to identify evidence-based solutions to shape health policy and interventions, and drive innovations and research in the region. In this podcast,...




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Drug promotion, prescription, and value

Pharma companies say that money spent on promotion is essential to educate doctors about the best drugs - but when a medical student asked Joseph Ross, associate professor of medicine and public health at Yale, if those companies are promoting the right drugs for that message to be true, the answer wasn't available. Ross and Tyler Greenaway, his...




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The magic of shared decision making

Adoption of shared decision making into routine practice has been remarkably slow, despite 40 years of research and considerable policy support. In 2010, the Health Foundation in the UK commissioned the MAGIC (Making Good Decisions in Collaboration) programme to design, test, and identify the best ways to embed shared decision making into...




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"The interest of diesel drivers over the interest of the public" - tackling air pollution

Air pollution is a truly damaging environmental insult to the human body. The numbers of premature deaths, in the UK alone, that can be attributed to it are calculated to be 40,000 a year. Yet despite this, action to tackle the problem - as with the other huge environmental issue of our time, climate change - is distinctly lacking. Robin...




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Biomarkers - miracle or marketing?

The BMJ has been campaigning for an end to “too much medicine” - the pernicious effect of marketing on the range of tests and treatments that doctors offer patients - tests and treatments which are motivated by the financial reward to the system, than the health of the individual. A new analysis on BMJ.com takes a look at what’s happening in the...




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"For the first time in 15 years the quitting rate has gone up" - ecigarettes smoking cessation

It’s been 10 years since electronic cigarettes hit the shelves in a big way - and since there controversy has reigned about their health effects - are they less unhealthy than smoking traditional tobacco cigarettes, and will they increase nicotine dependence? Its to that last point that new research, published on BMJ.com is looking into -...




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Preventing Overdiagnosis 2017 - Stacy Carter on the culture of overmedicalisation

In this interview from Preventing Overdiagnosis 2017 (preventingoverdiagnosis.net) Stacy Carter, associate professor at Sydney Health Ethics - and the author of a recently written BMJ essay the ethical aspects of overdiagnosis, joins us to talk about how the cultural context of medicine seeps into our decision making processes and affects how...




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HIV in pregnancy - "without the big picture, people aren't going to be able to take the medication"

A new Rapid Recommendation from The BMJ suggests that for pregnant women, they may wish to avoid certain antiviral treatments for HIV. This recommendation differs from the WHO's, and to discuss why that is, and what makes that difference important, we're joined by Reed Siemieniuk, a physician and methodologist from McMaster University, and Alice...




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Diabetes remission - "treating blood glucose, when the disease process is to do with body fat"

In the UK - type 2 diabetes now affects between 5-10% of the population - and accounts for around 10% of our total NHS budget. For the individuals affected, treatments are effective at helping control glucose levels - however, the sequela associated with the disease - vascular problems, and a life expectancy that’s 6 years shorter - are still an...