It is definitely a make-or-break season for those trying to balance career and COVID-19 at home. For some, it is the ideal time to reconnect with themselves, family members and get creative with work. While with others, the cookie crumbles and they...

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.

As the Mets, Nationals and Phillies have made multiple upgrades, Braves GM Alex Anthopoulos has thus far limited his offseason activity to giving Josh Donaldson a record one-year deal and bringing to fruition the desires of Brian McCann and Nick Markakis to play for the Braves.

Reporter Mark Bowman addresses the Braves' offseason as a whole, as well as identifying a Minor League who has a chance at making the club out of Spring Training.

In outlining their plans to rebuild the Orioles following the least successful season in franchise history, new club officials routinely point to experience: They just did the same thing elsewhere.

The Orioles' cloudy infield picture gained some clarity Saturday when the team signed veteran shortstop Alcides Escobar to a Minor League contract with an invitation to Spring Training.

The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals’ susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual’s capacity to oxidize dietary fat is a metabolic determinant of weight change.

OTTAWA, Canada (CMC): The Confederation of North, Central American and Caribbean Association Football’s (Concacaf) hexagonal round of qualifying for the 2022 FIFA World Cup in Qatar may have to be scrapped because of the disruption the COVID-19...

Jamaica Football Federation (JFF) general secretary Dalton Wint says that any potential changes to the Concacaf hexagonal round for the FIFA World Cup qualifiers could present challenges to the nation’s aim of qualifying for Qatar 2022. Wint’s...

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...

Philipe de Souto Barreto argues that, to reduce premature mortality, policies should focus on getting fully inactive people to do a little physical activity rather than strive for the entire population to meet current physical activity recommendations. Read the full analysis paper: http://www.bmj.com/content/350/bmj.h23

Following on from the clinical review "Caring for sex workers", we spoke to the team at Open Doors, a sex worker outreach clinic in east London, run from the Homerton University Hospital NHS Foundation Trust. Kim Leveret and Anca Doczi join us to give practical advice on reaching out to sex workers, what barriers exist to them accessing care, and...

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...

The UK Parliament's Health Select Committee's recent report on childhood obesity says 1 in 5 children are obese by the time they leave school. The committee calls for legislation to turn the tide by taxing sugary drinks, a pre-watershed ban on junk food advertising, and investment in public health. We joined Sarah Wollaston, conservative MP for...

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...

The BMJ recently held a discussion between experts in the fields of general practice, emergency medicine, and paediatrics about the state of out of hours care in the UK, and crucially offered their vision for a better service. Are children a special case, can urgent care ‘hubs’ be a silver bullet, is NHS 111 up to the job of triaging patients,...

We do we know about the weekend effect? As Martin McKee puts it in an editorial on thebmj.com, "almost nothing is clear in this tangled tale" In this roundtable, Navjoyt Ladher, Analysis editor for The BMJ is joined by some of the key academics who have published research and commented on the weekend effect to make sense of what we know and...

With the emergence of sofobuvir, a new direct acting antiviral, treatment for Hepatitis C infection is currently undergoing it's greatest change since the discovery of the virus 25 years ago. However Gilead, who manufacture the treatment, are under fire for the cost of the druge - around $90 000 for a course of treatment. Victor Roy, doctoral...

Glasgow GP, writer, broadcaster, and The BMJ's weekly columnist Margaret McCartney joins us to talk about her new book "The State of Medicine: Keeping the Promise of the NHS". Read all of Margaret's columns: goo.gl/iKmmie

Persistent physical symptoms are common and include those symptoms that last at least three months and are insufficiently explained by a medical condition after adequate examination and investigation. Observational studies in primary care report that women, especially those aged 35-45 years, more commonly present with these symptoms. In this...

For seven years, Republicans have vowed to repeal the Affordable Healthcare Act (Obamacare), and that promise took a central place in President Trump's campaign. The first major vote to replace it was due to happen last week, but was cancelled at the 11th hour. In advance of the potential vote, The BMJ published a debate asking "Should US doctors...

It’s been called “the universal panacea” - exercise has a positive effect on almost all health measures, and governments are actively campaigning for us to do more. But at the opposite end of the scale, the realisation that some people may be addicted to exercise is gaining traction. In this podcast we're joined by Heather Hausenblas - professor...

Each individual’s grief process is unique, when confronted with the death of a loved one, most people experience transient rather than persistent distress - however 10% of bereaved individuals, with an increased risk following the death of a partner or child and loss to unnatural or violent circumstances, experience prolonged grief disorder. In...

"Too many research studies are poorly designed or executed. Too much of the resulting research evidence is withheld or disseminated piecemeal. As the volume of clinical research activity has grown the quality of evidence has often worsened, which has compromised the ability of all health professionals to provide affordable, effective, high value...

The increase in life expectancy in England has almost “ground to a halt” since 2010 and austerity measures are likely to be a significant contributor. In this podcast Michael Marmot, director at University College London’s Institute of Health Equity, joins us to discuss what might be causing that drop off, and why a decrease in early life chances...

There's a crisis in old age care - not just in the UK, around the world, as population demographics shift, and the proportion of older people increase - there's a worry about who's going to look after them, and how much is it going to cost? However, a new analysis on bmj.com says this picture need not be so gloomy - they say that encouraging...

Assessing young people with possible eating disorders can be complex for a variety of reasons. Building a therapeutic relationship with a young person with a possible eating disorder and their family is key to enabling a thorough assessment and ongoing management, but it introduces difficult issues regarding confidentiality and risk. In this...

As the accompanying editorial to this article says, "oxygen has long been a friend of the medical profession Even old friendships require reappraisal in the light of new information." And that’s what a new rapid reccomendation - Oxygen therapy for acutely ill medical patients - does. To discuss we're joined by two of the authors, Reed Simieniuk,...

Welcome to this, trial run, of a new kind of BMJ podcast - here we’re going to be focusing on all things EBM. Duncan Jarvies, Helen Macdonald and Carl Heneghan - and occasional guests- will be back every month to discuss what's been happening in the world of evidence. We'll bring you our Verdict on what you should start or stop doing, geek out...

On the 7th of June, 1753, Dr Archibald Cameron was executed at Tyburn. "The body, after hanging twenty minutes, was cut down: it was not quartered; but the heart was taken out and burnt. " 250 years later, his sixth great grandson, Robert Syned found himself deeply involved in the process of execution, as an expert witness in a case about the use...

Helen Macdonald and Carl Heneghan are back again talking about what's happened in the world of evidence this month. (1.20) Carl grinds his gears over general health checks, with an update in the Cochrane Library. (9.15) Helen is surprised by new research which looks at over prescription of antibiotics - but this time because the courses...

Starting in the middle of April, the group “Extinction Rebellion” have organised a series of non-violent direct action protests. Most notably bringing central London to a standstill - but these events are now continuing around the country. Predictably, they have received a lot of criticism - they have also received a lot of support - amongst...

The National Surveys of Sexual Attitudes and Lifestyles is a deep look into the sex lives of us brits - and has been running now for 30 years, giving us some longitudinal data about the way in which those sex lives have changed. The latest paper to be published, based on that data, looks at the frequency of sex - how often different groups are...

Welcome back to Talk Evidence - where Helen Macdonald and Carl Heneghan take you through what's happening in the world of Evidence. This month we'll be discussing tramadol being prescripted postoperatively, and a new EBM verdict says that should change(1.36). How much preventable harm does healthcare causes (11.20. A canadian project to help...

Brexit. Who knows what’s going to happen in the next few weeks, months, years - the uncertainty is high. In the face of that, you’d hope that the government was doing all it could to plan for any eventuality - let alone for a massive, country altering one like suddenly crashing out without a deal - but Martin McKee, professor of public health at...

In the UK, for just over a year, we've been paying the "Soft Drinks Industry Levy" - a tax on sugary beverages intended to reduce our consumption of free sugars. That was based on taxes that had happened in other countries, however, in the UK high sugar snacks, such as confectionery, cakes, and biscuits make a greater contribution to intakes of...

This week we saw the release of the much awaited Yellowhammer documents from the government, documents which outline some of the risks involved with Britain’s sudden departure from the EU. The documents themselves outline that there are risks to the supply of medicines - but do not set out the detail of how those risks have been mitigated, and...

Our latest series kicks off with Australia’s multi-award-winning health and science reporter, Liam Mannix. He joins Ray to share his insights into the role and impact of evidence, advocacy and investigative reporting in today’s ever-changing media landscape.

As editors, we feel like we’re spending a lot of time taking the superlatives out from articles - amazing, novel, important… But new research on BMJ.com suggests that we might not be doing that great a job, and that for some reason, papers authored by men tend to have more of them - because men put more in, or maybe a bias against woman writing in...

Welcome to the festive talk evidence, giving you a little EBM to take you into the new year. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford University’s CEBM and editor of BMJ Evidence) This month: (2.00) Helen look back at a Christmas article, which...

In this week's special episode of Sharp Scratch, we've got something a little different for you! Last week the panel talked microaggressions, so this week we're hearing from an expert guest who is leading the work the NHS is doing to combat inequality in healthcare. If you like this special edition, let us know on Facebook, Instagram or Twitter...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications

Steven M Haffner
Jun 1, 1992; 41:715-722
Original Article

DE Kelley
May 1, 2000; 49:677-683
Articles

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article

D Dabelea
Dec 1, 2000; 49:2208-2211
Articles

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles