Public reaction to the initial threat of the coronavirus (COVID-19) was predictably mixed. While international news of the contagion across continents helped people to appreciate that this was not restricted to a particular region, not many people...

On Tuesday, April 14, the International Monetary Fund downgraded Jamaica’s growth prospects to -5.6 per cent. This is a severe contraction warranting substantial Government intervention. However, at times, the Government waits too late to respond...

Novelist, writer and designer Edith Wharton once said, “There are two ways of spreading light – to be the candle or the mirror that reflects it”. Shining a light of faith and hope for girls through the provision of an open and safe place is Britney...

Let’s face it, ladies: boosting your health is not always your primary priority, but it needs to be. It doesn’t require a long, overbearing and spine-chilling regime. Simple lifestyle changes can get the job done! In the end you’ll be left with a...

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...

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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.

Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and mouse pancreas over a range of ages and states of diabetes. Very few LDs were found in normal human juvenile pancreatic acinar and islet cells, with numbers subsequently increasing throughout adulthood. While accumulation appeared evenly distributed in postjuvenile acinar and islet cells in donors without diabetes, LDs were enriched in islet α- and β-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell–derived β-cell clusters. In contrast, LD accumulation was nearly undetectable in the adult rodent pancreas, even in hyperglycemic and hyperlipidemic models or 1.5-year-old mice. Taken together, there appear to be significant differences in pancreas islet cell lipid handling between species, and the human juvenile and adult cell populations. Moreover, our results suggest that LD enrichment could be impactful to T2D islet cell function.

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells and very few INS⁺ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.

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.

As Braves manager Brian Snitker evaluates who might serve as his closer, A.J. Minter has made it clear he wants to be the guy who is consistently called upon to handle high-leverage threats that develop in late innings.

Frank Robinson, a trailblazing figure who was Major League Baseball's first African-American manager and one of its greatest players during a career that spanned 21 seasons, died Thursday after a prolonged illness. He was 83.

The Orioles' restocked farm system might inject some excitement into the club's retooled roster.

Wave him bye bye. A legendary voice of Orioles baseball is calling it a career. Joe Angel, beloved play-by-plan man and voice of the Orioles' radio broadcasts for nearly two decades, announced his retirement this week. The decision caps a 41-year career in the booth for Angel, 71, a fixture for 19 seasons across two stints in Baltimore.

Pitch clocks are set to make their Spring Training debuts this week, and it will be in games featuring hordes of players for whom playing on a timer is nothing new.

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.

By winning his arbitration case against the Astros, pitcher Gerrit Cole stands to make $2,075,000 more this season than if he'd lost. That's a significant victory for Cole, who will double his salary this year and make $13.5 million, and a significant victory for other players to come, the veteran pitcher said.

Astros third baseman Alex Bregman continues to progress from the arthroscopic elbow surgery he had a month to remove bone chips.

The first live bullpen sessions of the spring typically draw a crowd, and that certainly was the case when Justin Verlander, Gerrit Cole and Brady Rodgers faced hitters for the first time Sunday afternoon on the back fields at Ballpark of the Palm Beaches.

JERUSALEM (AP): Israeli Prime Minister Benjamin Netanyahu formally received the support of a majority of lawmakers to lead a new government yesterday, paving the way for a controversial power-sharing deal with rival-turned-partner Benny Gantz....

Germany’s decision that football can return this month provided encouragement for players and teams across Europe yesterday that the shutdown caused by the coronavirus pandemic could soon be coming to an end. With COVID-19 infections declining,...

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...

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...

Bone pain is the most common type of pain from cancer and is present in around one third of patients with bone metastases, currently, improvements in cancer treatments mean that many patients are living with metastatic cancer for several years. Christopher Kane, NIHR academic clinical fellow in palliative medicine at Leeds University School of...

Participants in our discussion on person centred care in January agreed that a change in culture and better use of technology could benefit both patients and doctors. At the roundtable: Fiona Godlee (chair), editor in chief, The BMJ Tessa Richards, senior editor, patient partnership, The BMJ Rosamund Snow, patient editor, The BMJ Navjoyt Ladher,...

Michelle Sinclar, a GP in Hampshire who is concerned that GP premises aren't fit for purpose and limit her ability to provide fully rounded patient care. BMJ Voices is a collection of readers’ experiences of working in the NHS. For this, The BMJ is seeking short audio submissions from UK listeners. These submissions will be published on...

Cervical screening programmes in many countries stop at around the age of 65 and much of the focus is often on younger women. However, comparatively little attention has been given to older women despite the fact that they account for about a fifth of cases each year and half of deaths. In this podcast Susan Sherman, a senior lecturer in...

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...

In the podcast, we’ll hear from Kevin Hines the survivor of such an attempt, and Alys Cole-King, a psychiatrist who wants to break down the stigma of suicide. Originally broadcast in 2010 For more on suicide risk assessment and prevention, read our latest clinical review: http://www.bmj.com/content/351/bmj.h4978

Nick Oliver, consultant diabetologist at Imperial Healthcare NHS Trust and Philippa Cooper, who has type I diabetes, join us to explain how structured education works for patients, and give tips on self management. Read the full review: http://www.bmj.com/content/352/bmj.i998

In February World Health Organization (WHO) declared the microcephaly epidemic in South America an international public health emergency. Today, the US Centers for Disease Control and Prevention, the CDC, has confirmed that it’s is Zika virus which is causing that microcephaly.  The outbreak was originally spotted in Recife, in Brazil, and it’s...

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...

When a person’s heart or breathing stops and the cause is reversible, immediate cardiopulmonary resuscitation (CPR) offers a chance of life. However, when a person is dying—for example, from organ failure, frailty, or advanced cancer—and his or her heart stops as a final part of a dying process, CPR will not prevent death and may do harm. But...

Our latest debate asks whether there should be a Royal Commission (a high level enquiry, with statutory powers) into the future of the NHS. A high level inquiry could detoxify the radical changes needed and command wide support, say Maurice Saatchi, conservative peer, and Paul Buchanan, The BMJ's patient editor; but Nigel Crisp, independent peer,...

If you google "The NHS" you'll see screaming headlines from the Daily Mail about cost and waste - debate in parliament is about how much of our GDP we should be spending - and each year, hospital trusts go cap in hand to ask for more funding. Against this backdrop, a new analysis, and a first in a series, published on bmj.com, looks at what it...

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...

Ravi Gupta, is a resident in internal medicine at Johns Hopkins in Baltimore - and as he said has seen the influence of sudden price hikes on his patients - between 2010 and 2015 more than 300 drugs in the U.S. have seen sudden increases of over %100. Ravi and his co-authors have suggested, and tested the feasibility of, a possible answer to...

The first digital banking in the UK was launched in 1983, Skype turns 15 this year, but 2017 finally saw panic over the impact that online consultations may have on general practices. In this podcast Martin Marshall, professor of healthcare improvement at University College London joins us to discuss whether video conference actually is a...

In 2016, from an estimated pre-war population of 22 million, the United Nations (UN) identified 13.5 million Syrians requiring humanitarian assistance, of which more than 6 million are internally displaced within Syria, and around 5 million are refugees outside of Syria. In this podcast, Aula Abarra, consultant in infectious disease from London,...

At evidence live this year, one of the sessions was about the work of Evidence Aid - and their attempt to bring high quality evidence to the frontline of a humanitarian crisis. In that situation, it’s very difficult to know what will work - a conflict, or even immediately post-conflict situation is characterised by chaos - and merely doing...

Doctors and the farming industry are often blamed for overuse of antibiotics that spurs the growing problem of antimicrobial resistance - but the professions are using different methods to combat resistance and reduce overuse. In this roundtable, we bring medics and vets together to discuss the problem - where antibiotic resistance arises, how...

Mendelian randomisation - it’s a technique that uses the chance distribution of genes in a population, combined with big data sets, to investigate causative relationships. But there are a lot of questions we have in The BMJ about how the technique works - the association between genes and apparently non-biologically mediated behaviours, how much...

More than ½ of patients leave hospital with changes to four or more of their long-term medications - but how appropriate are those changes? New research published on bmj.com looks at antihypertensive medication prescription changes to try and model that - and found that more than half of intensifications occurred in patients with previously well...

Cardiovascular factors are associated with risk of stroke - and those factors can be mediated by lifestyle and by genetic make up. New research published by The BMJ sets out to explore how these risks combine, and we're joined on the podcast by two of the authors - Loes Rutten-Jacobs, senior postdoctoral researcher at the German Center for...

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...

You’ll have read in a clinical trial “Most patients had an acceptable adverse-event profile.” Or that a drug “has a manageable and mostly reversible safety profile.” And that “the tolerability was good overall.” In this podcast, Bishal Gyawali (@oncology_bg) joins us to describe what events those terms were actually describing in cancer drug...

Diabetes is synonymous with sugar, but diabetes insipidus, "water diabetes", can't be forgotten. Between 2009 and 2016, 4 people died in hospital in England, when lifesaving treatment for the condition was not given. In this podcast, we hear some practical tips for non-specialists to aid diagnosis, and how patients should be managed during...

In every generation there are a few that know the secret; the counterintuitive effects of loop diuretics. In this podcast Steven Anisman, cardiologist at the Dartmouth Hitchcock Department of Cardiovascular Medicine, joins us to explain about the threshold effects of these drugs, and why that might change the way in which you think about...