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.

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

Here are answers to some of the primary questions you may have as the defending National League East champs prepare to begin Spring Training next week.

Freddie Freeman spent the offseason sharing excitement about the possibility that Josh Donaldson would not end up being the Braves' only significant offseason addition.

Braves manager Brian Snitker joked that he could almost detect a smile as he shared a phone conversation with Nick Markakis after the stoic outfielder re-signed with the club in January. Snitker and others actually saw that smile on Tuesday morning, when Markakis reported to Spring Training to begin his fifth season with the Braves and attempt to push the club past the rebuild he positively enriched through his leadership.

Sean Newcomb entered last June as an All-Star candidate and exited the regular season wondering if he had done enough to earn a spot on Atlanta's postseason roster. The inconsistent nature of his first full Major League season enhances the difficulty of projecting how valuable he might be to the Braves from both an immediate and long-term perspective.

The Orioles' crowded outfield mix gained another member on Monday when the team signed veteran Eric Young Jr. to a Minor League contract with an invitation to Spring Training.

Since the Rays debuted "the opener" last May, no fewer than eight teams have helped transform the concept from a fad into a mini-movement. Consider the Orioles a candidate to dive in next.

For Brandon Hyde, the days and weeks leading up to Tuesday were filled with phone calls to friends, to former colleagues, to mentors he's made across more than two decades in the game. A constant theme emerged from the ensuing chats: What, exactly, should Hyde expect from his first Spring Training as a big league manager?

It may take the Orioles a little longer than expected to sift through their crowded catching situation. A club source confirmed that catcher Jesus Sucre is held up by visa issues in his native Venezuela and will report to camp late.

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 (Hmgcr^m–/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 Hmgcr^m–/m– mice than in control Hmgcr^fl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcr^m–/m– and Hmgcr^fl/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.

Gerrit Cole and Justin Verlander are not fans of the "opener" and explained why it's not a long-term option.

The question would come shortly after Cy Sneed would write his name on the chalkboard. A young hand would rise into the air, and Sneed would brace himself for the chuckles that were sure to soon fill the classroom. "Are you a lumberjack?"

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...

Airbnb says it is laying off 25% of its workforce as it confronts a steep decline in global travel due to the new coronavirus pandemic. It’s a serious setback for the 12-year-old home-sharing company, which just a few months ago was...

COVID-19-ravaged regional economies, including Jamaica, will need the united strength of the Caribbean Single Market and Economy (CSME) to help revive their micro, small and medium enterprise (MSME) sectors, many of which have been decimated. That...

JOHANNESBURG (AP) — A virtual meeting of South African lawmakers has been disrupted by hackers who flooded the video call with pornographic images. In the incident on Thursday, the hackers also hurled racial and sexual insults at the meeting...

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...

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...

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...

BERLIN, Germany (AP): THE BUNDESLIGA football season will resume on May 16 in empty stadiums, picking up right where it left off two months ago amid the coronavirus pandemic. Yesterday’s announcement comes one day after clubs were told the season...

KINGSTON COLLEGE (KC) principal Dave Myrie has refuted claims that St Jago High School sprint hurdler Vashaun Vascianna will be joining the school this September. The Gleaner understands that Vascianna, who broke the Class Two boys’ 110m hurdles...

MADRID, Spain (AP): Rafael Nadal says Novak Djokovic will need to be vaccinated to keep playing if the governing bodies of tennis make coronavirus shots obligatory once they become available. Nadal told the Spanish newspaper La Voz de Galicia this...

Former national footballer Arthur Lattimore passed away after a long battle with throat cancer. Lattimore, who represented Jamaica’s football team through­out the 1970s, died at his home in Florida, leaving behind five children, grandchildren, and...

The UK’s austerity programme has disproportionately affected children and people with disabilities, says David Taylor-Robinson, a senior clinical lecturer in public health at the University of Liverpool. He joins us to discuss why the evidence shows the vulnerable are hit hardest by the cuts to public services, despite the UN conventions on...

Jackie Applebee is a GP in Tower Hamlets in London, and is concerned that the way the GP funding formula is working doesn't take account of the earlier health needs of people in deprived areas. For more about the Tower Hamlets Save Our Surgery campaign, visit their facebook page https://www.facebook.com/SaveOurGPsurgeries BMJ Voices is a...

In this podcast Alexandra Barratt, professor of public health at the University of Sydney, discusses how questions about overdiagnosis in breast cancer screening programmes were first raised 45 years ago, and why it has taken so long for the concept to become mainstream. Read her full analysis: http://www.bmj.com/content/350/bmj.h867

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 thebmj.com. Patrick Keating, a GP from Enfield, is concerned that small practices are under pressure to increase list size, but aren't able to muster resources to...

Katherine Henderson is the clinical lead of the emergency department at St Thomas's hospital in London. She worries that lack of ward space is having a domino effect throughout A and E and is the cause of increased waiting time for both patients and ambulances. If you would like to contribute to this collection, please email a brief audio...

The future of health and social care looks certain to be a defining issue in the forthcoming UK general election. Social care has been subject to deep public spending cuts, raising concerns about the sustainability of services in the future. Whoever wins the next election will need to grapple with providing joined up health and social care...

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...

Elder abuse is often the result of the organisation of health systems rather than the fault of individuals, argue Jolanda Lindenberg and Rudi Westendorp, two authors of a recent analysis paper. They call for system abuse to be acknowledged and addressed by incorporating older people’s views when designing health services. Read the full...

Around two fifths of the world’s population (those in tropical and subtropical countries), or up to 2.5 billion people, are at risk of dengue infection. An estimated 50 million infections occur annually worldwide, with 0.5 million of these cases being admitted to hospital for dengue haemorrhagic fever. Approximately 90% of these cases are in...

They have a big impact on the diet of American citizens, and those of most Western nations, so why does the expert advice underpinning US government dietary guidelines not take account of all the relevant scientific evidence asks Nina Teicholz. Read the full investigation: http://www.bmj.com/content/351/bmj.h4962

The current orthodoxy is that home is the best and preferred place of death for most people, but in this podcast, Kristian Pollock a sociologist from Nottingham University questions these assumptions and calls for greater attention to improving the experience of dying in hospital and elsewhere. Read the full...

Doctors considering strike action may worry about the effect on patients. David Metcalfe and colleagues examine the evidence and find that “patients do not come to serious harm during industrial action provided that provisions are made for emergency care.” Read the full analysis: http://www.bmj.com/content/351/bmj.h6231

PTSD may develop after exposure to exceptionally threatening or horrifying events. About 3% of the adult population has PTSD at any one time, and more than 50% in survivors of rape. In this podcast Jonathan Bisson, professor of psychiatry at the School of Medicine in Cardiff joins us to talk about the evidence for diagnosis and treatment, and...

Around half of people aged over 75 meet the diagnostic criteria for chronic kidney disease (CKD), but there is debate about what this means for patients as only a proportion of elderly people with CKD will have clinically important outcomes as a result. In this podcast, Dr Arif Khwaja argues that for CKD in the elderly, we should focus on...

Gareth Iacobucci talks to Candace Imison, director of policy at The Nuffield Trust, about the problems facing GPs, and how primary care could be changed. "5 minutes with... Candace Imison": http://www.bmj.com/content/352/bmj.i1378

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...

As France has moved in recent weeks to clear camps where migrants stay while trying to cross illegally into Britain, Médecins Sans Frontières has just opened a new one. Sophie Arie talks to Caroline Gollé, medical coordinator at the Médecins Sans Frontières​ La Linière camp​. Read more about the camp: http://www.bmj.com/content/352/bmj.i1696

Medical error is not included on death certificates or in rankings of cause of death. Martin Makary, professor of surgery at Johns Hopkins University School of Medicine, joins us to explain why we don't measure medical error, and why it is so important that we start. Read the full analysis: http://www.bmj.com/content/353/bmj.i2139

Katja Iversen, CEO of Women Deliver, joins Rebecca Coombes to explain why the UN sustainable development goals are unachievable if we don't empower women and girls to take control of their health, wellbeing, and reproductive rights. http://womendeliver.org/

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.

Global evidence indicates that mandated treatment of drug dependence conflicts with drug users’ human rights and is not effective in treating addiction. Karsten Lunze, associate professor at the Boston University School of Medicine, joins us to describe the evidence, and why he is convinced seemingly counter intuitive hard reduction...

Delirium is common in the last weeks or days of life. It can be distressing for patients and those around them. A clinical update explains why successful management involves excluding reversible causes of delirium and balancing drugs that may provoke or maintain delirium while appreciating that most patients want to retain clear cognition at the...

The same piece of evidence may reach you via a journalist, or via your doctor - but the way in which that evidence is communicated is changed by your relationship between that person. Julia Beluz from Vox and Victor Montori from the Mayo Clinic join us to discuss if it's possible to reconcile those competing points of view.

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...

Oversimplification and lack of evidence stigmatise people with mental illness and impede prevention efforts, says Simon Wessley, professor of psychiatry at King's College London, in an editorial published on thebmj.com. Read the full editorial: http://www.bmj.com/content/354/bmj.i4869