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.

The Astros logo outside the Ballpark of the Palm Beaches really is something to see, all the way from Haverhill Rd. The closer you get the bigger it gets, the white "H" right there in front of the huge orange star. Underneath the "H" is the following message, white against orange: "2017 World Champions." It would have been a simple matter to put "2018" down there, too. There was room.

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...

HARRISBURG, Pennsylvania (AP) — A Pennsylvania inmate whose dreadlocks violated a jail’s haircut policy has been released from solitary confinement after more than a year, although his federal lawsuit is still pending. A federal...

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....

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...

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...

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...

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...

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

Medicine has long been a rewarding career, but doctors say the profession needs to overcome the frustrations of working in the NHS to ensure it remains so. During the Big Debate at BMJ Live in London last week six speakers argued for and against the motion, “This house believes that medicine is the best career in the world.” After presentations...

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,...

Underneath all of our civilisation and science, we’re still primates - and the connection between patient and doctor can be reinforced by simply taking a hand. Robin Youngson, cofounder of hearts in healthcare, and Mitzi Blennerhassett, who has written extensively on patient engagement, have co-authored an editorial calling for the humanisation...

Surrogate endpoints are commonly used in clinical trials to get quicker results, however Michael Baum, emeritus professor at University College London, worries that by not focusing on real outcomes - length of life, and quality of life - that these are being used to justify expensive treatments which may not benefit patients. Read the full...

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...

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,...

Its now widely agreed that one of the key ways of reducing the current high level of "waste " in biomedical research is to focus it more squarely on addressing the questions that matter to patients - and the people and medical staff that care for them. In this interview, Tessa Richards - the BMJ's patient partnership editor, talks 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...

The number of people estimated to be latently infected with TB - that is infected with TB, which has not yet manifested symptoms - is around 2 billion. That is 1 in 3 people on the planet are infected by the bacteria. The World Health Organization’s website notes that on average 5-10% of those infected with TB will develop active TB. That number...

In the second of our EBM round-ups, Carl Heneghan, Helen Macdonald and Duncan Jarvies are joined by Deborah Cohen, investigative journalist and scourge of device manufacturers. We're giving our verdict on the sensitivity and specificity of ketone testing for hyperemesis, and the advice to drinking more water to prevent recurrent UTIs in...

2018 will go down in history as a year of reckoning as the year that that some men’s behaviour came back to bite them. The continuing impact of #MeToo across the world has prompted another round of thinking about women’s experiences in medicine, which can be seen this year’s christmas journal In this podcast, Esther Choo and Eleni Lenos, join us...

In this EBM round-up, Carl Heneghan, Helen Macdonald and Duncan Jarvies are back to give you an update Dual vs single therapy for prevention of TIA or minor stroke - how does the advice that dual work better translate in the UK? Carl explains why Japan can teach us to get active and, how GPs can use that information to "drop a decade" in...

Change requires the application of power - the way in which individuals can accrue power has shifted in our digitally connected world. Traditional ways of influencing change in healthcare (getting the chief executive on side, having a quiet chat with the medical director) are not the only way to build a momentum. Henry Timms - author of “New...

Burnout is a problem in healthcare - it’s a problem for individuals, those who experience it and decide to leave a career they formerly loved, but it’s also a problem for our healthcare system. Burnout is associated with an increase in medical errors, and poor quality of care. Fundamentally it’s a patient safety issue. But, unlike other patient...

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...

Is it possible to have a fair price for medicines? Yes, according to a new collection just published on bmj.com. The authors set out to evaluate how we could improve the functioning of the market for medicines, to honestly compensate industry for innovation, whilst allowing the poorest to afford them. Suerie Moon, co-director of global health at...

Last week the BMJ published it’s first special edition into Racism in Medicine. The issues tacked ranged from differential attainment in medical school, to the physiological effects that experiencing everyday discrimination has. The issue was guest edited by Victor Adebowale, the Chief Executive of the social care enterprise Turning Point, and...

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...

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...

As we cover the covid-19 outbreak, we want to hear some of the stories from the frontline - And who better to heart of what this pandemic is doing to the profession in the UK, than some of the people who write regularly for The BMJ? In this first one, we wanted to look specifically at acute care - those at the sharp end of the response, so we're...

There is no doubt that anxiety levels that clinicians are feeling during this pandemic are high. One military medic believes the current situation is comparable to his experience when posted during British campaigns in Afghanistan and Iraq. Cormac Doyle offers advice on how to deal with high-stress conditions, both in a work and at home, as...

As the pandemic plays out - the way in which doctors in the UK practice is changing, hospitals are reconfigured to increase critical care capacity, GPs are working from home and doing their day to day work remotely. Some of the changes have come at the detriment of staff and patient wellbeing but covid-19 has also helped cut through some of the...

How can we help frontline clinicians? Sometimes medics may feel uneasy or even guilty and that they could be doing more. That was what a junior doctor in Abergavenny in Wales felt and she did something about it. In this podcast, we speak to Josie Cheetham about how she started her initiative to provide support boxes in hospitals for her...

As the pandemic plays out - hospitals are reconfigured to increase critical care capacity, outpatient clinics become virtual, and elective procedures delayed. How are these affecting care for those who are in hospital but don't have covid-19? In this podcast, Matt Morgan,honorary senior research fellow at Cardiff University, consultant in...

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 you...

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications

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

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article

BM Spiegelman
Apr 1, 1998; 47:507-514
Articles

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ~1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Days after The Gleaner reported a clarion call from Port Maria Mayor Richard Creary for the quarantine of St Mary communities owing to growing concerns about the spread of COVID-19 in the parish, the Government responded with the lockdown of three...

“I know this has been some difficult times for us with the pandemic, but I know we are going to get through this together – Jamaica together. We are going to continue our social distancing. We are going to continue practising our incredible hygiene...

The People’s National Party (PNP) has asserted that the absence of a quarantine order for three St Mary communities is adding to the state of confusion. The 14-day measure began on Thursday in Dover, Enfield and Annotto Bay at 6 a.m. “The lack of...

No sooner than the Government’s announced its intention to restart the economy, private sector groups are advocating for longer working hours to fast-track recovery during the COVID-19 pandemic. In a collaborative move, the Jamaica Manufacturers...

WASHINGTON, CMC – The World Bank has predicted the sharpest decline of remittances to Latin America and the Caribbean, saying that global remittances on a whole are projected to fall by about 20 percent in 2020 due to the economic crisis...