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?

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.

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.

There won't be many roster battles when the Astros open camp later this week, and they won't be decided until the final days of the team's stay in West Palm Beach, Fla. Houston has an open competition for its fifth starter spot heading into Spring Training, and the club also has to sort out a crowded outfield and the final spots in the bullpen.

With this many stars and this much talent, you can't help but have visions of playing baseball deep into October. And considering it was only a year ago the Astros were talking about defending their World Series title, their window to win another one remains wide open.

Astros outfielder Josh Reddick vows to start hitting to the opposite field more this year, which is something he did well in 2017, but not '18. Reddick hit .242 with 17 homers and 47 RBIs last year after hitting .314 with 13 homers and 82 RBIs to help the Astros to the World Series title in '17.

HYDERABAD, India (AP) — A gas leak at a chemical factory owned by a South Korean company in southern India early Thursday left at least 11 people dead and about 1,000 struggling to breathe. The chemical styrene, used to make plastic and...

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,...

"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,...

As the NHS strains under pressure from rising patient activity, an ageing population, and financial constraints, The BMJ hosted a discussion on how clinicians should be helping to manage demand at last week’s Nuffield Trust health policy summit. Taking part are: - Eileen Burns, president of the British Geriatrics Society - Andrew Fernando, GP...

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...

Mike Richards is well known in the UK - former Cancer Tzar, he now heads up the Care Quality Commission - regulator of all health and social care services, and therefore the body responsible for inspecting hospitals and GP practices. In this interview, BMJ’s head of news and views, Rebecca Coombes went to the CQC’s headquarters in London, and...

Virginia Murray, public health consultant in global disaster risk reduction at Public Health England, was instrumental in putting together the Sendai Framework for Disaster Risk Reduction - an international agreement which aims to move the world from reacting to disasters, to proactively preventing them. In this podcast, she explains what they...

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...

This week influential Editor-in-Chief of JAMA Internal Medicine Dr Rita Redberg joins Ray for a wide ranging conversation on all things health. A Professor at the University of California San Francisco and high profile contributor to The Washington Post and New York Times, Rita is also a practising cardiologist who loves to see patients. She says...

WHO Director-General Dr. Tedros recently said “Since it came into force 13 years ago, the Framework Convention on Tobacco Control remains one of the world’s most powerful tools for promoting public health,”. But is it? That’s what a to studies just published on bmj.com try and investigate - one of which pulls together all the data we have on...

Margaret Heffernan has thought a lot about whistleblowing, and why companies don't respond well to it. She wrote the "Book Wilful Blindness: Why We Ignore the Obvious at our Peril". In this podcast she talks about how culture, and groupthink, leads to a culture where whistleblowers are ignored, and why the NHS needs to change the way it treats...

There comes a tipping point in all campaigns when the evidence is overwhelming and the only way to proceed is with action. According to David Williams, it’s time to tackle the disproportionate effects of race on patients in the UK. David Williams, from Harvard University, developed the Everyday Discrimination Scale that, in 1997, launched a new...

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications

Franz M Matschinsky
Feb 1, 1996; 45:223-241
Banting Lecture 1995

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

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

This study aims to model genetic, immunologic, metabolomics, and proteomic biomarkers for development of islet autoimmunity (IA) and progression to type 1 diabetes in a prospective high-risk cohort. We studied 67 children: 42 who developed IA (20 of 42 progressed to diabetes) and 25 control subjects matched for sex and age. Biomarkers were assessed at four time points: earliest available sample, just prior to IA, just after IA, and just prior to diabetes onset. Predictors of IA and progression to diabetes were identified across disparate sources using an integrative machine learning algorithm and optimization-based feature selection. Our integrative approach was predictive of IA (area under the receiver operating characteristic curve [AUC] 0.91) and progression to diabetes (AUC 0.92) based on standard cross-validation (CV). Among the strongest predictors of IA were change in serum ascorbate, 3-methyl-oxobutyrate, and the PTPN22 (rs2476601) polymorphism. Serum glucose, ADP fibrinogen, and mannose were among the strongest predictors of progression to diabetes. This proof-of-principle analysis is the first study to integrate large, diverse biomarker data sets into a limited number of features, highlighting differences in pathways leading to IA from those predicting progression to diabetes. Integrated models, if validated in independent populations, could provide novel clues concerning the pathways leading to IA and type 1 diabetes.

Tears flowed yesterday down the face of Donaree Anderson, cousin of 15-year-old Nyron Taylor, one of two children shot dead in west Kingston hours apart on Wednesday. Eight-year-old Toya Brown was the other child killed just days into the month...

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...

Led by vice president of home clubhouse operations Rick Stowe, who began working for the club in 1981 and became head of the clubhouse in 1997, the Reds have a well-oiled machine with regard to packing up and moving out.

Reds Spring Training in Goodyear, Ariz., will feature a new manager in David Bell, a new coaching staff and several new players. Here is what you need to know about 2019 camp.

Frank Robinson is considered one of the greatest players to ever wear a Cincinnati Reds uniform. His talent and success brought dynamic change to the Reds and to our City.

One of the best catchers in baseball was available all winter in J.T. Realmuto, and the Reds were very much one of the teams in hot pursuit in trade talks with the Marlins. But on Thursday, it was the Phillies who acquired Realmuto from Miami.

Plenty of teams say they will make roster moves in the offseason to improve and then often underwhelm. No one could say that this winter about the Reds, who were arguably the busiest team during the Hot Stove season.

Here's an early look at how the Reds' 25-man roster could shape up on Opening Day.

The Reds made their signing of reliever Zach Duke official on Monday, announcing that they've signed the veteran left-hander to a one-year contract.

It wasn't just that there were new faces when Reds camp opened Tuesday with the reporting of pitchers and catchers for physicals, there was a different vibe that could be felt in the hallways and clubhouse.

Reds reliever Michael Lorenzen's top priority in Spring Training will be to get innings and prepare himself to pitch in what could be a multitude of roles. However, Lorenzen's offseason workouts also included outfield work and batting practice -- and that could continue in the spring.

As Reds Spring Training opened with pitchers and catchers reporting for physicals on Tuesday, new manager David Bell was already be tasked with many responsibilities. But there will be one that looms largest. Following five years out of the postseason, including the past four with more than 90 losses, Bell must restore a culture of winning.

Reds left-hander Alex Wood won his arbitration case over the club on Wednesday. Wood will earn $9.65 million on his one-year contract this season. Cincinnati had offered $8.7 million.

When the Reds overhauled their rotation with three offseason trades, the first deal brought right-hander Tanner Roark from the Nationals for reliever Tanner Rainey. Observers saw Roark as a solid middle-of-the rotation hurler who is steady and dependable while able to rack up innings.

The Reds want to use Raisel Iglesias in the most intense moments, even if that means using someone else in the ninth.

During some Reds pitchers fielding practice, or PFP drills, on Friday, Amir Garrett was playing first base. Alex Wood was at shortstop and Brandon Finnegan was flashing some skills all over the infield.

Utility player and Rule 5 selection Connor Joe has been working with the catchers since Reds Spring Training opened. What makes that a little more interesting is that Joe has never caught a game professionally.

Who do the Reds have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for Cincy's Top 30 Prospects on MLB Pipeline's Prospect Watch.

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.

Upon the passing of his physical on Tuesday, the Reds signed infielder/outfielder Derek Dietrich to a Minor League contract with an invitation to big league camp for Spring Training.

New Reds outfielder Yasiel Puig has been in camp for about a week, often hitting on his own on the backfields. With the first full-squad workout taking place on Monday, Puig was able to warm up, throw and hit with his teammates.

Since Jesse Winker suffered a season-ending shoulder injury on July 23, he's gained a lot of company in the corner-outfield spots.

THE EDITOR, Madam: How many more will have to suffer? How many more will have to die to end the discrimination often meted out to persons suspected of or confirmed with COVID-19? The novel coronavirus is highly contagious, seems so mysterious, and...

THE EDITOR, Madam: Words cannot describe my feeling of loss on hearing that prominent psychiatrist Professor Fred Hickling has died. Professor Hickling was one of Jamaica’s treasures through his work in the field of community mental health. His...

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

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