As the Jamaica and the rest of the world continue to feel the impact of COVID-19, corporate companies are stepping up in a big way, providing support and assistance to communities, individuals and other organisations that are directly or indirectly...

Dominique Roache, a Jamaican medical student living and studying in Belize, has found a new hobby since San Pedro went under complete lockdown – self-portraits. “I’ve been inside for so long, I decided to start taking pictures of myself, using...

Before COVID-19, media personality Sapphire was bringing the heat with her birthday celebration ‘Fuego’. It’s throwback Tuesday, so let’s rewind with a ‘fêting’ dose of Something Extra.

Monique Lynch is a 29-year-old who believes her purpose is to improve the lives of those around her, especially the downtrodden and persons living with mental health issues. This angel-on-earth in the eyes of many is a Jill of several trades as...

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.

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.

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.

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.

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...

HONOLULU (AP) — Hawaii authorities are cracking down on rogue tourists who are visiting beaches, riding personal watercraft, shopping and generally flouting strict requirements that they quarantine for 14 days after arriving. A newlywed...

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...

JAMAICA OLYMPIC Association (JOA) President Christopher Samuda believes that his sports administration experience will aid him in helping to finally shape a professional football league in the Caribbean. Concacaf announced Samuda’s appointment to...

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,...

The movement to make data from clinical trials widely accessible has achieved enormous success, and it is now time for medical journals to play their part. From 1 July The BMJ will extend its requirements for data sharing to apply to all submitted clinical trials, not just those that test drugs or devices. The BMJ's Elizabeth Loder explains what...

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...

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.

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...

Pharma companies say that money spent on promotion is essential to educate doctors about the best drugs - but when a medical student asked Joseph Ross, associate professor of medicine and public health at Yale, if those companies are promoting the right drugs for that message to be true, the answer wasn't available. Ross and Tyler Greenaway, his...

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...

An “author pays” publishing model is the only fair way to make biomedical research findings accessible to all, say David Sanders, professor of gastroenterology at Sheffield University, but James Ashton and worries that it can lead to bias in the evidence base towards commercially driven results - as those are the researchers who can pay for open...

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...

We are more than six weeks into the lockdown and if you were to gauge the mood of the nation, it would be one of fatigue. It started as an all-hands-on-deck emergency situation, but it now transpires that the current work situation for healthcare professionals is not going to change any time soon. This is a marathon rather than a sprint. So how...

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

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

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article

Most replicated genetic determinants for type 1 diabetes are common (minor allele frequency [MAF] >5%). We aimed to identify novel rare or low-frequency (MAF <5%) single nucleotide polymorphisms with large effects on risk of type 1 diabetes. We undertook deep imputation of genotyped data followed by genome-wide association testing and meta-analysis of 9,358 type 1 diabetes case and 15,705 control subjects from 12 European cohorts. Candidate variants were replicated in a separate cohort of 4,329 case and 9,543 control subjects. Our meta-analysis identified 27 independent variants outside the MHC, among which 3 were novel and had MAF <5%. Three of these variants replicated with P_replication < 0.05 and P_combined < P_discovery. In silico analysis prioritized a rare variant at 2q24.3 (rs60587303 [C], MAF 0.5%) within the first intron of STK39, with an effect size comparable with those of common variants in the INS and PTPN22 loci (combined [from the discovery and replication cohorts] estimate of odds ratio [OR_combined] 1.97, 95% CI 1.58–2.47, P_combined = 2.9 x 10^–9). Pharmacological inhibition of Stk39 activity in primary murine T cells augmented effector responses through enhancement of interleukin 2 signaling. These findings provide insight into the genetic architecture of type 1 diabetes and have identified rare variants having a large effect on disease risk.

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (P_interaction = 3.7 x 10^–4). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia.

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...

DOVER, St Mary: Residents of Epsom and Dover in St Mary are on edge, but have accepted quarantine measures imposed by the Government to curtail the spread of the dreaded coronavirus in that parish. Security checkpoints at both ends of the parish...

Director of the Pan American Health Organization (PAHO), Carissa Etienne, today urged for vaccination programmes to continue during the COVID-19 pandemic. “If we fall behind on routine immunisations, particularly for children, we risk...

PORT OF SPAIN, Trinidad, CMC – Prime Minister Dr Keith Rowley Saturday dismissed as a “dishonest last gasp and gamble of a dangerously delusional woman” a statement by Opposition Leader Kamla Persad Bissessar calling for him...

It was only five years ago that the Cardinals won the National League Central with only 90 wins. Heck, it was only 12 years ago that the Cubs won it with 85, and 13 that the Cardinals won it with 83. Point is: There have been times in recent baseball history that the NL Central was not exactly the toughest gauntlet in the sport. But in 2019, it looks like the scariest division in baseball.

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.

The COVID-19 pandemic around the world has taken the world by storm, touching the lives of every human being on Earth. The global nature of the crisis has united us as human beings and tragedy and deaths in any country by COVID-19 worry us all....

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine," signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.

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.

Invitation Only Research Event

Event participants

Paula Hodges QC, Partner; Head, Global Arbitration Practice, Herbert Smith Freehills
Stéphane Brabant, Partner; Chairman, Africa Practice Group, Herbert Smith Freehills

Invitation Only Research Event

Invitation Only Research Event

Jake Lamb's education at first base hit another checkpoint during Monday's initial full-squad workout when he went through bunt drills for the first time.

The present study examined the predictive values of amyloid PET, ¹⁸F-FDG PET, and nonimaging predictors (alone and in combination) for development of Alzheimer dementia (AD) in a large population of patients with mild cognitive impairment (MCI). Methods: The study included 319 patients with MCI from the Alzheimer Disease Neuroimaging Initiative database. In a derivation dataset (n = 159), the following Cox proportional-hazards models were constructed, each adjusted for age and sex: amyloid PET using ¹⁸F-florbetapir (pattern expression score of an amyloid-β AD conversion–related pattern, constructed by principle-components analysis); ¹⁸F-FDG PET (pattern expression score of a previously defined ¹⁸F-FDG–based AD conversion–related pattern, constructed by principle-components analysis); nonimaging (functional activities questionnaire, apolipoprotein E, and mini-mental state examination score); ¹⁸F-FDG PET + amyloid PET; amyloid PET + nonimaging; ¹⁸F-FDG PET + nonimaging; and amyloid PET + ¹⁸F-FDG PET + nonimaging. In a second step, the results of Cox regressions were applied to a validation dataset (n = 160) to stratify subjects according to the predicted conversion risk. Results: On the basis of the independent validation dataset, the ¹⁸F-FDG PET model yielded a significantly higher predictive value than the amyloid PET model. However, both were inferior to the nonimaging model and were significantly improved by the addition of nonimaging variables. The best prediction accuracy was reached by combining ¹⁸F-FDG PET, amyloid PET, and nonimaging variables. The combined model yielded 5-y free-of-conversion rates of 100%, 64%, and 24% for the low-, medium- and high-risk groups, respectively. Conclusion: ¹⁸F-FDG PET, amyloid PET, and nonimaging variables represent complementary predictors of conversion from MCI to AD. Especially in combination, they enable an accurate stratification of patients according to their conversion risks, which is of great interest for patient care and clinical trials.

We aimed to assess the value of ¹¹C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on ^99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUV_max and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the ¹¹C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUV_max was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that ¹¹C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and ^99mTc-sestamibi imaging yield negative or discordant results.

M2 macrophages play an important role in tissue repair and regeneration. They have also been found to modulate β-cell replication in mouse models of pancreatic injury and disease. We previously reported that β-cell replication is strongly increased in a subgroup of human organ donors characterized by prolonged duration of stay in an intensive care unit (ICU) and increased number of leukocytes in the pancreatic tissue. In the present study we investigated the relationship between duration of stay in the ICU, M2 macrophages, vascularization, and pancreatic cell replication. Pancreatic organs from 50 donors without diabetes with different durations of stay in the ICU were analyzed by immunostaining and digital image analysis. The number of CD68⁺CD206⁺ M2 macrophages increased three- to sixfold from ≥6 days’ duration of stay in the ICU onwards. This was accompanied by a threefold increased vascular density and a four- to ninefold increase in pancreatic cells positive for the replication marker Ki67. A strong correlation was observed between the number of M2 macrophages and β-cell replication. These results show that a prolonged duration of stay in the ICU is associated with an increased M2 macrophage number, increased vascular density, and an overall increase in replication of all pancreatic cell types. Our data show evidence of marked levels of tissue repair in the human donor pancreas.

Type 1 diabetes is an autoimmune-mediated disease that culminates in the targeted destruction of insulin-producing β-cells. CD4 responses in NOD mice are dominated by insulin epitope B:9-23 (InsB_9-23) specificity, and mutation of the key T-cell receptor (TCR) contact residue within the epitope prevents diabetes development. However, it is not clear how insulin self-antigen controls the selection of autoimmune and regulatory T cells (Tregs). Here we demonstrate that mutation of insulin epitope results in escape of highly pathogenic T cells. We observe an increase in antigen reactivity, clonality, and pathogenicity of insulin-specific T cells that develop in the absence of cognate antigen. Using a single TCR system, we demonstrate that Treg development is greatly diminished in mice with the Y16A mutant epitope. Collectively, these results suggest that the tyrosine residue at position 16 is necessary to constrain TCR reactivity for InsB_9-23 by both limiting the development of pathogenic T cells and supporting the selection of Tregs.

GEORGETOWN, Guyana (AP): Four months after Guyana became one of the world’s newest crude oil exporters, the South American country says it is already reaping the rewards with about $60 million in payments. The money is linked to Guyana’s...

A joint Chatham House-RUSI project that focuses on strengthening common understanding across the Atlantic and develop new ideas for how the US and Europe can better engage with and respond to China’s rise.

More on Transatlantic Dialogue on China

Members Event

Event participants

Anu Bradford, Author, The Brussels Effect: How the European Union Rules the World; Henry L. Moses Professor of Law and International Organization, Columbia Law School

Creon Butler, Research Director, Trade, Investment & New Governance Models; Director, Global Economy and Finance Programme, Chatham House

Chair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House