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...

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...

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death

J. Denis McGarry
Jan 1, 2002; 51:7-18
Banting Lecture 2001

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

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes

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

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA_1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA_1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.

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.

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified two further patients with de novo EIF2B1 variants. In addition to having diabetes, four of five patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditions and triggers expression of stress response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.

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.

Vendors and store operators who would normally score big on Mother’s Day baskets are lamenting that the novel coronavirus has put a dent in their sales. Kaydyonne Thomas, owner of a gift store in the Pavilion Mall, located in Half Way Tree, said...

Director of the Pan American Health Organization (PAHO), Dr Carissa F. Etienne, today called for accelerated and expanded testing for COVID-19 in countries of the Americas. “We need a clearer view of where the virus is circulating and how...

PORT AU PRINCE, Haiti, CMC – The Government of Haiti has received funds amounting to US$16.1 million from the United States to help the country respond to the COVID-19 pandemic. The funds from the United States Agency for International...

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 AU PRINCE, Haiti, CMC – The Ministry of Public Health has confirmed that a 20-year-old man has become the seventh person in Haiti to die of the coronavirus (COVID-19). It is urging the population to follow restriction measures, including...

PORT OF SPAIN, Trinidad, CMC – The Trinidad and Tobago government Saturday said it had uncovered a plot by persons to defraud the state and that a new mechanism would be put in place Monday in providing rental assistance to people impacted by...

HAMILTON, Bermuda, CMC –  Bermuda recorded its seventh COVID-19 death on Saturday as Finance Minister Curtis Dickinson announced that he would need to rewrite this year’s budget because of the battering from the global...

As of May 6, officials in Nevis are reporting that there are no active cases of the deadly COVID-19 virus on the island. This was confirmed Tuesday by Premier Mark Brantley, Minister responsible for Health, in the Nevis Island Administration....

KINGSTOWN, St Vincent, CMC – St Vincent and the Grenadines students in Jamaica wanting to return home amid the coronavirus (COVID-19, including locked borders, must each pay an estimated US$1,3339 for a return flight. In a letter to the...

Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein–coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.

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.

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.

Few figures in baseball history have accomplished as much as Frank Robinson. A feared slugger, a World Series champion, a pioneer for minority managers and an ambassador for the game, Robinson had an impact that can be felt in all corners of the sport.

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

Reds starting pitcher Anthony DeSclafani hated how his 2018 season ended and didn't need any motivation to make improvements over the winter.

Even before the Reds underscored their determination to improve by making major offseason acquisitions for the club, first baseman Joey Votto was already working to improve his hitting and his overall game.

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: THE JAMAICAN economy has been underperforming for the last 40 years, during which economic growth averaged approximately one per cent per annum. One of the main reasons for this poor performance is the non-competitive nature of...

As the global battle against the deadly COVID-19 disease wages on, with each country’s government, healthcare industry, and general public playing its part in defeating this new and relatively unknown enemy, two seemingly unlikely foot soldiers...

The BMP2/4 antagonist and novel adipokine Gremlin 1 is highly expressed in human adipose cells and increased in hypertrophic obesity. As a secreted antagonist, it inhibits the effect of BMP2/4 on adipose precursor cell commitment/differentiation. We examined mRNA levels of Gremlin 1 in key target tissues for insulin and also measured tissue and serum levels in several carefully phenotyped human cohorts. Gremlin 1 expression was high in adipose tissue, higher in visceral than in subcutaneous tissue, increased in obesity, and further increased in type 2 diabetes (T2D). A similar high expression was seen in liver biopsies, but expression was considerably lower in skeletal muscles. Serum levels were increased in obesity but most prominently in T2D. Transcriptional activation in both adipose tissue and liver as well as serum levels were strongly associated with markers of insulin resistance in vivo (euglycemic clamps and HOMA of insulin resistance), and the presence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We also found Gremlin 1 to antagonize insulin signaling and action in human primary adipocytes, skeletal muscle, and liver cells. Thus, Gremlin 1 is a novel secreted insulin antagonist and biomarker as well as a potential therapeutic target in obesity and its complications T2D and NAFLD/NASH.

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H₂O₂) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H₂O₂ by high glucose, and H₂O₂ reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

13 July 2016

The updated Guidelines focus on eight key objectives for the petroleum sector in emerging producing countries and include policy-oriented recommendations for each objective.

Invitation Only Research Event

Jackie Robinson was born a century ago this Jan. 31. To commemorate the 100th anniversary of the birth of one of baseball's most important pioneers, Major League Baseball has planned a yearlong slate of activities in Robinson's honor.

We're bridging the gap between our Top 100 and organizational Top 30 lists this week with a look at each club's next best top prospect who didn't make the Top 100.

The D-backs signed veteran free-agent reliever Greg Holland to a one-year contract on Thursday.

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.

When you think of the D-backs, what players spring to mind? Luis Gonzalez, Randy Johnson, Paul Goldschmidt and Matt Williams are probably some of the names that arise. But what names are familiar to baseball fans but might have even some D-backs fans saying, "He was a Diamondback?"

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

The Arizona Diamondbacks agreed to terms with catcher Caleb Joseph on a one-year contract. To make room for Joseph on the roster, the D-backs placed right-hander Taijuan Walker on the 60-day injured list. The D-backs' 40-man roster remains at 40.

They've talked in small groups. They've talked in larger groups. The front office has discussed it. It's a topic that kept manager Torey Lovullo up at night at times. What in the world happened to the D-backs last September when they watched the National League West Division lead slip away during an 8-19 finish?

The mothballing of Britain’s Nightingale hospitals, some of which have yet to treat a single covid-19 patient, has raised questions about whether resources to fight the pandemic were...

bmj;369/may07_6/m1803/FAF1faPhoto credit: Abbas GhazanfarOn 25 March Adil El-Tayar, a renowned organ transplantation specialist, became the first working NHS surgeon to die from covid-19 in hospital...