MANILA (AP): The Philippines’ largest TV and radio network, which was shutdown this week by a government regulator, asked the Supreme Court on Thursday to allow it to return to the air amid an uproar over its closure. ABS-CBN Corp said in its...

In our accompanying roundtable discussion,we hear views from a group of patients and clinicians based largely in the UK on the actions required  to advance  progress towards providing patient centred care. To extend the conversation we talked to members of the BMJ's international patient advisory panel and other patient advocates - and what...

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,...

Nick Oliver, consultant diabetologist at Imperial Healthcare NHS Trust and Philippa Cooper, who has type I diabetes, join us to explain how structured education works for patients, and give tips on self management. Read the full review: http://www.bmj.com/content/352/bmj.i998

The BMJ publishes a lot of educational articles, and in an attempt to help you with your CPD, we have put together this round-up. Our authors and editors will reflect on the key learning points in the articles we discuss, and explain how they may change their practice in light of that new understanding. In this week's round up we're...

Around 1 in 10 children and young people worldwide have mental health difficulties that substantially affect their lives. Child mental health services often concentrate on risk reduction, at the expense of the wider aspects of a child's wellbeing. As part of the high integrity healthcare series, this podcast focuses on novel ways of providing...

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,...

Assessing young people with possible eating disorders can be complex for a variety of reasons. Building a therapeutic relationship with a young person with a possible eating disorder and their family is key to enabling a thorough assessment and ongoing management, but it introduces difficult issues regarding confidentiality and risk. In this...

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...

In 2016, from an estimated pre-war population of 22 million, the United Nations (UN) identified 13.5 million Syrians requiring humanitarian assistance, of which more than 6 million are internally displaced within Syria, and around 5 million are refugees outside of Syria. In this podcast, Aula Abarra, consultant in infectious disease from London,...

Patients who are depressed and prescribed antidepressants may report weight gain, but there has been limited research into the association between the two. However new observational research published on bmj.com aims to identify that association. Rafael Gafoor, a psychiatrist and researcher at Kings College London, and one of the authors of that...

As Syria enters its ninth year of conflict, doctors are struggling to provide health care to a badly damaged country. While dealing with medicine shortages, mass casualties and everything that comes with working in a warzone, healthcare facilities and their staff are also facing an unprecedented number of targeted and often repeated attacks....

Cochrane Austria have been asking the public what they'd like to know about health. Not whether the latest drug is more efficacious, but whether glacier stone power cures hangovers. Gerald Gartlehner, director of the Cochrane Austria Centre joins us to explain what they do, and how their evidence has been received. Read more about the project...

At EBM live recently, we ran a workshop with researchers, patients and clinicians to talk about patient rights in research - should patients be setting the full research agenda? Should they be full participants and authors? Helen Macdonald, BMJ’s UK research editor and co-host of our talk evidence podcast sat down to Paul Wicks, researcher and...

In this week's special episode of Sharp Scratch, we've got something a little different for you! Last week the panel talked microaggressions, so this week we're hearing from an expert guest who is leading the work the NHS is doing to combat inequality in healthcare. If you like this special edition, let us know on Facebook, Instagram or Twitter...

We all know we should be doing more exercise, and one way to do that is by active commuting - journeying to work on foot or by bike. One thing preventing people from taking up cycling is the fear of being involved in road traffic accidents, and that the risk isn't worth the benefit of the extra exercise. It’s even more confusing when air...

A new podcast from The BMJ, to help GP's feel more connected, heard, and supported. Subscribe on; Apple podcasts - https://bit.ly/applepodsDBI Spotify - https://bit.ly/spotifyDBI Google podcasts - https://bit.ly/googlepodsDBI In our first episode, we discuss the highs and lows of video consultations, and how coronavirus has altered the landscape...

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

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

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

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

Edmond Campbell/Senior Parliamentary Reporter Conceding that healthcare workers in the public sector are burnt out as they combat COVID-19, Health and Wellness Minister Dr Christopher Tufton says the Government is taking steps to boost its...

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...

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.

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

Reds manager David Bell has great corner outfield depth, but he doesn't have a regular center fielder. Determining who will get to play where and sorting out the log jam should be a challenge for Bell in his first season as a skipper in the big leagues.

THE EDITOR, Madam: The right to education, decent work, an adequate standard of living, and housing all fall within the realm of economic, social, and cultural rights (ESCRs) guaranteed under the International Covenant on Economic, Social and...

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.

Insulin-induced hypoglycemia leads to far-ranging negative consequences in patients with diabetes. Components of the counterregulatory response (CRR) system that help minimize and reverse hypoglycemia and coordination between those components are well studied but not yet fully characterized. Here, we tested the hypothesis that acyl-ghrelin, a hormone that defends against hypoglycemia in a preclinical starvation model, is permissive for the normal CRR to insulin-induced hypoglycemia. Ghrelin knockout (KO) mice and wild-type (WT) littermates underwent an insulin bolus-induced hypoglycemia test and a low-dose hyperinsulinemic-hypoglycemic clamp procedure. Clamps also were performed in ghrelin-KO mice and C57BL/6N mice administered the growth hormone secretagogue receptor agonist HM01 or vehicle. Results show that hypoglycemia, as induced by an insulin bolus, was more pronounced and prolonged in ghrelin-KO mice, supporting previous studies suggesting increased insulin sensitivity upon ghrelin deletion. Furthermore, during hyperinsulinemic-hypoglycemic clamps, ghrelin-KO mice required a 10-fold higher glucose infusion rate (GIR) and exhibited less robust corticosterone and growth hormone responses. Conversely, HM01 administration, which reduced the GIR required by ghrelin-KO mice during the clamps, increased plasma corticosterone and growth hormone. Thus, our data suggest that endogenously produced acyl-ghrelin not only influences insulin sensitivity but also is permissive for the normal CRR to insulin-induced hypoglycemia.

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow–derived CD133⁺ and CD34⁺ endothelial progenitor cells and Ym1/2⁺ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.

29 October 2014

The Ghanaian government has taken a number of important steps to reduce illegal logging and related trade but a number of enforcement and administrative challenges remain, as well as broader governance challenges including corruption.

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.

It was the eighth inning of a late September game against the Dodgers when D-backs right-hander Yoan Lopez showed that not only might he have the stuff to be a future closer, but also the moxie of one as well.

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...

The number of people in Germany infected with covid-19, could be 10 times higher than official government estimates, according to a new study by University of Bonn researchers.1The Heinsberg study is...

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). ¹⁸F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-¹⁸F-fluoroethyl)-l-tyrosine (¹⁸F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-¹¹C-methyl)-l-methionine (¹¹C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for ¹⁸F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-¹⁸F-fluoro-l-phenylalanine (¹⁸F-FDOPA); and 100% and 70%–88%, respectively, for ¹¹C-choline. Conclusion: ¹⁸F-FET and ¹¹C-MET, both amino-acid tracers, showed a comparably higher sensitivity than ¹⁸F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, ¹⁸F-FET and ¹¹C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.

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.

β-Cell antigen recognition by autoreactive T cells is essential in type 1 diabetes (T1D) pathogenesis. Recently, insulin hybrid peptides (HIPs) were identified as strong agonists for CD4 diabetogenic T cells. Here, using BDC2.5 transgenic and NOD mice, we investigated T-cell recognition of the HIP2.5 epitope, which is a fusion of insulin C-peptide and chromogranin A (ChgA) fragments, and compared it with the WE14 and ChgA_29–42 epitopes. We measured in situ two-dimensional affinity on individual live T cells from thymus, spleen, pancreatic lymph nodes, and islets before and after diabetes. Although preselection BDC2.5 thymocytes possess higher affinity than splenic BDC2.5 T cells for all three epitopes, peripheral splenic T cells maintained high affinity only to the HIP2.5 epitope. In polyclonal NOD mice, a high frequency (~40%) of HIP2.5-specific islet T cells were identified at both prediabetic and diabetic stages comprising two distinct high- and low-affinity populations that differed in affinity by 100-fold. This high frequency of high- and low-affinity HIP2.5 T cells in the islets potentially represents a major risk factor in diabetes pathogenesis.

THE SWITCH towards liquefied natural gas, LNG, as fuel to produce power supplies for Jamaica has a downside for electricity customers, who are largely missing out on the big oil savings. The near two-thirds plunge in oil prices will have limited...

FOUR MORE applicants are vying to provide mobile payment services in various formats, including one applicant seeking to use phone credit as a cash equivalent, but successful applicants will fall under a new framework the regulator calls its “...

Members Event

Event participants

Rory Stewart, Member of Parliament for Penrith and The Border (2010-19); Secretary of State for International Development (2019)

Chair: Daniel Bruce, Chief Executive, Transparency International UK

Invitation Only Research Event