Effectiveness of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS) : a cluster randomised controlled trial

Background: Delivering high quality and evidence based healthcare to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive enhanced care package in UK general practice in improving cardiovascular risk factors in South Asian patients with type 2 diabetes. Methods: 21 inner city practices were randomised to intervention (enhanced practice nurse time, link worker and diabetes specialist nurse support) (n=868) or control (standard care) (n=618) groups. Prescribing algorithms with clearly defined targets were provided for all practices. Main outcome measures comprised changes in blood pressure, total cholesterol and glycaemic control (HbA1c) after 2 years. Findings: At baseline, groups were similar with respect to age, sex and cardiovascular risk factors. Comparing treatment groups, after adjustment for confounders, and clustering, differences in diastolic blood pressure (1.91mmHg, P=0.0001) and mean arterial pressure (1.36mmHg, P=0.0180) were significant. There were no significant differences between groups for total cholesterol or HbA1c. Economic analysis indicates the nurse-led intervention was not cost-effective. Across the whole study population systolic blood pressure, diastolic blood pressure and cholesterol decreased significantly by 4.9mmHg, 3.8mmHg and 0.45mmol/L respectively, but there was no change in HbA1c. Interpretation: Additional, although limited, benefits were observed from our culturally enhanced care package over and above the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to maximise healthcare outcomes in South Asian patients with diabetes

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

Aortic root surgery in septuagenarians: impact of different surgical techniques

<p>Abstract</p> <p>Background</p> <p>To evaluate the impact and safety of different surgical techniques for aortic root replacement (ARR) on early and late morbidity and mortality in septuagenarians undergoing ARR.</p> <p>Methods</p> <p>Ninety-five patients (73.8 ± 3.2 years) were operated and divided into three groups according to the aortic root procedure; MECH-group (n = 51) patients with a mechanical composite graft, BIO-group (n = 22) patients with a customized biological composite graft, and REIMPL-group (n = 22) patients with a valve sparing aortic root reimplantation (David I). In 42.1% (40/95) of these patients the aortic arch was replaced. Follow-up was completed in 95.2% (79/83) of in-hospital survivors.</p> <p>Results</p> <p>Hospital mortality was 12.6% (12/95) in the entire population (MECH. 15.7% (8/51), BIO 19.7% (4/22), REIMPL 0% (0/22); p = 0.004). Two patients died intraoperatively. The most frequent postoperative complications were prolonged mechanical ventilation ((>48 h) in 16.8% (16/93) (MECH. 7% (7/51), BIO 36.4% (8/22), REIMPL 4.5% (1/22); p = 0.013) and rethoracotomy for postoperative bleeding in 12.6% (12/95) (MECH. 12% (6/51), BIO 22.7% (5/22), REIMPL 4.5% (1/22); p = 0.19). Nineteen late deaths (22.9%) (19/83) (MECH 34.8% (15/43), BIO 16.7% (3/18), REIMPL 4.5% (1/22); p = 0.012) occurred during a mean follow-up of 41 ± 42 months (MECH 48 ± 48 months, BIO 25 ± 37 months, REIMPL 40 ± 28 months, p = 0.028). Postoperative NYHA class decreased significantly (p = 0.017) and performance status (p = 0.027) increased for the entire group compared to preoperative values.</p> <p>Conclusion</p> <p>Our data indicate that valve sparing aortic root reimplantation is safe and effective in septuagenarians, and is associated with low early and late morbidity and mortality.</p

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell

Association of Inherited Variation in Toll-Like Receptor Genes with Malignant Melanoma Susceptibility and Survival

The family of Toll-like receptors (TLRs) is critical in linking innate and acquired immunity. Polymorphisms in the genes encoding TLRs have been associated with autoimmune diseases and cancer. We investigated the genetic variation of TLR genes and its potential impact on melanoma susceptibility and patient survival. The study included 763 cutaneous melanoma cases recruited in Germany and 736 matched controls that were genotyped for 47 single nucleotide polymorphisms (SNPs) in 8 TLR genes. The relationship between genotype, disease status and survival was investigated taking into account patient and tumor characteristics, and melanoma treatment. Analysis of 7 SNPs in TLR2, 7 SNPs in TLR3 and 8 SNPs in TLR4 showed statistically significant differences in distribution of inferred haplotypes between cases and controls. No individual polymorphism was associated with disease susceptibility except for the observed tendency for TLR2-rs3804099 (odds ratio OR  = 1.15, 95% CI 0.99–1.34, p = 0.07) and TLR4-rs2149356 (OR = 0.85, 95% CI 0.73–1.00, p = 0.06). Both polymorphisms were part of the haplotypes associated with risk modulation. An improved overall survival (Hazard ratio HR 0.53, 95% CI 0.32–0.88) and survival following metastasis (HR 0.55, 95% CI 0.34–0.91) were observed in carriers of the variant allele (D299G) of TLR4-rs4986790. In addition various TLR2, TLR4 and TLR5 haplotypes were associated with increased overall survival. Our results point to a novel association between TLR gene variants and haplotypes with melanoma survival. Our data suggest a role for the D299G polymorphism in the TLR4 gene in overall survival and a potential link with systemic treatment at stage IV of the disease. The polymorphic amino acid residue, located in the ectodomain of TLR4, can have functional consequences

Intentional Weight Loss and Dose Reductions of Anti-Diabetic Medications – A Retrospective Cohort Study

BACKGROUND AND AIM: Intentional weight loss, primarily by improving insulin resistance, is known to decrease the need for anti-diabetic medications. In this study, we assess the magnitude of weight loss that resulted in dose reductions or discontinuation of anti-diabetic medications in overweight or obese patients with type 2 diabetes (DM) undergoing weight loss treatment. METHODS: Case records of 50 overweight or obese patients with DM who successfully decreased dosage or discontinued diabetes medications after losing weight via attendance at two University-based, outpatient weight management centers were analyzed. Follow-up visits, weight reduction interventions, and decisions for dose reductions or discontinuation of medications were individualized to patient needs by the treating physician. RESULTS: Mean starting BMI was 35 kg/m(2), mean age 53.4 years, and 58% were male. All 50 used at least one anti-diabetic medication (30 metformin, 39 sulfonylureas, 31 insulin, 21 sitagliptin) to manage blood sugar. Mean duration of follow-up was 30.2 months. Mean weight loss was 10.8 ± 4.1 kgs (11.1% of initial body weight ± 4.7%). 22/50 patients (44%) discontinued anti-diabetes medications (14 sulfonylureas [36%], 7 insulin [23%], 4 sitagliptin [19%]). The mean percentage weight loss achieved at the point of successful discontinuation of medication was 11.2% ± 3.5% (14% for sulphonylureas, 11% for insulin, and 7.1% for sitagliptin). Mean percentage weight loss of 5.6% ± 2.8% (5.1% for sulphonylureas, 4.3% for insulin, and 7.1% for sitagliptin) was required for initial dose reduction. For every 5% weight loss, predicted dose reductions were sulphonylureas, 39%; insulin, 42%; and any anti-diabetic medications, 49%. CONCLUSION: Among overweight or obese patients with type 2 diabetes, intentional weight loss of 7-14% was typically required for full discontinuation of at least one anti-diabetic medication. Discontinuation of insulin was achieved at a mean weight reduction of 11% of initial body weight

Spine neck plasticity regulates compartmentalization of synapses

Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization