SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Easily scalable synthesis of Ni nanosols suitable for the hydrogenation of 4-nitrophenol to p-aminophenol under mild condition

Ni nanoparticles with a dimension ranging between 80 and 200 nm were synthesized by a microwaveassisted polyol route. The reaction was carried out at 200 C in diethylenglycol (DEG) in the presence of a binary chelating agent system (polyvinylpyrrolidone PVP and dodecylamine DDA), in order to obtain stable and highly concentrated nanosols whose ratio was carefully optimized. Stable suspensions were produced with the future prospect of improving the performance of the anodic layer in solid oxide fuel cells (SOFCs), in which the metal is employed as catalyst. Studying the influence of different reaction times on the final product, it was possible to identify the reaction path that goes through the formation, after 10 min, of crystalline Ni-glycolate that turns completely into crystalline Ni metal after 20 min. The as obtained Ni nanoparticles were characterized by XRD, TG\u2013DTA, FT-IR, TEM. Preliminary tests on their catalytic and electrochemical activities were carried out by studying the hydrogenation of 4-nitrophenol (4-NP) to p-aminophenol (4-AP) in the presence of NaBH4 as probe reaction and by calculating the electrochemically active surface area (AECSA) with cyclic voltammetry

Herpes simplex encephalitis in glioma patients: a challenging diagnosis.

OBJECTIVES: In recent years, herpes simplex encephalitis (HSE) has been reported with increasing frequency in settings of immunosuppression, such as acquired immunodeficiency, transplantation and cancer. As observed, in immunocompromised individuals HSE presents peculiar clinical and paraclinical features, and poorer prognosis. METHODS: Here we describe a retrospective series of seven cases of HSE in patients with high-grade glioma (HGG), collected among three institutions in a 5-year period (during this time, a total of 1750 patients with HGG were treated). RESULTS: Diagnosis of the condition was particularly challenging due to the confounding clinical presentation and the atypical biological findings. As a result, antiviral treatment was started with a sharp delay compared with immunocompetent hosts. Prognosis was poor, with high short-term mortality and severe residual disability in survivors. CONCLUSIONS: The substantial incidence of HSE observed in our centres together with the difficulty in diagnosing the condition suggest that the incidence of this complication may be highly underestimated. The aim of our report is to strengthen the observation of HSE in patients with HGG and outline the key elements that may allow its diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Leveraging ethnic group incidence variation to investigate genetic susceptibility to glioma: A novel candidate SNP approach.

Objectives: Using a novel candidate SNP approach, we aimed to identify a possible genetic basis for the higher glioma incidence in Whites relative to East Asians and African-Americans. Methods:  We hypothesized that genetic regions containing SNPs with extreme differences in allele frequencies across ethnicities are most likely to harbor susceptibility variants. We used International HapMap Project data to identify 3,961 candidate SNPs with the largest allele frequency differences in Whites compared to East Asians and Africans and tested these SNPs for association with glioma risk in a set of White cases and controls. Top SNPs identified in the discovery dataset were tested for association with glioma in five independent replication datasets. Results: No SNP achieved statistical significance in either the discovery or replication datasets after accounting for multiple testing or conducting meta-analysis. However, the most strongly associated SNP, rs879471, was found to be in linkage disequilibrium with a previously identified risk SNP, rs6010620, in RTEL1. We estimate rs6010620 to account for a glioma incidence rate ratio of 1.34 for Whites relative to East Asians. Conclusion: We explored genetic susceptibility to glioma using a novel candidate SNP method which may be applicable to other diseases with appropriate epidemiologic patterns

Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222.

Background: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. Methods: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. Results: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P = 6.86 x 10(-24), minor allele frequency similar to 0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non- GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. Conclusion: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma