Impact of Scotland’s comprehensive, smoke-free legislation on stroke

<p>Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.</p> <p>Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.</p> <p>Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.</p&gt

Genome-Wide Identification of Bcl11b Gene Targets Reveals Role in Brain-Derived Neurotrophic Factor Signaling

B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells

What the radiologist needs to know about the diabetic patient

Diabetes mellitus (DM) is recognised as a major health problem. Ninety-nine percent of diabetics suffer from type 2 DM and 10% from type 1 and other types of DM. The number of diabetic patients worldwide is expected to reach 380 millions over the next 15 years. The duration of diabetes is an important factor in the pathogenesis of complications, but other factors frequently coexisting with type 2 DM, such as hypertension, obesity and dyslipidaemia, also contribute to the development of diabetic angiopathy. Microvascular complications include retinopathy, nephropathy and neuropathy. Macroangiopathy mainly affects coronary arteries, carotid arteries and arteries of the lower extremities. Eighty percent of deaths in the diabetic population result from cardiovascular incidents. DM is considered an equivalent of coronary heart disease (CHD). Stroke and peripheral artery disease (PAD) are other main manifestations of diabetic macroangiopathy. Diabetic cardiomyopathy (DC) represents another chronic complication that occurs independently of CHD and hypertension. The greater susceptibility of diabetic patients to infections completes the spectrum of the main consequences of DM. The serious complications of DM make it essential for physicians to be aware of the screening guidelines, allowing for earlier patient diagnosis and treatment

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology

A Cu(I) coordination polymer employing a nonsteroidal aromatase inhibitor letrozole as a building block

The reaction of [Cu(I)(MeCN) 4](BF 4) with letrozole (1-[bis(4-cyanophenyl)methyl]-1,2,4-triazole, LTZ) affords a quite unusual 3-D coordination polymer in which for the first time LTZ demonstrates its coordinating ability as a tetradentate ligand.link_to_subscribed_fulltex

A favorable tumor size to define papillary thyroid microcarcinoma: an analysis of 1176 consecutive cases

Yanping Gong, Genpeng Li, Jianyong Lei, Jiaying You, Ke Jiang, Zhihui Li, Rixiang Gong, Jingqiang Zhu Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China Background: The optimal treatment strategy for papillary thyroid microcarcinoma (PTMC) has remained controversial. The purpose of this study was to provide a new reference value for PTMC to aid the selection of optimal management for minute lesions.Patients and methods: A pool of 1176 consecutive patients who met the inclusion criteria were ultimately enrolled in this study. The correlation of papillary thyroid carcinoma (PTC) tumor size and lymph node metastasis was analyzed. Receiver operating characteristic curve studies were conducted to identify the reference value by determining the optimal cut-off point of size related to lymph node metastasis. To validate our results, all selected patients were divided into two groups according to the cut-off point and some of the prognostic factors were compared.Results: A moderate significant correlation was found between the tumor size and the average number of lymph node metastases (r=0.502, P<0.01) and the percentage of lymph node metastasis (r=0.625, P<0.01). The optimal cut-off reference value was 8.5 mm according to the receiver operating characteristic curves. Significant differences were observed for PTC prognostic factors, for example, extrathyroidal extension, multifocality, pathologic (p) N+ stage, occult metastasis in clinical (c) N− stage, radioactive iodine ablation, and recurrence between the two groups.Conclusion: Due to more aggressive behavior and poorer prognosis in larger tumor size (>8.5 mm), a tumor size ≤8.5 mm in diameter may be favorable to discriminate PTMC from PTC and aid the selection of optimal management. Keywords: thyroid neoplasms, carcinoma, papillary, lymph nodes&nbsp