A gene-family analysis of 61 genetic variants in the nicotinic acetylcholine receptor genes for insulin resistance and type 2 diabetes in American Indians.

Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with smoking phenotypes and are likely to influence diabetes. Although each single variant may have only a minor effect, the joint contribution of multiple single nucleotide polymorphisms (SNPs) to the occurrence of disease may be larger.

The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease.

Objectives: Fecal calprotectin (FC) is elevated in patients with inflammatory bowel disease (IBD). Studies evaluating FC during the initial investigation of children with suspected IBD have been limited, especially with regard to their small patient groups. We aimed to evaluate the diagnostic accuracy of FC in a large regional cohort of children undergoing full upper and lower endoscopy for suspected IBD, comparing FC with six common blood parameters.

The surgical management of H-type rectovestibular fistula: a case report and brief review of the literature.

H-type rectovestibular fistula is a rare anorectal malformation with poor consensus on an optimal operative management. We report our management of a recurrent fistula and review previously described operative techniques. Full excision of the tract without apposing suture lines or perineal body dissection simplifies the repair while minimizing complications and recurrence risk.

Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers.

Pre-clinical studies suggest that the neurokinin-1 (NK1) receptor may modulate the response to opioids, with NK(1) inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK1 antagonist currently marketed for clinical use as an anti-emetic. This 6-week in-patient study used a randomized, double-blind, double-dummy, within-subject, crossover design.

The role of autophagy in Crohn's disease.

(Macro)-autophagy is a homeostatic process by which eukaryotic cells dispose of protein aggregates and damaged organelles. Autophagy is also used to degrade micro-organisms that invade intracellularly in a process termed xenophagy. Genome-wide association scans have recently identified autophagy genes as conferring susceptibility to Crohn's disease (CD), one of the chronic inflammatory bowel diseases, with evidence suggesting that CD arises from a defective innate immune response to enteric bacteria.

Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells.

Unlabelled: Peptides featuring the LR(S/T) motif were identified that could specifically bind to the C-type lectin-like molecule-1 (CLL1), a protein preferentially expressed on acute myeloid leukemia stem cells (LSCs). Micellar nanoparticles were covalently decorated with CLL1-targeting peptides for targeted drug delivery. The resulting peptide-coated nanoparticles were 13.

Mathematical modeling and frequency gradient analysis of cellular and vascular invasion into integra and strattice: toward optimal design of tissue regeneration scaffolds.

Background: Rapid, effective host cell invasion and vascularization is essential for durable incorporation of avascular tissue-replacement scaffolds. In this study, the authors sought to qualitatively and quantitatively determine which of two commercially available products (i.e.

Changes in perceived pain severity following interdisciplinary treatment for chronic pain.

Background: There is good support for the effectiveness of interdisciplinary chronic pain management programs in improving functional outcomes; however, relatively little is known about patients who report deterioration following participation in such programs.

Objectives: The present retrospective study investigated patients' reports of increased pain severity during participation in a cognitive-behaviourally oriented, outpatient treatment for chronic pain.

Methods: Participants (n=280) completed a four-week, group-based, interdisciplinary chronic pain self-management program at a rehabilitation hospital.

An interdisciplinary approach to the prevention and treatment of groin wound complications after lower extremity revascularization.

Background: If not effectively treated, groin wound infections following lower extremity revascularization (LER) may result in graft or limb loss.

Methods: A retrospective review was performed of all patients who underwent muscle flap transposition by a single surgeon after LER between 2006 and 2010.

Results: Twenty-nine muscle transposition flaps were performed in 24 patients (21 sartorius, 6 rectus femoris, and 2 gracilis).

Genome-wide methylation profiling in Crohn's disease identifies altered epigenetic regulation of key host defense mechanisms including the Th17 pathway.

Background: Germline variation in the 71 Crohn's disease (CD) loci implicated by genome-wide association studies (GWAS) only accounts for approximately 25% of estimated heritability. The contribution of epigenetic alterations to disease pathogenesis is emerging as a research priority.

Materials And Methods: The methylation status of 27,578 CpG sites across the genome was analyzed using the Illumina Human Methylation27 assay in DNA extracted from whole blood samples from 40 adult females (21 ileal CD, 19 healthy controls) and 16 girls with childhood-onset CD, all nonsmokers.

Microstructured templates for directed growth and vascularization of soft tissue in vivo.

Tissue templates for reconstruction and regeneration in vivo have achieved clinical successes for homogeneous tissues in well vascularized regions. Outstanding challenges exist for applications in poorly vascularized regions and for spatially differentiated tissues. Here, we present a strategy to control the spatial patterns of cell and vascular ingrowth throughout the volume of a bioremodelable and resorbable matrix via well-defined micropores and networks of microchannels.

Stromal-derived factor-1 delivered via hydrogel drug-delivery vehicle accelerates wound healing in vivo.

Topical treatment of superficial wounds has many advantages including decreased cost and increased ease of application compared with systemic treatments. Many of the advantages, however, are lost when it is necessary for repeated doses of topical medications to be given over an extended period of time. Therefore, a drug-delivery vehicle that delivers biologically appropriate doses in a sustained fashion would prove valuable.

Overcoming barriers to membrane protein structure determination.

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Alcohol screening scores and the risk of new-onset gastrointestinal illness or related hospitalization.

Background: Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis.

Objective: To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores.

Design: Retrospective cohort study.

Determinants of ligand binding affinity and cooperativity at the GLUT1 endofacial site.

Cytochalasin B (CB) and forskolin (FSK) inhibit GLUT1-mediated sugar transport in red cells by binding at or close to the GLUT1 endofacial sugar binding site. Paradoxically, very low concentrations of each of these inhibitors produce a modest stimulation of sugar transport [ Cloherty, E. K.

Diagnosing irritable bowel syndrome: a changing clinical paradigm.

Rather than being a diagnosis of exclusion, irritable bowel syndrome (IBS) is a diagnosis that can be identified by symptom-based criteria. The collection of these criteria by a meticulous history can be enhanced by using various tools. Once a positive diagnosis is made, using clinical criteria for diagnosis, one should look for alarm or warning symptoms or signs, and should characterize the type of bowel habit.

Characterizing diffusion dynamics of a membrane protein associated with nanolipoproteins using fluorescence correlation spectroscopy.

Nanolipoprotein particles (NLPs) represent a unique nanometer-sized scaffold for supporting membrane proteins (MP). Characterization of their dynamic shape and association with MP in solution remains a challenge. Here, we present a rapid method of analysis by fluorescence correlation spectroscopy (FCS) to characterize bacteriorhodopsin (bR), a membrane protein capable of forming a NLP complex.