Glial cell morphological and density changes through the lifespan of rhesus macaques.

How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging.

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study.

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation and generate testable predictions.

Persistent microbial dysbiosis in preterm premature rupture of membranes from onset until delivery.

Background. Preterm Premature Rupture of Membranes (PPROM) is a major leading cause of preterm births. While the cause for PPROM remains unidentified, it is anticipated to be due to subclinical infection, since a large proportion of PPROM patients display signs of chorioamnionitis.

A comparison of outcomes between laparoscopic and open appendectomy in Canada.

The benefit of a laparoscopic approach to appendectomy continues to be debated. We compared laparoscopic (LA) with open appendectomy (OA) for appendicitis in Canada using the Canadian Institute for Health Information database (2004-2008). The odds of female patients undergoing LA were 1.

Cellular population dynamics control the robustness of the stem cell niche.

Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain 'stemness' through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche.

Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer: A Multicenter Study.

Background: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective multicenter study involving 5 Canadian cancer centers.

Patients And Methods: Cancer registries identified consecutive patients with locally advanced rectal adenocarcinoma from the Tom Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency, Ottawa Hospital Cancer Centre, and the Dr H.

Bowel obstructions and incisional hernias following trauma laparotomy and the nonoperative therapy of solid organ injuries: A retrospective population-based analysis.

Background: Small bowel obstruction (SBO) and incisional hernia (IH) represent the most common long-term complications of laparotomy. They may also be more common among injured patients than for elective/nontrauma emergency scenarios. Unfortunately, the population-based incidence of SBO and IH following trauma laparotomy is unknown.

Prevalence of eating disorders in males: a review of rates reported in academic research and UK mass media.

Media presentations of health issues affect evaluations of personal susceptibility to particular illnesses and hence help-seeking behaviours. We examined data on prevalence of eating disorders (EDs - which are often characterised as 'female') among males in: scientific literature; readily-accessible web-based information; and UK newspaper articles (published 7/12/2002-7/12/2012). This revealed conflicting statistics.

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.

Background: Studies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database.

Patients And Methods: Data for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers.

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model.

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.

Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK.

Ulna Nerve Decompression at the Elbow in Patients with Normal Nerve Conduction Tests.

Background: Ulna nerve compression at the elbow is the second most common neuropathy of the upper limb. It has been suggested that nerve conduction tests are required to correctly make the diagnosis. The aim of this study was to assess whether patients with normal nerve conduction testing benefitted from surgical release of the ulna nerve.

"It's not healthy and it's decidedly not masculine": a media analysis of UK newspaper representations of eating disorders in males.

Objectives: Recent qualitative research found young men reporting that an expectation that eating disorders (EDs) mainly affect young women led them, and others, to only recognise their symptoms when their ED had become entrenched. This raises questions about how these stereotypes persist. We therefore explored how EDs in males were represented in articles published in UK newspapers over a 10-year period (7.

Hospital volume and other risk factors for in-hospital mortality among diverticulitis patients: A nationwide analysis.

Background: Previous studies have found that a higher volume of colorectal surgery was associated with lower mortality rates. While diverticulitis is an increasingly common condition, the effect of hospital volume on outcomes among diverticulitis patients is unknown.

Objective: To evaluate the relationship between hospital volume and other factors on in-hospital mortality among patients admitted for diverticulitis.

New advances on glial activation in health and disease.

In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development.

Colonic perforation with intraluminal stents and bevacizumab in advanced colorectal cancer: retrospective case series and literature review.

Background: Self-expanding metal stents (SEMS) are increasingly used in the treatment of malignant large bowel obstruction in the setting of inoperable colorectal cancer. Perforation is a well-known complication associated with these devices. The addition of the vascular endothelial growth factor inhibitor bevacizumab is suspected to increase the rate, but the extent of the increase is not known.

Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort.

Background: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment.

Objectives: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing.

Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control.

Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM) may alter lipid levels and may alter the efficacy of lipid-modifying agents.

Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT) in subgroups of patients with T2DM with better or poorer glycemic control.

Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796), examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels.

Parameter-free methods distinguish Wnt pathway models and guide design of experiments.

The canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localization; our aim is to distinguish between the models and distill biological insight from them. Using Bayesian methods we infer parameters for each model from mammalian Wnt signaling data and find that all models can fit this time course.