Screening for prostate cancer in New Zealand general practice.

Objective: To ascertain the rates and patterns of prostate-specific antigen (PSA) screening in New Zealand men.

Methods: The study population included 35,958 men aged 40+ years, with no prior diagnosis of prostate cancer, enrolled in 31 general practices in the Midland Cancer Network Region of New Zealand in 2010. Computerized practice records were searched for information, including reasons for testing, for men with elevated PSA test results in 2010.

Surfactant and varespladib co-administration in stimulated rat alveolar macrophages culture.

Acute lung injury is a life-threatening condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity.

Gene expression drives local adaptation in humans.

The molecular basis of adaptation--and, in particular, the relative roles of protein-coding versus gene expression changes--has long been the subject of speculation and debate. Recently, the genotyping of diverse human populations has led to the identification of many putative "local adaptations" that differ between populations. Here I show that these local adaptations are over 10-fold more likely to affect gene expression than amino acid sequence.

Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.

Objectives: This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.

Human chorionic gonadotropin controls luteal vascular permeability via vascular endothelial growth factor by down-regulation of a cascade of adhesion proteins.

Objective: To study the functional interactions of junctional proteins acting as regulators of vascular permeability in the human corpus luteum. We investigated the role of vascular endothelial (VE)-cadherin, nectin 2, and claudin 5 as controllers of vascular endothelial cell permeability.

Design: Performing immunohistochemical dual staining, we colocalized the above-mentioned proteins in the human corpus luteum.

Impact of periodontitis on oral health-related quality of life.

Objectives: To investigate the impact of chronic periodontitis on oral health-related quality of life (OHRQoL) using the full version of the Oral Health Impact Profile (OHIP-49) and the Oral Health Quality of Life-UK (OHQoL-UK) questionnaires.

Methods: 89 patients with chronic periodontitis and 89 age- and gender-matched patients without chronic periodontitis were recruited. OHIP-49 and OHQoL-UK were self-completed by participants and mean scores were calculated for each item, domain and the overall summary score (additive method) for each instrument in each group.

Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression.

Background: Phenotypic evolution in animals is thought to be driven in large part by differences in gene expression patterns, which can result from sequence changes in cis-regulatory elements (cis-changes) or from changes in the expression pattern or function of transcription factors (trans-changes). While isolated examples of trans-changes have been identified, the scale of their overall contribution to regulatory and phenotypic evolution remains unclear.

Results: Here, we attempt to examine the prevalence of trans-effects and their potential impact on gene expression patterns in vertebrate evolution by comparing the function of identical human tissue-specific enhancer sequences in two highly divergent vertebrate model systems, mouse and zebrafish.

Adaptation of a web-based, open source electronic medical record system platform to support a large study of tuberculosis epidemiology.

Background: In 2006, we were funded by the US National Institutes of Health to implement a study of tuberculosis epidemiology in Peru. The study required a secure information system to manage data from a target goal of 16,000 subjects who needed to be followed for at least one year. With previous experience in the development and deployment of web-based medical record systems for TB treatment in Peru, we chose to use the OpenMRS open source electronic medical record system platform to develop the study information system.

Factors underlying variable DNA methylation in a human community cohort.

Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations.

Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies.

Contrast imaging ultrasound detects abnormalities in the marmoset ovary.

The development of a functional vascular tree within the primate ovary is critical for reproductive health. To determine the efficacy of contrast agents to image the microvascular environment within the primate ovary, contrast ultrasonography was performed in six reproductive-aged female common marmosets (Callithrix jacchus) during the late luteal phase of the cycle, following injection of Sonovue™. Regions of interest (ROIs), representing the corpus luteum (CL) and noncorpus luteum ovarian tissue (NCLOT), were selected during gray-scale B-mode ultrasound imaging.

Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints.

The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g.

Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity.

The acquisition of new genes, via horizontal transfer or gene duplication/diversification, has been the dominant mechanism thus far implicated in the evolution of microbial pathogenicity. In contrast, the role of many other modes of evolution--such as changes in gene expression regulation-remains unknown. A transition to a pathogenic lifestyle has recently taken place in some lineages of the budding yeast Saccharomyces cerevisiae.

Impacts of e-health on the outcomes of care in low- and middle-income countries: where do we go from here?

E-health encompasses a diverse set of informatics tools that have been designed to improve public health and health care. Little information is available on the impacts of e-health programmes, particularly in low- and middle-income countries. We therefore conducted a scoping review of the published and non-published literature to identify data on the effects of e-health on health outcomes and costs.

Population-specificity of human DNA methylation.

Background: Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are largely unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated.

Results: Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population.

Ovarian VEGF(165)b expression regulates follicular development, corpus luteum function and fertility.

Angiogenesis and vascular regression are critical for the female ovulatory cycle. They enable progression and regression of follicular development, and corpora lutea formation and regression. Angiogenesis in the ovary occurs under the control of the vascular endothelial growth factor-A (VEGFA) family of proteins, which are generated as both pro-(VEGF(165)) and anti(VEGF(165)b)-angiogenic isoforms by alternative splicing.

Building the foundations of an informatics agenda for global health - 2011 workshop report.

Strengthening the capacity of public health systems to protect and promote the health of the global population continues to be essential in an increasingly connected world. Informatics practices and principles can play an important role for improving global health response capacity. A critical step is to develop an informatics agenda for global health so that efforts can be prioritized and important global health issues addressed.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

Background: The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions.

Secondary prevention of stroke and transient ischaemic attack.

Transient ischaemic attack (TIA) and stroke are clinical syndromes characterised by acute neurological deficits with vascular causes. People experiencing TIA or a first stroke are at significant risk of subsequent stroke. Risk factors have been identified and include factors associated with lifestyle such as tobacco use, diet, obesity, alcohol consumption, physical activity and stress.

A survey of community exercise programmes for stroke survivors in Scotland.

Stroke is the most common cause of complex disability in the community. Physical fitness is often reduced after stroke, but training can improve fitness and function. UK and international stroke clinical guidelines recommend long-term exercise participation for stroke survivors.

Anti-inflammatory effects of varespladib methyl in diabetic patients with acute coronary syndrome.

Purpose: Secretory phospholipase A(2) group IIA (sPLA(2-)IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA(2)-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA(2) inhibition.

Methods: The effects of the sPLA(2) inhibitor varespladib methyl 500 mg daily and placebo on serial changes in inflammatory and lipid biomarkers were examined in 624 ACS patients who were treated with standard of care including atorvastatin 80 mg daily.

Improving the patient experience through design.

Toronto's Princess Margaret Hospital (PMH) received a major financial gift to redesign its chemotherapy daycare and transfusion facilities, which were over capacity and in need of improvement, both functionally and aesthetically. PMH's vision was to create a new space and experience that was truly patient centric and world class. Meanwhile, a research team at the University of Toronto's Rotman School of Management had also received a gift from a corporate donor with a patient-focused mandate to examine ways in which healthcare in Canada could be made more patient centric.

Novel mixed-mode phase transition involving a composition-dependent displacive component.

Solid-solid displacive, structural phase transformations typically undergo a discrete structural change from a parent to a product phase. Coupling electron microscopy, three-dimensional atom probe, and first-principles computations, we present the first direct evidence of a novel mechanism for a coupled diffusional-displacive transformation in titanium-molybdenum alloys wherein the displacive component in the product phase changes continuously with changing composition. These results have implications for other transformations and cannot be explained by conventional theories.