An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer.

Background And Aims: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk.

Methods: We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design.

The p-EVES study design and methodology: a randomised controlled trial to compare portable electronic vision enhancement systems (p-EVES) to optical magnifiers for near vision activities in visual impairment.

Purpose: To describe the study design and methodology for the p-EVES study, a trial designed to determine the effectiveness, cost-effectiveness and acceptability of portable Electronic Vision Enhancement System (p-EVES) devices and conventional optical low vision aids (LVAs) for near tasks in people with low vision.

Methods: The p-EVES study is a prospective two-arm randomised cross-over trial to test the hypothesis that, in comparison to optical LVAs, p-EVES can be: used for longer duration; used for a wider range of tasks than a single optical LVA and/or enable users to do tasks that they were not able to do with optical LVAs; allow faster performance of instrumental activities of daily living; and allow faster reading. A total of 100 adult participants with visual impairment are currently being recruited from Manchester Royal Eye Hospital and randomised into either Group 1 (receiving the two interventions A and B in the order AB), or Group 2 (receiving the two interventions in the order BA).

New inhibitors of the Kvβ2 subunit from mammalian Kv1 potassium channels.

The role of the redox state of Kvβ subunits in the modulation of Kv1 potassium channels has been well documented over the past few years. It has been suggested that a molecule that binds to or inhibits the aldo-keto reductase activity of Kvβ might affect the modulation of channel properties. Previous studies of possible modulators of channel activity have shown that cortisone and some related compounds are able to physically dissociate the channel components by binding to a site at the interface between α and β subunits.

Formulation strategies to improve oral peptide delivery.

Delivery of peptides by the oral route greatly appeals due to commercial, patient convenience and scientific arguments. While there are over 60 injectable peptides marketed worldwide, and many more in development, most delivery strategies do not yet adequately overcome the barriers to oral delivery. Peptides are sensitive to chemical and enzymatic degradation in the intestine, and are poorly permeable across the intestinal epithelium due to sub-optimal physicochemical properties.

Copper isotope fractionation during equilibration with natural and synthetic ligands.

As copper (Cu) stable isotopes emerge as a tool for tracing Cu biogeochemical cycling, an understanding of how Cu isotopes fractionate during complexation with soluble organic ligands in natural waters and soil solutions is required. A Donnan dialysis technique was employed to assess the isotopic fractionation of Cu during complexation with the soluble synthetic ligands ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), iminodiacetic acid (IDA) and desferrioxamine B (DFOB), as well as with Suwannee River fulvic acid (SRFA). The results indicated enrichment of the heavy isotope ((65)Cu) in the complexes, with Δ(65)Cu complex-free values ranging from +0.

Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases.

Tissue inflammation results in the production of numerous reactive oxygen, nitrogen and chlorine species, in addition to the products of lipid and sugar oxidation. Some of these products are capable of chemically modifying amino acids. This in turn results in changes to the structure and function of proteins.

The use of bedside ultrasound and community-based paracentesis in a palliative care service.

Introduction: There is little information, particularly in New Zealand, on the use of ultrasound to enhance clinical decision-making in a specialist palliative care service. Technological advances have resulted in increasingly portable, user-friendly ultrasound machines that can be used in the home setting to offer convenient access to this treatment option.

Aim: To evaluate the clinical use of portable ultrasonography in the management of abdominal ascites in a community palliative care service.

Autoantibodies to posttranslational modifications in rheumatoid arthritis.

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described.

Models of low vision care: past, present and future.

Over the last 50 years, the concept of a low vision service has changed considerably. It has moved away from just the optometrist or optician dispensing magnifiers, to having a large team working across the health and social/ community care sectors, with voluntary organisations often playing an important role. This paper reviews how low vision rehabilitation services have evolved and what models of low vision care are currently available.

Evidence that the lung Adenocarcinoma EML4-ALK fusion gene is not caused by exposure to secondhand tobacco smoke during childhood.

Background: The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. Meanwhile, never smokers exposed to secondhand tobacco smoke (SHS) during childhood are diagnosed at a younger age compared with never smoking patients with lung cancer who are not exposed. We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene.

AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap.

Framework for handling asbestos after a tidal surge.

The tidal surge associated with Tropical Cyclone Yasi--a category 5 system--on February 3, 2011, culminated in asbestos-containing material (ACM) becoming comingled with soil, sand, vegetation, and other debris in the communities of Tully Heads and Hull Heads in Queensland, Australia. The situation was a major concern and the area was deemed by the Queensland Government a priority due to the potential public health risk. The immediate challenge was that no agreed-upon operational framework existed between key response organizations for handling ACM after a tidal surge.

Recovery of golfing ability in someone with an incomplete spinal cord injury: a case report.

Purpose: The purpose of this case report was to describe the elements needed to play golf, detail a rehabilitation program designed to teach someone with an incomplete spinal cord injury (SCI) to play golf and to document outcomes of such a program.

Methods: The participant was a 58-year-old male who sustained an incomplete C3-C6 SCI. The program was divided into three phases.

Detection and characterization of autoantibodies against modified self-proteins in SLE sera after exposure to reactive oxygen and nitrogen species.

There are over 120 types of autoantibodies found in the blood of SLE patients against cellular and extracellular components in both their native and posttranslationally modified forms. In recent years, these autoantibodies have provoked interest as initiators of pathology and as biomarkers of disease activity. Often, the host antigens employed in lab-based and commercially developed immunoassays use non-human antigen or non-modified host antigen as a probe for autoantibodies.

Ocular and visual status among children in special schools in Wales: the burden of unrecognised visual impairment.

Background/aims: The high prevalence of visual defects among children with special needs is well reported and guidelines for vision screening are in place. However, recent research has suggested that vision care for such children is neglected. This study set out to evaluate the current status of vision screening and eye care in special schools in Wales.

Asymmetric segregation of template DNA strands in basal-like human breast cancer cell lines.

Background And Methods: Stem or progenitor cells from healthy tissues have the capacity to co-segregate their template DNA strands during mitosis. Here, we set out to test whether breast cancer cell lines also possess the ability to asymmetrically segregate their template DNA strands via non-random chromosome co-segregation, and whether this ability correlates with certain properties attributed to breast cancer stem cells (CSCs). We quantified the frequency of asymmetric segregation of template DNA strands in 12 human breast cancer cell lines, and correlated the frequency to molecular subtype, CD44+/CD24-/lo phenotype, and invasion/migration ability.

Results of a mixed-methods evaluation of partnerships for health: a quality improvement initiative for diabetes care.

Purpose: Quality improvement (QI) initiatives have been implemented to facilitate transition to a chronic disease management approach in primary health care. However, the effect of QI initiatives on diabetes clinical processes and outcomes remains unclear. This article reports the effect of Partnerships for Health, a QI program implemented in Southwestern Ontario, Canada, on diabetes clinical process and outcome measures and describes program participants' views of elements that influenced their ability to reach desired improvements.

α-Synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of Parkinson disease.

Parkinson disease (PD) is a multifactorial disease resulting in preferential death of the dopaminergic neurons in the substantia nigra. Studies of PD-linked genes and toxin-induced models of PD have implicated mitochondrial dysfunction, oxidative stress, and the misfolding and aggregation of α-synuclein (α-syn) as key factors in disease initiation and progression. Many of these features of PD may be modeled in cells or animal models using the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)).

Region-specific deficits in dopamine, but not norepinephrine, signaling in a novel A30P α-synuclein BAC transgenic mouse.

Parkinson's disease (PD) is a neurodegenerative disorder classically characterized by the death of dopamine (DA) neurons in the substantia nigra pars compacta and by intracellular Lewy bodies composed largely of α-synuclein. Approximately 5-10% of PD patients have a familial form of Parkinsonism, including mutations in α-synuclein. To better understand the cell-type specific role of α-synuclein on DA neurotransmission, and the effects of the disease-associated A30P mutation, we generated and studied a novel transgenic model of PD.

Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model.

The pathological end-state of Parkinson disease is well described from postmortem tissue, but there remains a pressing need to define early functional changes to susceptible neurons and circuits. In particular, mechanisms underlying the vulnerability of the dopamine neurons of the substantia nigra pars compacta (SNc) and the importance of protein aggregation in driving the disease process remain to be determined. To better understand the sequence of events occurring in familial and sporadic Parkinson disease, we generated bacterial artificial chromosome transgenic mice (SNCA-OVX) that express wild-type α-synuclein from the complete human SNCA locus at disease-relevant levels and display a transgene expression profile that recapitulates that of endogenous α-synuclein.

The clinical significance of antimicrobial serologic responses within an Irish Crohn's disease population.

Introduction: A hyper-responsive adaptive immunologic response to a variety of microbial antigens has been described in Crohn's disease (CD) patients and elevated levels of a number of antibodies have been identified in the sera of CD patients. To date, the serological profiles of an Irish CD population have not been characterized.

Objectives: The aim of this study is to determine the serological profile of Irish patients with CD.