No evidence of disease activity: indirect comparisons of oral therapies for the treatment of relapsing-remitting multiple sclerosis.

Introduction: No head-to-head trials have compared the efficacy of the oral therapies, fingolimod, dimethyl fumarate and teriflunomide, in multiple sclerosis. Statistical modeling approaches, which control for differences in patient characteristics, can improve indirect comparisons of the efficacy of these therapies.

Methods: No evidence of disease activity (NEDA) was evaluated as the proportion of patients free from relapses and 3-month confirmed disability progression (clinical composite), free from gadolinium-enhancing T1 lesions and new or newly enlarged T2 lesions (magnetic resonance imaging composite), or free from all disease measures (overall composite).

Occupational allergic contact dermatitis to chromium from cement: Estimating the size of the problem in Australia.

Background: Allergic contact dermatitis (ACD) caused by chromium in cement is a significant occupational hazard. However, legislation in Europe over the past two decades to reduce the concentration of chromium in cement to <2 ppm through the addition of ferrous sulphate to cement, has seen a significant decrease in the incidence of chromium allergy. No such legislation exists in Australia.

2014 Report on the Milestones for the US National Plan to Address Alzheimer's Disease.

With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025.

Polymer fluctuation lubrication in hydrogel gemini interfaces.

Interfacial sliding speed and contact pressure between the sub-units of particulate soft matter assemblies can vary dramatically across systems and with dynamic conditions. By extension, frictional interactions between particles may play a key role in their assembly, global configuration, collective motion, and bulk material properties. For example, in tightly packed assemblies of microgels - colloidal microspheres made of hydrogel - particle stiffness controls the fragility of the glassy state formed by the particles.

Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits.

Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer's disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes.

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases.

The first Australian Baseline Series: Recommendations for patch testing in suspected contact dermatitis.

Background And Objectives: Patch testing is a standard diagnostic tool used in the identification of causative allergens in allergic contact dermatitis. Ongoing surveillance of rates of allergen positivity is vitally important to detect trends and allow comparisons between countries. The objective of this study was to propose the first evidence-based Australian baseline series, based on retrospective review of our patch test data.

Spared piriform cortical single-unit odor processing and odor discrimination in the Tg2576 mouse model of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest reported signs of Alzheimer's disease is olfactory dysfunction, which may manifest in a variety of ways. The present study sought to address this issue by investigating odor coding in the anterior piriform cortex, the primary cortical region involved in higher order olfactory function, and how it relates to performance on olfactory behavioral tasks.

Unsuspected allergic contact dermatitis to alcohol swabs following neurosurgery.

We report a case of a 12-year-old girl with severe allergic contact dermatitis following neurosurgery secondary to topical use of isopropyl alcohol swabs. Alcohol swabs should not be overlooked as potential allergens. In our case, it was initially assumed that the cause of her reaction was either tapes or topical local anaesthetic.

Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary glia from a mouse model of Alzheimer's disease.

Defective autophagy in Alzheimer's disease (AD) promotes disease progression in diverse ways. Here, we demonstrate impaired autophagy flux in primary glial cells derived from CRND8 mice that overexpress mutant amyloid precursor protein (APP). Functionalized single-walled carbon nanotubes (SWNT) restored normal autophagy by reversing abnormal activation of mTOR signaling and deficits in lysosomal proteolysis, thereby facilitating elimination of autophagic substrates.

Positive patch test reactions to oxidized limonene: exposure and relevance.

Background: R-Limonene is a common fragrance terpene found in domestic and industrial products. R-Limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a recent multicentre study, 5.

Benefit-risk assessment in a post-market setting: a case study integrating real-life experience into benefit-risk methodology.

Purpose: Difficulties may be encountered when undertaking a benefit-risk assessment for an older product with well-established use but with a benefit-risk balance that may have changed over time. This case study investigates this specific situation by applying a formal benefit-risk framework to assess the benefit-risk balance of warfarin for primary prevention of patients with atrial fibrillation.

Methods: We used the qualitative framework BRAT as the starting point of the benefit-risk analysis, bringing together the relevant available evidence.

Specific calpain inhibition by calpastatin prevents tauopathy and neurodegeneration and restores normal lifespan in tau P301L mice.

Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5.

A review of overgeneral memory in child psychopathology.

Objectives: Overgeneral autobiographical memory (OGM) refers to the impaired retrieval of specific events from autobiographical memory. This review examined OGM in children and adolescents to answer three main questions. First, do children demonstrate OGM? Second, how does the experience of OGM relate to childhood trauma and associated psychopathology? Third, is the CaR-FA-X model (Williams et al.

Variations in the quality and sustainability of long-term glycaemic control with continuous subcutaneous insulin infusion.

Aims: To investigate the pattern of changes in HbA1c in people with Type 1 diabetes managed by long-term Continuous subcutaneous insulin infusion.

Methods: We studied HbA1c changes using computerized clinic records in 35 adult people with Type 1 diabetes and an elevated HbA1c (≥ 64 mmol/mol, 8.0%) on multiple daily insulin injections, who were then switched to continuous subcutaneous insulin infusion for at least 5 years.

Polysensitisation in a laboratory scientist associated with allergic contact dermatitis from methylisothiazolinone in skin cleansers.

Polysensitisation refers to reactivity to three or more allergens on epicutaneous patch testing, and is likely to affect a distinct subgroup of individuals with allergic contact dermatitis (ACD). Methylisothiazolinone (MIT) is an increasingly prevalent allergen, recently having been described as occurring in epidemic proportions. We report a patient with ACD to 12 allergens, including MIT, and discuss the implications of polysensitisation and the likely need for repeat patch testing in such patients if they subsequently re-present with dermatitis.

Overexpression of the calpain-specific inhibitor calpastatin reduces human alpha-Synuclein processing, aggregation and synaptic impairment in [A30P]αSyn transgenic mice.

Lewy bodies, a pathological hallmark of Parkinson's disease (PD), contain aggregated alpha-synuclein (αSyn), which is found in several modified forms and can be discovered phosphorylated, ubiquitinated and truncated. Aggregation-prone truncated species of αSyn caused by aberrant cleavage of this fibrillogenic protein are hypothesized to participate in its sequestration into inclusions subsequently leading to synaptic dysfunction and neuronal death. Here, we investigated the role of calpain cleavage of αSyn in vivo by generating two opposing mouse models.

Comorbidity in the prediction of Cognitive Processing Therapy treatment outcomes for combat-related posttraumatic stress disorder.

This paper examines clinical predictors of posttraumatic stress disorder (PTSD) treatment outcomes following Cognitive Processing Therapy (CPT) in Australian military veterans. Fifty nine treatment seeking veterans were enrolled in a randomized controlled trial comparing 12 sessions of CPT (n = 30) with usual treatment (n = 29) at three community-based veterans counseling centers. PTSD and key co-morbidities (depression, anxiety, anger and alcohol use) were measured.

Suspected allergic contact dermatitis to iodopropynyl butylcarbamate in an alcohol hand rub commonly used in Australian health-care settings.

We report a case of suspected allergic contact dermatitis to the preservative and uncommon allergen iodopropynyl butylcarbamate, found in Microshield Angel hand gel, a skin cleanser commonly used in Australian health-care settings.

Multilevel models for cost-effectiveness analyses that use cluster randomised trial data: An approach to model choice.

Multilevel models provide a flexible modelling framework for cost-effectiveness analyses that use cluster randomised trial data. However, there is a lack of guidance on how to choose the most appropriate multilevel models. This paper illustrates an approach for deciding what level of model complexity is warranted; in particular how best to accommodate complex variance-covariance structures, right-skewed costs and missing data.