The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 () and confers an increased risk for several autoimmune diseases, including T1D.

The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 ( ), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1 ) and confers an increased risk for several autoimmune diseases, including T1D.

Pediatric Distraction Tools for Prehospital Care of Pain and Distress: A Systematic Review.

Context: Distraction therapies are widely used in emergency departments to manage pediatric pain and distress. Little is known about which distraction techniques would translate best into the prehospital environment.

Objective: To identify emergency department-based distraction techniques for managing pain and/or distress in pediatric patients who may be suitable for the prehospital environment.

Aberrant expression and localization of the RAP1 shelterin protein contribute to age-related phenotypes.

Short telomeres induce a DNA damage response (DDR) that evokes apoptosis and senescence in human cells. An extant question is the contribution of telomere dysfunction-induced DDR to the phenotypes observed in aging and telomere biology disorders. One candidate is RAP1, a telomere-associated protein that also controls transcription at extratelomeric regions.

NAD-Linked Metabolism and Intervention in Short Telomere Syndromes and Murine Models of Telomere Dysfunction.

Telomeres are specialized nucleoprotein structures that form protective caps at the ends of chromosomes. Short telomeres are a hallmark of aging and a principal defining feature of short telomere syndromes, including dyskeratosis congenita (DC). Emerging evidence suggests a crucial role for critically short telomere-induced DNA damage signaling and mitochondrial dysfunction in cellular dysfunction in DC.

Re-equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction.

Short telomeres are a principal defining feature of telomere biology disorders, such as dyskeratosis congenita (DC), for which there are no effective treatments. Here, we report that primary fibroblasts from DC patients and late generation telomerase knockout mice display lower nicotinamide adenine dinucleotide (NAD) levels, and an imbalance in the NAD metabolome that includes elevated CD38 NADase and reduced poly(ADP-ribose) polymerase and SIRT1 activities, respectively, affecting many associated biological pathways. Supplementation with the NAD precursor, nicotinamide riboside, and CD38 inhibition improved NAD homeostasis, thereby alleviating telomere damage, defective mitochondrial biosynthesis and clearance, cell growth retardation, and cellular senescence of DC fibroblasts.

Antimicrobial Peptides Derived from the Immune Defense Protein CAP37 Inhibit TLR4 Activation by S100A9.

Purpose: Corneal abrasion is a common eye injury, and its resolution can be seriously complicated by bacterial infection. We showed that topical application of the cationic antimicrobial protein of 37 kDa (CAP37) promotes corneal re-epithelialization in mice, and peptides derived from CAP37 can recapitulate the antibacterial and wound-healing effects of the full-length protein. The current study was designed to identify the molecular mechanisms mediating the wound-healing effect of CAP37 and derived bioactive peptides.

The enigma of excessively long telomeres in cancer: lessons learned from rare human POT1 variants.

The discovery that rare POT1 variants are associated with extremely long telomeres and increased cancer predisposition has provided a framework to revisit the relationship between telomere length and cancer development. Telomere shortening is linked with increased risk for cancer. However, over the past decade, there is increasing evidence to show that extremely long telomeres caused by mutations in shelterin components (POT1, TPP1, and RAP1) also display an increased risk of cancer.

Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

Objective: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice.

Study Design: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals.

The role of neutrophil granule proteins in neuroinflammation and Alzheimer's disease.

Neutrophils are the innate immune system's first line of defense. Neutrophils play a critical role in protecting the host against infectious pathogens, resolving sterile injuries, and mediating inflammatory responses. The granules of neutrophils and their constituent proteins are central to these functions.

The Role of Neutrophil Proteins on the Amyloid Beta-RAGE Axis.

We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer's disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression.

Walk them or no leg to stand on! Diagnostic delay of neurologic conditions in young children.

Diagnosis of low incidence neurological conditions can be a challenge in paediatric emergency medicine. Neurological examination in young children can be very difficult, and medical staff may not previously have encountered conditions like acute demyelinating encephalomyelitis. We propose that the simple process of walking a child (provided they were previously ambulant) is the crucial step in the neurological examination.

Water availability as an agent of selection in introduced populations of Arabidopsis thaliana: impacts on flowering time evolution.

Flowering is one of the most influential events in the life history of a plant and one of the main determinants of reproductive investment and lifetime fitness. It is also a highly complex trait controlled by dozens of genes. Understanding the selective pressures influencing time to flowering, and being able to reliably predict how it will evolve in novel environments, are unsolved challenges for plant evolutionary geneticists.

Quantitative genetic variance and multivariate clines in the Ivyleaf morning glory, Ipomoea hederacea.

Clinal variation is commonly interpreted as evidence of adaptive differentiation, although clines can also be produced by stochastic forces. Understanding whether clines are adaptive therefore requires comparing clinal variation to background patterns of genetic differentiation at presumably neutral markers. Although this approach has frequently been applied to single traits at a time, we have comparatively fewer examples of how multiple correlated traits vary clinally.

Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial.

Objective: To determine whether the probiotic Lactobacillus reuteri DSM 17938 reduces crying or fussing in a broad community based sample of breastfed infants and formula fed infants with colic aged less than 3 months.

Design: Double blind, placebo controlled randomised trial.

Setting: Community based sample (primary and secondary level care centres) in Melbourne, Australia.

Success rate of BladderScan-assisted suprapubic aspiration.

Objective: Suprapubic aspiration (SPA) is the gold standard for obtaining uncontaminated urine specimens in young febrile children. The use of real-time ultrasound (RTUS) has been shown to increase the success rate of SPA. The BladderScan (BSUS) Verathon(®) is an alternative portable ultrasound device designed to provide automated measurement of bladder volume.

Practical communication guide for paediatric procedures.

Children undergo many diagnostic and therapeutic procedures in the ED. Although emergency staff can often intervene to reduce physical pain through topical anaesthesia, analgesia and sedation, much procedural distress can be addressed by better preparing patients and families for the procedures. A key to guiding children through procedures is the use of age-appropriate and non-threatening language by all clinicians involved.

Postnatal depression in mothers bringing infants to the emergency department.

Objective: To determine the prevalence of postnatal depression (PND) in mothers of young infants presenting to the emergency department (ED).

Design, Setting And Participants: Prospective observational study of the prevalence of PND in mothers of infants aged 14 days to 6 months presenting with non-time-critical conditions to the ED of a large tertiary paediatric hospital.

Main Outcome Measures: We assessed PND by applying a self-administered validated screening tool, the Edinburgh Postnatal Depression Scale (EPDS).

Probiotics to improve outcomes of colic in the community: protocol for the Baby Biotics randomised controlled trial.

Background: Infant colic, characterised by excessive crying/fussing for no apparent cause, affects up to 20% of infants under three months of age and is a great burden to families, health professionals and the health system. One promising approach to improving its management is the use of oral probiotics. The Baby Biotics trial aims to determine whether the probiotic Lactobacillus reuteri DSM 17938 is effective in reducing crying in infants less than three months old (<13.

Assessing bladder volumes in young children prior to instrumentation: accuracy of an automated ultrasound device compared to real-time ultrasound.

Objectives: Automated bladder ultrasound (ABUS) devices are portable and designed to provide automated measurement of bladder volume. They are simple and require minimal training compared to conventional real-time ultrasound (RTUS). Their most common application in the acute pediatric setting is to assess bladder volumes prior to performing invasive urine collection such as suprapubic aspiration (SPA) in children younger than 2 years of age.

Confirming nasogastric tube position in the emergency department: pH testing is reliable.

Objective: The aim of this study was to determine whether pH testing is an accurate method of confirming nasogastric tube (NGT) position in children with and without gastroenteritis in the emergency department.

Methodology: A prospective observational study of NGT insertions was conducted at a tertiary pediatric emergency department, during a 9-month period in 2006. We evaluated methods of NGT position confirmation, pH of nasogastric aspirates from patients with and without gastroenteritis, and adverse events.