Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies.

Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA.

Altered energy intake and the amplitude of the body temperature rhythm are associated with changes in phase, but not amplitude, of clock gene expression in the rat suprachiasmatic nucleus in vivo.

Circadian rhythms in mammals are driven by a central clock in the suprachiasmatic nucleus (SCN). In vitro, temperature cycles within the physiological range can act as potent entraining cues for biological clocks. We altered the body temperature (Tc) rhythm in rats by manipulating energy intake (EI) to determine whether EI-induced changes in Tc oscillations are associated with changes in SCN clock gene rhythms in vivo.

Influence of respiratory dead space on lung clearance index in preterm infants.

Lung clearance index (LCI), a marker of ventilation inhomogeneity derived from multiple breath washout (MBW), is used for clinical monitoring and as a key outcome of clinical trials in infants and children with cystic fibrosis. Utility of LCI is controversial in preterm infants with bronchopulmonary dysplasia (BPD) who tend to have high dead space to tidal volume ratio (VD/VT). We investigated the effect of VD/VT on LCI in a cohort of preterm infants with and without BPD and term healthy controls.

Influence of the paraflocculus on normal and abnormal spontaneous firing rates in the inferior colliculus.

Spontaneous firing rates of neurons in the central auditory pathway, such as in the inferior colliculus, are known to be increased after cochlear trauma. This so-called hyperactivity is thought to be involved in the generation of tinnitus, a phantom auditory perception. Recent research in an animal model suggests behavioural signs of tinnitus can be significantly reduced by silencing or removal of the paraflocculus (PF) of the cerebellum.

The varied path to adulthood: Plasticity in developmental timing in hylobatids.

Maturation includes physical, reproductive, and social aspects that develop asynchronously. Intra- and inter-individual variation in the relative timing of each aspect reflects context-dependent plasticity. Plasticity in developmental timing may be important for the family-living small apes (family Hylobatidae), where reproductive opportunities are monopolized by territorial breeding pairs.

Thermal consequences of increased pelt loft infer an additional utilitarian function for grooming.

A strong case has been made that the primary function of grooming is hygienic. Nevertheless, its persistence in the absence of hygienic demand, and its obvious tactical importance to members of primate groups, underpins the view that grooming has become uncoupled from its utilitarian objectives and is now principally of social benefit. We identify improved thermoregulatory function as a previously unexplored benefit of grooming and so broaden our understanding of the utilitarian function of this behavior.

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

Key Points: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.

Folate metabolic pathway single nucleotide polymorphisms: a predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis.

Aim: We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX).

Patients & Methods: Twelve polymorphisms within nine folate pathway genes were analyzed for association with MTX response in 322 Indian rheumatoid arthritis (RA) patients and MTX pharmacokinetics in 94 RA patients.

Results: Polymorphisms in GGH, SHMT1 and TS were associated with MTX-related adverse events while SNPs in MTHFR and RFC1/SLC19A1 were associated with MTX efficacy.

Obesity and psychological wellbeing in patients undergoing fertility treatment.

Obesity negatively affects reproductive functioning and psychological wellbeing. Distress experienced by infertile women with elevated body mass index (BMI) was investigated. Infertile women (n = 403) were stratified according to World Health Organization (2000) BMI categories (normal, overweight and obese) and infertility category (polycystic ovary syndrome [PCOS] or non-PCOS).

Stimulating effect of graphene oxide on myogenesis of C2C12 myoblasts on RGD peptide-decorated PLGA nanofiber matrices.

Background: In the field of biomedical engineering, many studies have focused on the possible applications of graphene and related nanomaterials due to their potential for use as scaffolds, coating materials and delivery carriers. On the other hand, electrospun nanofiber matrices composed of diverse biocompatible polymers have attracted tremendous attention for tissue engineering and regenerative medicine. However, their combination is intriguing and still challenging.

Longitudinal Trends in Western Australian HIV-1 Sequence Diversity and Viral Transmission Networks and Their Influence on Clinical Parameters: 2000-2014.

We examined baseline HIV-1 protease and reverse transcriptase sequences and HIV clinical parameters from 1,021 consecutive patients (814 male, 207 female) through the Royal Perth Hospital HIV service to investigate HIV-1 subtype diversity and local phylogenetic networks from 2000 to 2014. HIV-1 subtype B virus sequences were demonstrated in 619 (61%) of cases, with increasing non-B HIV-1 subtypes from 23.2% (2000-2003) to 48% (2008-2011) and 43% (2012-2014) (p < 0.

Multifrequency Oscillatory Ventilation in the Premature Lung: Effects on Gas Exchange, Mechanics, and Ventilation Distribution.

Background: Despite the theoretical benefits of high-frequency oscillatory ventilation (HFOV) in preterm infants, systematic reviews of randomized clinical trials do not confirm improved outcomes. The authors hypothesized that oscillating a premature lung with multiple frequencies simultaneously would improve gas exchange compared with traditional single-frequency oscillatory ventilation (SFOV). The goal of this study was to develop a novel method for HFOV, termed "multifrequency oscillatory ventilation" (MFOV), which relies on a broadband flow waveform more suitable for the heterogeneous mechanics of the immature lung.

Musculoskeletal pain is associated with restless legs syndrome in young adults.

Background: In recent years, there is considerable evidence of a relationship between the sensorimotor disorder restless legs syndrome (RLS) and pain disorders, including migraine and fibromyalgia. An association between multi-site pain and RLS has been reported in adult women. In the current study, we explored the association between musculoskeletal (MSK) pain and RLS in a large cohort of young adults.

The Acquisition of Target Dependence by Developing Rat Retinal Ganglion Cells.

Similar to neurons in the peripheral nervous system, immature CNS-derived RGCs become dependent on target-derived neurotrophic support as their axons reach termination sites in the brain. To study the factors that influence this developmental transition we took advantage of the fact that rat RGCs are born, and target innervation occurs, over a protracted period of time. Early-born RGCs have axons in the SC by birth (P0), whereas axons from late-born RGCs do not innervate the SC until P4-P5.

Helicobacter pylori adaptation in vivo in response to a high-salt diet.

Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification of H. pylori is influenced by the composition of the diet.

Impact of digital prosthodontic planning on dental esthetics: Biometric analysis of esthetic parameters.

Statement Of Problem: Improving dental esthetics is a main objective of prosthodontic treatment. Recently, digital diagnostic waxing has been proposed as an alternative to conventional diagnostic waxing; however, the impact on esthetics has not been evaluated.

Purpose: The purpose of this study was to evaluate the impact of diagnostic waxing on biometric esthetic variables and to compare the esthetic outcome achieved by digital waxing with conventional waxing.

Prenatal testosterone exposure is related to sexually dimorphic facial morphology in adulthood.

Prenatal testosterone may have a powerful masculinizing effect on postnatal physical characteristics. However, no study has directly tested this hypothesis. Here, we report a 20-year follow-up study that measured testosterone concentrations from the umbilical cord blood of 97 male and 86 female newborns, and procured three-dimensional facial images on these participants in adulthood (range: 21-24 years).

Disordered eating attitudes and exercise in women undergoing fertility treatment.

Background: Previous research has found a higher lifetime prevalence of eating disorders in women undergoing fertility treatment.

Aims: This study aimed to gauge the prevalence of eating disorders in women attending a fertility clinic and to compare current disordered eating attitudes and exercise amongst different infertility categories.

Materials And Methods: Three hundred and eighty-five women were grouped according to infertility diagnosis: male factor, unexplained infertility, ovulatory disorders, polycystic ovarian syndrome (PCOS) and heterogeneous causations.

Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips.

Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al.

National dental waitlists: what would it take to reset to zero?

Objective Over the years, long public dental waitlists across Australia have received much attention from the media. The issue for eligible patients, namely a further deterioration of dental health because of not being able to address dental concerns relatively quickly, has been the subject of several state and Federal initiatives. The present study provides a cost model for eliminating public dental waitlists across Australia and compares these results with the cost of contracting out public dental care to private clinics.

Modulation of medial geniculate nucleus neuronal activity by electrical stimulation of the nucleus accumbens.

Dysfunctional sensory gating has been proposed to result in the generation of phantom perceptions. In agreement, it has been recently suggested that tinnitus, a phantom perception of sound commonly associated with hearing loss, is the result of a breakdown of circuitry involving the limbic system and the medial geniculate nucleus (MGN) of the thalamus. In humans with tinnitus, structural changes and abnormal activity have been found to occur in the auditory pathway as well as parts of the limbic system such as the nucleus accumbens (NAc).

Dental age estimation standards for a Western Australian population.

Age estimation in the juvenile skeleton primarily relies on the assessment of the degree of dental and skeletal development relative to full maturity. The timing of the mineralization and eruption of the teeth is a sequential process that, compared to skeletal growth and development, is less affected by extrinsic influences such as nutrition and/or chronic illness. Accordingly, radiographic visualization and analysis of different tooth formation stages are the foundation for a number of widely applied age estimation standards.