High dietary fat consumption impairs axonal mitochondrial function in vivo

Peripheral neuropathy (PN) is the most common complication of prediabetes and diabetes. PN causes severe morbidity for Type 2 diabetes (T2D) and prediabetes patients, including limb pain followed by numbness resulting from peripheral nerve damage. PN in T2D and prediabetes is associated with dyslipidemia and elevated circulating lipids; however, the molecular mechanisms underlying PN development in prediabetes and T2D are unknown. Peripheral nerve sensory neurons rely on axonal mitochondria to provide energy for nerve impulse conduction under homeostatic conditions. Models of dyslipidemia in vitro demonstrate mitochondrial dysfunction in sensory neurons exposed to elevated levels of exogenous fatty acids. Herein, we evaluated the effect of dyslipidemia on mitochondrial function and dynamics in sensory axons of the saphenous nerve of a male high-fat diet (HFD)-fed murine model of prediabetes to identify mitochondrial alterations that correlate with PN pathogenesis in vivo. We found that the HFD decreased mitochondrial membrane potential (MMP) in axonal mitochondria and reduced the ability of sensory neurons to conduct at physiological frequencies. Unlike mitochondria in control axons, which dissipated their MMP in response to increased impulse frequency (from 1 to 50 Hz), HFD mitochondria dissipated less MMP in response to axonal energy demand, suggesting a lack of reserve capacity. The HFD also decreased sensory axonal Ca^{2+} levels and increased mitochondrial lengthening and expression of PGC1α, a master regulator of mitochondrial biogenesis. Together, these results suggest that mitochondrial dysfunction underlies an imbalance of axonal energy and Ca^{2+} levels and impairs impulse conduction within the saphenous nerve in prediabetic PN

The EMBLA survey - metal-poor stars in the Galactic bulge

Cosmological models predict the oldest stars in the Galaxy should be found closest to the centre of the potential well, in the bulge. The Extremely Metal-poor BuLge stars with AAOmega survey (EMBLA) successfully searched for these old, metal-poor stars by making use of the distinctive SkyMapper photometric filters to discover candidate metal-poor stars in the bulge. Their metal-poor nature was then confirmed using the AAOmega spectrograph on the Anglo-Australian Telescope. Here we present an abundance analysis of 10 bulge stars with −2.8 < [Fe/H] < −1.7 from MIKE/Magellan observations, in total determining the abundances of 22 elements. Combining these results with our previous high-resolution data taken as part of the Gaia-ESO Survey, we have started to put together a picture of the chemical and kinematic nature of the most metal-poor stars in the bulge. The currently available kinematic data are consistent with the stars belonging to the bulge, although more accurate measurements are needed to constrain the stars’ orbits. The chemistry of these bulge stars deviates from that found in halo stars of the same metallicity. Two notable differences are the absence of carbon-enhanced metal-poor bulge stars, and the α element abundances exhibit a large intrinsic scatter and include stars which are underabundant in these typically enhanced elements.LMH and MA have been supported by the Australian Research Council (grant FL110100012). ARC acknowledges support from the European Union FP7 programme through ERC grant number 320360. DY is supported through an Australian Research Council Future Fellowship (FT140100554). Research on metal-poor stars with SkyMapper is supported through Australian Research Council Discovery Projects grants DP120101237 and DP150103294 (PI: Da Costa). This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. This paper includes data gathered with the 6.5 metre Magellan Telescopes located at Las Campanas Observatory, Chile.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw100

Replication of a whole school ethos-changing intervention: different context, similar effects, additional insights

Background Whole school, ethos-changing interventions reduce risk behaviours in middle adolescence, more than curriculum-based approaches. Effects on older ages are not known. We set out to replicate one of these interventions, Australia’s Gatehouse Project, in a rural Canadian high school. Methods A guided, whole school change process sought to make students feel more safe, connected, and valued by: changes in teaching practices, orientation processes, professional development of staff, recognition and reward mechanisms, elevating student voice, and strategies to involve greater proactivity and participation. We conducted risk behaviour surveys in grades 10 to 12 before the intervention and 2 years afterwards, and social network analyses with the staff. Changes in health and health risk behaviours were assessed using chi-square. Interactions between the intervention and gender and between the intervention and school engagement were assessed using interaction terms in logistic regression models. Changes in the density of relationships among staff were tested with methods analogous to paired t-tests. Results Like Gatehouse, there was no statistically significant reduction in depressive symptoms or bullying, though the trend was in that direction. Among girls, there was a statistically significant decrease in low school engagement (45% relative reduction), and decreases in drinking (46% relative reduction), unprotected sex (61% relative reduction) and poor health (relative reduction of 73%). The reduction in drinking matched the national trend. Reductions in unprotected sex and poor health went against the national trend. We found no statistically significant changes for boys. The effects coincided with statistically significant increases in the densities of staff networks, indicating that part of the mechanism may be through relationships at school. Conclusions A non-specific, risk protective intervention in the social environment of the school had a significant impact on a cluster of risk behaviours for girls. Results were remarkably like reports from similar school environment interventions elsewhere, albeit with different behaviours being affected. It may be that this type of intervention activates change processes that interact highly with context, impacting different risks differently, according to the prevalence, salience and distribution of the risk and the interconnectivity of relationships between staff and students. This requires further exploration.14 page(s

Changing insurance company claims handling processes improves some outcomes for people injured in road traffic crashes

<p>Abstract</p> <p>Background</p> <p>Regaining good health and returning to work are important for people injured in road traffic crashes and for society. The handling of claims by insurance companies may play an important role in the rate at which health recovers and return to work is actually attained.</p> <p>Methods</p> <p>A novel approach towards claims handling for people injured in road traffic accidents was compared to the standard approach. The setting was a large insurance company (NRMA Insurance) in the state of New South Wales, Australia. The new approach involved communicating effectively with injured people, early intervention, screening for adverse prognostic factors and focusing on early return to work and usual activities. Demographic and injury data, health outcomes, return to work and usual activities were collected at baseline and 7 months post-injury.</p> <p>Results</p> <p>Significant differences were found 7 months post-injury on 'caseness' of depression (<it>p </it>= 0.04), perceived health limitation on activities (<it>p </it>= 0.03), and self-reported return to usual activities (<it>p </it>= 0.01) with the intervention group scoring better. Baseline general health was a significant predictor for general health at 7 months (OR 11.6, 95% CI 2.7-49.4) and for return to usual activities (OR 4.6, 95% CI 2.3-9.3).</p> <p>Conclusion</p> <p>We found a few positive effects on health from a new claims handling method by a large insurance company. It may be most effective to target people who report low general health and low expectations for their health recovery when they file their claim.</p

Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study)

Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

The emerging role of cell surface receptor and protein binding radiopharmaceuticals in cancer diagnostics and therapy

Targeting specific cell membrane markers for both diagnostic imaging and radionuclide therapy is a rapidly evolving field in cancer research. Some of these applications have now found a role in routine clinical practice and have been shown to have a significant impact on patient management. Several molecular targets are being investigated in ongoing clinical trials and show promise for future implementation. Advancements in molecular biology have facilitated the identification of new cancer-specific targets for radiopharmaceutical development.This work was supported by Cancer Research UK, the CRUK Cambridge Centre, the CRUK & Engineering and Physical Science Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester, the Mark Foundation for Cancer Research, Addenbrooke's Charitable Trust, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, CRUK National Cancer Imaging Translational Accelerator (NCITA)

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed