Non-Stationary Outcome of Alternating Hemiplegia of Childhood into Adulthood

Background Although described as non-progressive, alternating hemiplegia of childhood (AHC) can display a sudden deterioration, anecdotally reported mainly in childhood. Outcome in adulthood is uncertain. Objectives Aim of this study is to describe the long-term follow-up of neurological function in adults with AHC. Methods Seven adults with AHC were included in this retrospective single-center study. Clinical history and previous investigation data were gathered from the review of medical records. Video-documented neurological examination was performed at the last follow-up visit in four out of the seven reported indivisuals. Results Over a median follow-up of 16 years, neurological outcome and trajectories were heterogeneous. All individuals showed new neurological signs or symptoms. Three experienced a serious irreversible neurological deterioration after prolonged quadriplegic episodes and/or status epilepticus in their second or third decade. One patient died at age 29. Conclusions This video-series suggests that AHC in adulthood is not stationary; larger cohorts are needed to identify genotype–phenotype correlations and clinically useful outcome predictors

Non-BBN Constraints On The Key Cosmological Parameters

Since the baryon-to-photon ratio "eta" is in some doubt at present, we ignore the constraints on eta from big bang nucleosynthesis (BBN) and fit the three key cosmological parameters (h, Omega_M, eta) to four other observational constraints: Hubble parameter, age of the universe, cluster gas (baryon) fraction, and effective shape parameter "Gamma". We consider open and flat CDM models and flat "Lambda"-CDM models, testing goodness of fit and drawing confidence regions by the Delta-chi^2 method. CDM models with Omega_M = 1 (SCDM models) are accepted only because we allow a large error on h, permitting h < 0.5. Open CDM models are accepted only for Omega_M \gsim 0.4. Lambda-CDM models give similar results. In all of these models, large eta (\gsim 6) is favored strongly over small eta, supporting reports of low deuterium abundances on some QSO lines of sight, and suggesting that observational determinations of primordial 4He may be contaminated by systematic errors. Only if we drop the crucial Gamma constraint are much lower values of Omega_M and eta permitted.Comment: 12 pages, Kluwer Latex, 2 Postscript figures, to appear in the proceedings of the ISSI Workshop, "The Primordial Nuclei and Their Galactic Evolution" (Bern, May 6-10, 1997), ed. N. Prantzos, M. Tosi, and R. von Steiger (Kluwer, Dordrecht

Imaging Autophagy in hiPSC-Derived Midbrain Dopaminergic Neuronal Cultures for Parkinson’s Disease Research

To appreciate the positive or negative impact of autophagy during the initiation and progression of human diseases, the isolation or de novo generation of appropriate cell types is required to support focused in vitro assays. In human neurodegenerative diseases such as Parkinson’s disease (PD), specific subsets of acutely sensitive neurons become susceptible to stress-associated operational decline and eventual cell death, emphasizing the need for functional studies in those vulnerable groups of neurons. In PD, a class of dopaminergic neurons in the ventral midbrain (mDANs) is affected. To study these, human-induced pluripotent stem cells (hiPSCs) have emerged as a valuable tool, as they enable the establishment and study of mDAN biology in vitro. In this chapter, we describe a stepwise protocol for the generation of mDANs from hiPSCs using a monolayer culture system. We then outline how imaging-based autophagy assessment methodologies can be applied to these neurons, thereby providing a detailed account of the application of imaging-based autophagy assays to human iPSC-derived mDAN

Choice of activity-intensity classification thresholds impacts upon accelerometer-assessed physical activity-health relationships in children

It is unknown whether using different published thresholds (PTs) for classifying physical activity (PA) impacts upon activity-health relationships. This study explored whether relationships between PA (sedentary [SED], light PA [LPA], moderate PA [MPA], moderate-to-vigorous PA, vigorous PA [VPA]) and health markers differed in children when classified using three different PTs

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients

<p>Abstract</p> <p>Background</p> <p>Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.</p> <p>Methods/Design</p> <p>This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.</p> <p>Discussion</p> <p>This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.</p

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Qualidade de vida nas pessoas com esquizofrenia: a influência das características sociodemográficas e clínicas e da satisfação com o suporte social

Objective: To evaluate the relationship of sociodemographic and clinical characteristics and satisfaction with social support with the quality of life of schizophrenic patients. Methodology: This study included a sample of 268 participants. An interview was conducted to obtain sociodemographic and clinical data, supplemented with two assessment tools used to evaluate quality of life (World Health Organization Quality of Life instrument-Abbreviated version – WHOQOL-Bref) and satisfaction with social support (Social Support Satisfaction Scale – SSSS). Descriptive and inferential analyses were performed. Results: Most individuals were male (63.4%), with a mean age of 45.4 years, single (85.4%), living with their family (62.3%) and unemployed (90.3%). As for clinical characteristics, most had the disease for less than 20 years (50.7%), and 55.6% had at least one hospitalization within the last 5 years. Being employed and having had no hospitalization within the last 5 years were positively correlated with one or more WHOQOL-Bref domains. The results of the variables intimacy (p<0.001) and satisfaction with friends (p<0.001) were independently related to the total WHOQOL-Bref score. Conclusion: Having a job, having had no hospitalization within the last 5 years and having greater satisfaction with social support are factors that positively influence quality of life among schizophrenics. It is therefore crucial that the psychosocial rehabilitation of patients with schizophrenia take these factors into account, increasing the support network, preventing relapses and promoting occupational activities.Objetivo: Avaliar a relação entre as características sociodemográficas e clínicas e a satisfação com o suporte social com a qualidade de vida dos doentes com esquizofrenia. Métodos: A amostra do estudo é de 268 participantes. Foi realizada uma entrevista para obter os dados sociodemográficos e clínicos e aplicados dois questionários para avaliar a qualidade de vida (World Health Organization Quality of Life instrument-Abbreviated version – WHOQOL-Bref) e a satisfação com o suporte social (Escala de Satisfação com o Suporte Social – ESSS). Foram efetuadas análises descritivas e inferenciais. Resultados: A maioria dos indivíduos era do gênero masculino (63,4%), com uma média de idade de 45,4 anos, solteiros (85,4%), vivendo com a família (62,3%) e desempregados (90,3%). Relativamente às características clínicas, 50,7% tinham a doença há menos de 20 anos, e 55,6% estiveram internados pelo menos uma vez nos últimos 5 anos. Os resultados demonstraram que estar empregado e não ter sido internado nos últimos 5 anos estão positivamente relacionados com um ou mais domínios da WHOQOL-Bref. A satisfação com a intimidade (p<0,001) e a satisfação com os amigos (p<0,001) foram independentemente associados ao escore total da WHOQOL-Bref. Conclusão: Ter emprego, não ter hospitalizações nos últimos 5 anos e estar satisfeito com o suporte social são fatores que influenciam positivamente a qualidade de vida dos doentes com esquizofrenia. Por conseguinte, é crucial que esses fatores sejam levados em conta nos programas de reabilitação com o suporte social, aumentando a rede de suporte, evitando recaídas e promovendo atividades ocupacionais.publishe

Rapid in situ imaging and whole genome sequencing of biofilm in neonatal feeding tubes: a clinical proof of concept

The bacterial flora of nasogastric feeding tubes and faecal samples were analysed for a low-birth weight (725g) neonate EGA 25 weeks in intensive care. Samples were collected at age 6 and 8 weeks of life. Optical coherence tomography (OCT) was used to visualise bacterial biofilms inside the nasogastric feeding tubes. The biofilm was heterogeneously distributed along the tube lumen wall, and had a depth of up to 500µm. The bacterial biofilm and faecal samples included Enterococcus faecalis and Enterobacter hormaechei. Representative strains, recovered from both feeding tubes and faecal samples, were whole genome sequenced using Illumina, Mi-Seq, which revealed indistinguishable strains, each with less than 28 SNP differences, of E. faecalis and E. hormaechei. The E. faecalis strains were from two sequence types (ST191 and ST211) and encoded for a number of traits related to biofilm formation (BopD), adherence (Epb pili), virulence (cps loci, gelatinase, SprE) and antibiotic resistances (IsaA, tetM). The E. hormaechei were all ST106, and encoded for blaACT-15 β–lactamase and fosfomycin resistance (fosA). This proof of concept study demonstrates that bacterial flora within the neonatal feeding tubes may influence the bacterial colonisation of the intestinal tract and can be visualised nondestructively using OCT