Evaluating movement disorders in pediatric patients receiving risperidone: a comparison of spontaneous reports and research criteria for TD

<p>Abstract</p> <p>Background</p> <p>Movement disorders (MD) in children are relatively common and may be associated with medication use. Objective methods (ie rating scales) and specific research criteria may be helpful in identifying MD-related adverse events that would otherwise not be apparent from spontaneous reports. We assessed whether more stringent and rigorous criteria would provide MD rates similar to those derived subjectively from spontaneous reports.</p> <p>Methods</p> <p>MDs were assessed in children with disruptive behavior disorders (DBDs) and subaverage intelligence receiving risperidone. Data were from three 1-year, open-label studies in subjects 4–14 years old. Dyskinesia severity was rated by the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale. Tardive dyskinesia (TD) was defined: mild dyskinesia (scores 2, 3) in two anatomical areas; or moderate dyskinesia (score ≥ 4) in one area for ≥ 4 weeks in subjects without dyskinesia at baseline (scores 0, 1).</p> <p>Results</p> <p>The mean (± SD) age of subjects was 9.4 ± 2.4 years, the mean (± SD) risperidone dose was 1.6 ± 0.7 mg/day, and the mean (± SD) exposure was 317.8 ± 104.5 days. ESRS data were available for 668 subjects. Mean ESRS scores were low throughout the study. At baseline, 655 subjects had no dyskinetic symptoms. One subject met predefined TD criteria after a risperidone dose reduction. Symptoms persisted for 4 weeks, resolving with continued treatment and no dosage change. Two different subjects had TD by spontaneous adverse-event reports, with dyskinetic symptoms at 1–2 visits, and symptoms that resolved after treatment discontinuation. Thirteen subjects had dyskinesia at baseline; their mean ESRS dyskinesia scores decreased at endpoint.</p> <p>Conclusion</p> <p>Using objective rating scales and research criteria, low-dose risperidone was associated with low risk of TD and other MDs in children with DBDs in three large 1-year studies. Careful, objective evaluation of emergent MDs during all stages of treatment is essential for identifying treatment-emergent TD.</p

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Reprogramming of Escherichia coli K-12 Metabolism during the Initial Phase of Transition from an Anaerobic to a Micro-Aerobic Environment

Background: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Methods and Findings: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Conclusion: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions

The weight-loss experience : qualitative exploration

BACKGROUND: Long-term weight management consists of weight-loss, weight-loss maintenance, and weight-gain stages. Qualitative insights into weight management are now appearing in the literature however research appears to be biased towards explorations of weight-loss maintenance. The qualitative understanding of weight loss, which begets weight-loss maintenance and might establish the experiences and behaviours necessary for successful long-term weight management, is comparatively under-investigated. The aim of this study was to investigate the weight-loss experiences of a sample of participants not aligned to clinical intervention research, in order to understand the weight-loss experiences of a naturalistic sample. METHODS: Participants (n=8) with weight-loss (n=4) and weight-maintenance experiences (n=4) were interviewed using a semi-structured interview to understand the weight-loss experience. Interview data was analysed thematically using Framework Analysis and was underpinned by realist meta-theory. RESULTS: Weight loss was experienced as an enduring challenge, where factors that assisted weight loss were developed and experienced dichotomously to factors that hindered it. Participants described barriers to (dichotomous thinking, environments, social pressures and weight centeredness) and facilitators of (mindfulness, knowledge, exercise, readiness to change, structure, self-monitoring and social support) their weight-loss goals in rich detail, highlighting that weight loss was a complex experience. CONCLUSIONS: Weight loss was a difficult task, with physical, social, behavioural and environmental that appeared to assist and inhibit weight-loss efforts concurrently. Health professionals might need to better understand the day-to-day challenges of dieters in order to provide more effective, tailored treatments. Future research should look to investigate the psycho-social consequences of weight-loss dieting, in particular self-imposed social exclusion and spousal sabotage and flexible approaches to treatment

Smoking Dose Modifies the Association between C242T Polymorphism and Prevalence of Metabolic Syndrome in a Chinese Population

Background: The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. Oxidase is a major source of the superoxide anion that contributes to individual components of metabolic syndrome. We examined the relationship of the C242T polymorphism with the prevalence of metabolic syndrome in a Chinese population, taking account of consumed cigarette amounts. Methodology/Principal Findings: In 870 participants, we collected biomarkers related to metabolic syndrome and detailed history of smoking and genotyped the C242T polymorphisms. After adjustment for covariates, the CT/TT genotypes were associated with a lower risk of metabolic syndrome (P = 0.0008). The odds of having metabolic syndrome in the CT/TT participants were 0.439 (95%CI: 0.265, 0.726), while for CC participants the odds were 1.110 (95%CI: 0.904, 1.362). There was significant (P = 0.014) interaction between the C242T polymorphism and smoking status in relation to the prevalence of metabolic syndrome. For smokers who smoke no less than 25 pack-years, those with CT/TT genotypes had lower risk of metabolic syndrome as compared with CC polymorphism carriers (P = 0.015). In the multiple regression analysis, the CT/TT genotypes were significantly associated with lower serum concentration of triglycerides both in all subjects and smokers; furthermore, the CT/TT genotypes were also related to smaller waist circumference in smokers. Conclusions: Our study suggests that the C242T gene polymorphism is indeed related to the prevalence of metaboli

Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials

Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

Adolescent Loneliness and Social Skills:Agreement and Discrepancies Between Self-, Meta-, and Peer-Evaluations

Contains fulltext : 160961.pdf (publisher's version ) (Open Access)Lonely adolescents report that they have poor social skills, but it is unknown whether this is due to an accurate perception of a social skills deficit, or a biased negative perception. This is an important distinction, as actual social skills deficits require different treatments than biased negative perceptions. In this study, we compared self-reported social skills evaluations with peer-reported social skills and meta-evaluations of social skills (i.e., adolescents' perceptions of how they believe their classmates evaluate them). Based on the social skills view, we expected negative relations between loneliness and these three forms of social skills evaluations. Based on the bias view, we expected lonely adolescents to have more negative self- and meta-evaluations compared to peer-evaluations of social skills. Participants were 1342 adolescents (48.64 % male, M age = 13.95, SD = .54). All classmates rated each other in a round-robin design to obtain peer-evaluations. Self- and meta-evaluations were obtained using self-reports. Data were analyzed using polynomial regression analyses and response surface modeling. The results indicated that, when self-, peer- and meta-evaluations were similar, a greater sense of loneliness was related to poorer social skills. Loneliness was also related to larger discrepancies between self- and peer-evaluations of loneliness, but not related to the direction of these discrepancies. Thus, for some lonely adolescents, loneliness may be related to an actual social skills deficit, whereas for others a biased negative perception of one's own social skills or a mismatch with the environment may be related to their loneliness. This implies that different mechanisms may underlie loneliness, which has implications for interventions.11 p

Convergent trends and spatiotemporal patterns of Aedes-borne arboviruses in Mexico and Central America

Background Aedes-borne arboviruses cause both seasonal epidemics and emerging outbreaks with a significant impact on global health. These viruses share mosquito vector species, often infecting the same host population within overlapping geographic regions. Thus, comparative analyses of the virus evolutionary and epidemiological dynamics across spatial and temporal scales could reveal convergent trends. Methodology/Principal findings Focusing on Mexico as a case study, we generated novel chikungunya and dengue (CHIKV, DENV-1 and DENV-2) virus genomes from an epidemiological surveillance-derived historical sample collection, and analysed them together with longitudinally-collected genome and epidemiological data from the Americas. Aedes-borne arboviruses endemically circulating within the country were found to be introduced multiple times from lineages predominantly sampled from the Caribbean and Central America. For CHIKV, at least thirteen introductions were inferred over a year, with six of these leading to persistent transmission chains. For both DENV-1 and DENV-2, at least seven introductions were inferred over a decade. Conclusions/Significance Our results suggest that CHIKV, DENV-1 and DENV-2 in Mexico share evolutionary and epidemiological trajectories. The southwest region of the country was determined to be the most likely location for viral introductions from abroad, with a subsequent spread into the Pacific coast towards the north of Mexico. Virus diffusion patterns observed across the country are likely driven by multiple factors, including mobility linked to human migration from Central towards North America. Considering Mexico’s geographic positioning displaying a high human mobility across borders, our results prompt the need to better understand the role of anthropogenic factors in the transmission dynamics of Aedes-borne arboviruses, particularly linked to land-based human migration