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

Identification of the barrier to gene flow between phylogeographic lineages of the common hamster Cricetus cricetus

In anthropogenically disturbed habitats, natural barriers still exist and have to be recognized, as they are important for conservation measures. Areas of phylogeographic breaks within a species are often stabilized in inhospitable regions which act as natural barriers. An area of contact between phylogeographic lineages of the common hamster (Cricetus cricetus) was found in the Małopolska Upland in Poland. A total of 142 common hamsters were captured between 2005 and 2009. All hamsters were genotyped at 17 microsatellite loci and partial sequences of the mitochondrial (mtDNA) control region were obtained. No mixed populations with mtDNA haplotypes of both lineages were found. The distance between marginal populations was about 20 km; no hamsters were found in the area between. A principal components analysis (PCA) was performed on microsatellite data and the greatest change in PC1 scores was found between marginal samples. To define the habitat components responsible for the phylogeographic break, we compared the habitat composition of sites occupied by hamsters with those from which hamsters were absent. We found that hamsters avoided forested areas and sandy soils. The area of the potential barrier was characterized by a high proportion of woodland and unfavorable soils in comparison with neighboring areas inhabited by hamsters. They cannot settle in this area due to their high winter mortality in shallow burrows and high predation in the fields adjacent to forests

The impact on sleep of a multidisciplinary cognitive behavioural pain management programme: a pilot study

Background: Reduced sleep quality is a common complaint among patients with chronic pain, with 50-80% of patients reporting sleep disturbance. Improvements in pain and quality of life measures have been achieved using a multidisciplinary cognitive behavioural therapy pain management programme (CBT-PMP) that aims to recondition attitudes to pain, and improve patients' self-management of their condition. Despite its high prevalence in patients with chronic pain, there is very limited objective evidence for the effect of this intervention on sleep quality. The primary research objective is to investigate the short-term effect of a multidisciplinary CBTPMP on subjective (measured by Pittsburg Sleep Quality Index) and objective sleep quality (measured by Actigraphy) in patients with chronic pain by comparison with a control group. The secondary objectives will investigate changes in function and mood, and then explore the relationship between objective and subjective sleep quality and physical and psychological outcome measures. Methods/Design: Patients who fulfil the inclusion criteria for attendance on the multidisciplinary CBT-PMP in the Adelaide and Meath Hospital, Tallaght, Dublin and are currently listed on the PMP waiting list will be invited to participate in this pilot study. Potential patients will be screened for sleep disturbance [determined by the Pittsburgh Sleep Quality Index (PSQI)]. Those patients with a sleep disturbance (PSQI >5) will be assigned to either the intervention group (immediate treatment), or control group (deferred treatment, i.e. the PMP they are listed for is more than six months away) based on where they appear on the waiting list. Baseline measures of sleep, function, and mood will be obtained using a combination of self-report questionnaires (the Hospital Anxiety and Depression Scale, the Short Form 36 health survey, the Pittsburgh Sleep Quality Index, the Tampa Scale for Kinesiophobia), and functional outcome measures. Sleep will be measured for seven days using actigraphy (Actiwatch 7). These measures will be repeated after the four week multidisciplinary cognitive behavioural therapy pain management programme, and at a two month follow-up. The waiting list control group will be assessed at baseline, and two months later. Analysis for the primary outcome will include between group differences of subjective and objective sleep parameters from baseline to follow-up using Independent T-tests or Mann-Whitney U tests. The secondary outcomes establishing relationships between the sleep variables and physical and psychological outcome measures will be established using multiple linear regression models. Discussion: This pilot study will evaluate the impact of a multidisciplinary CBT-PMP on both subjective and objective measures of sleep in patients with chronic pain and provide guidance for a larger clinical trial. Trial Registration: Current controlled trial ISRCTN: ISRCTN7491359

Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia

Eggs in the Freezer: Energetic Consequences of Nest Site and Nest Design in Arctic Breeding Shorebirds

Birds construct nests for several reasons. For species that breed in the Arctic, the insulative properties of nests are very important. Incubation is costly there and due to an increasing surface to volume ratio, more so in smaller species. Small species are therefore more likely to place their nests in thermally favourable microhabitats and/or to invest more in nest insulation than large species. To test this hypothesis, we examined characteristics of nests of six Arctic breeding shorebird species. All species chose thermally favourable nesting sites in a higher proportion than expected on the basis of habitat availability. Site choice did not differ between species. Depth to frozen ground, measured near the nests, decreased in the course of the season at similar non-species-specific speeds, but this depth increased with species size. Nest cup depth and nest scrape depth (nest cup without the lining) were unrelated to body mass (we applied an exponent of 0.73, to account for metabolic activity of the differently sized species). Cup depth divided by diameter2 was used as a measure of nest cup shape. Small species had narrow and deep nests, while large species had wide shallow nests. The thickness of nest lining varied between 0.1 cm and 7.6 cm, and decreased significantly with body mass. We reconstruct the combined effect of different nest properties on the egg cooling coefficient using previously published quantitative relationships. The predicted effect of nest cup depth and lining depth on heat loss to the frozen ground did not correlate with body mass, but the sheltering effect of nest cup diameter against wind and the effects of lining material on the cooling coefficient increased with body mass. Our results suggest that small arctic shorebirds invest more in the insulation of their nests than large species

There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

Höhn S, Hallmann A. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator. BMC Biology. 2011;9(1): 89.Background: Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results: In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions: Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator

Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits

Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems

Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options