The aetiology of idiopathic Parkinson's disease

Agents potentially involved in the aetiology of idiopathic Parkinson's disease are discussed. These include factors regulating dopaminergic neurogenesis (Nurr 1, Ptx-3, and Lmx1b) and related proteins, together with genes involved in familial Parkinson's disease (α synuclein, parkin, and ubiquitin carboxy terminal hydroxylase L1), and endogenous and environmental agents.published_or_final_versio

Constrictive pericarditis is an easily overlooked cause of right heart failure: a case report

We describe a patient who suffered progressive right heart failure of unknown aetiology, despite a lengthy series of hospital investigations. Constrictive pericarditis had not been suspected during life, and was ultimately diagnosed as an autopsy finding. The salient clinical features and confirmatory investigations for this unusual disorder are reviewed. The case reminds us to consider the possibility of constrictive pericarditis in patients with unexplained chronic right heart failure, so that prompt investigation and treatment can be instigated

Does Work Affect Personality? A Study in Horses

It has been repeatedly hypothesized that job characteristics are related to changes in personality in humans, but often personality models still omit effects of life experience. Demonstrating reciprocal relationships between personality and work remains a challenge though, as in humans, many other influential factors may interfere. This study investigates this relationship by comparing the emotional reactivity of horses that differed only by their type of work. Horses are remarkable animal models to investigate this question as they share with humans working activities and their potential difficulties, such as “interpersonal” conflicts or “suppressed emotions”. An earlier study showed that different types of work could be associated with different chronic behavioural disorders. Here, we hypothesised that type of work would affect horses' personality. Therefore over one hundred adult horses, differing only by their work characteristics were presented standardised behavioural tests. Subjects lived under the same conditions (same housing, same food), were of the same sex (geldings), and mostly one of two breeds, and had not been genetically selected for their current type of work. This is to our knowledge the first time that a direct relationship between type of work and personality traits has been investigated. Our results show that horses from different types of work differ not as much in their overall emotional levels as in the ways they express emotions (i.e. behavioural profile). Extremes were dressage horses, which presented the highest excitation components, and voltige horses, which were the quietest. The horses' type of work was decided by the stall managers, mostly on their jumping abilities, but unconscious choice based on individual behavioural characteristics cannot be totally excluded. Further research would require manipulating type of work. Our results nevertheless agree with reports on humans and suggest that more attention should be given to work characteristics when evaluating personalities

Interaction between drug and placebo effects: a cross-over balanced placebo design trial

<p>Abstract</p> <p>Background</p> <p>The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.</p> <p>Methods</p> <p>180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.</p> <p>Results</p> <p>The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).</p> <p>Conclusions</p> <p>Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identification number - NCT00426010.</p

Moving toward a system genetics view of disease

Testing hundreds of thousands of DNA markers in human, mouse, and other species for association to complex traits like disease is now a reality. However, information on how variations in DNA impact complex physiologic processes flows through transcriptional and other molecular networks. In other words, DNA variations impact complex diseases through the perturbations they cause to transcriptional and other biological networks, and these molecular phenotypes are intermediate to clinically defined disease. Because it is also now possible to monitor transcript levels in a comprehensive fashion, integrating DNA variation, transcription, and phenotypic data has the potential to enhance identification of the associations between DNA variation and diseases like obesity and diabetes, as well as characterize those parts of the molecular networks that drive these diseases. Toward that end, we review methods for integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data to infer causal relationships among gene expression traits and between expression and clinical traits. We further describe methods to integrate these data in a more comprehensive manner by constructing coexpression gene networks that leverage pairwise gene interaction data to represent more general relationships. To infer gene networks that capture causal information, we describe a Bayesian algorithm that further integrates eQTLs, expression, and clinical phenotype data to reconstruct whole-gene networks capable of representing causal relationships among genes and traits in the network. These emerging network approaches, aimed at processing high-dimensional biological data by integrating data from multiple sources, represent some of the first steps in statistical genetics to identify multiple genetic perturbations that alter the states of molecular networks and that in turn push systems into disease states. Evolving statistical procedures that operate on networks will be critical to extracting information related to complex phenotypes like disease, as research goes beyond a single-gene focus. The early successes achieved with the methods described herein suggest that these more integrative genomics approaches to dissecting disease traits will significantly enhance the identification of key drivers of disease beyond what could be achieved by genetic association studies alone

The home environment and childhood obesity in low-income households: indirect effects via sleep duration and screen time

Background Childhood obesity disproportionally affects children from low-income households. With the aim of informing interventions, this study examined pathways through which the physical and social home environment may promote childhood overweight/obesity in low-income households. Methods Data on health behaviors and the home environment were collected at home visits in low-income, urban households with either only normal weight (n = 48) or predominantly overweight/obese (n = 55) children aged 6–13 years. Research staff conducted comprehensive, in-person audits of the foods, media, and sports equipment in each household. Anthropometric measurements were collected, and children’s physical activity was assessed through accelerometry. Caregivers and children jointly reported on child sleep duration, screen time, and dietary intake of foods previously implicated in childhood obesity risk. Path analysis was used to test direct and indirect associations between the home environment and child weight status via the health behaviors assessed. Results Sleep duration was the only health behavior associated with child weight status (OR = 0.45, 95% CI: 0.27, 0.77), with normal weight children sleeping 33.3 minutes/day longer on average than overweight/obese children. The best-fitting path model explained 26% of variance in child weight status, and included paths linking chaos in the home environment, lower caregiver screen time monitoring, inconsistent implementation of bedtime routines, and the presence of a television in children’s bedrooms to childhood overweight/obesity through effects on screen time and sleep duration. Conclusions This study adds to the existing literature by identifying aspects of the home environment that influence childhood weight status via indirect effects on screen time and sleep duration in children from low-income households. Pediatric weight management interventions for low-income households may be improved by targeting aspects of the physical and social home environment associated with sleep

Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn’s disease: an observational study

Background/Objectives: Enteral feeding will induce remission in as many as 80–90% of compliant patients with active Crohn’s disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. Methods/Subjects: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. Results: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. Conclusions: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD

Tight coupling of leaf area index to canopy nitrogen and phosphorus across heterogeneous tallgrass prairie communities

Nitrogen (N) and phosphorus (P) are limiting nutrients for many plant communities worldwide. Foliar N and P along with leaf area are among the most important controls on photosynthesis and hence productivity. However, foliar N and P are typically assessed as species level traits, whereas productivity is often measured at the community scale. Here, we compared the community-level traits of leaf area index (LAI) to total foliar nitrogen (TFN) and total foliar phosphorus (TFP) across nearly three orders of magnitude LAI in grazed and ungrazed tallgrass prairie in north-eastern Kansas, USA. LAI was strongly correlated with both TFN and TFP across communities, and also within plant functional types (grass, forb, woody, and sedge) and grazing treatments (bison or cattle, and ungrazed). Across almost the entire range of LAI values and contrasting communities, TFN:TFP ratios indicated co-limitation by N and P in almost all communities; this may further indicate a community scale trend of an optimal N and P allocation per unit leaf area for growth. Previously, results from the arctic showed similar tight relationships between LAI:TFN, suggesting N is supplied to canopies to maximize photosynthesis per unit leaf area. This tight coupling between LAI, N, and P in tallgrass prairie suggests a process of optimal allocation of N and P, wherein LAI remains similarly constrained by N and P despite differences in species composition, grazing, and canopy density

Drosophila Eggshell Production: Identification of New Genes and Coordination by Pxt

Drosophila ovarian follicles complete development using a spatially and temporally controlled maturation process in which they resume meiosis and secrete a multi-layered, protective eggshell before undergoing arrest and/or ovulation. Microarray analysis revealed more than 150 genes that are expressed in a stage-specific manner during the last 24 hours of follicle development. These include all 30 previously known eggshell genes, as well as 19 new candidate chorion genes and 100 other genes likely to participate in maturation. Mutations in pxt, encoding a putative Drosophila cyclooxygenase, cause many transcripts to begin expression prematurely, and are associated with eggshell defects. Somatic activity of Pxt is required, as RNAi knockdown of pxt in the follicle cells recapitulates both the temporal expression and eggshell defects. One of the temporally regulated genes, cyp18a1, which encodes a cytochromome P450 protein mediating ecdysone turnover, is downregulated in pxt mutant follicles, and cyp18a1 mutation itself alters eggshell gene expression. These studies further define the molecular program of Drosophila follicle maturation and support the idea that it is coordinated by lipid and steroid hormonal signals