Do patients prefer optimistic or cautious psychiatrists? An experimental study with new and long-term patients

Abstract Background Patients seeking treatment may be assumed to prefer a psychiatrist who suggests a new treatment with confidence and optimism. Yet, this might not apply uniformly to all patients. In this study, we tested the hypothesis that new patients prefer psychiatrists who present treatments optimistically, whilst patients with longer-term experience of mental health care may rather prefer more cautious psychiatrists. Methods In an experimental study, we produced video-clips of four psychiatrists, each suggesting a pharmacological and a psychological treatment once with optimism and once with caution. 100 \u2018new\u2019 patients with less than 3\ua0months experience of mental health care and 100 \u2018long-term\u2019 patients with more than one year of experience were shown a random selection of one video-clip from each psychiatrist, always including an optimistic and a cautious suggestion of each treatment. Patients rated their preferences for psychiatrists on Likert type scales. Differences in subgroups with different age (18\u201340 vs. 41\u201365 years), gender, school leaving age (\u226416 vs. >16\ua0years), and diagnosis (ICD 10\ua0F2 vs. others) were explored. Results New patients preferred more optimistic treatment suggestions, whilst there was no preference among long-term patients. The interaction effect between preference for treatment presentations and experience of patients was significant (interaction p -value\u2009=\u20090.003). Findings in subgroups were similar. Conclusion In line with the hypothesis, psychiatrists should suggest treatments with optimism to patients with little experience of mental health care. However, this rule does not apply to longer-term patients, who may have experienced treatment failures in the past

EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans

Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Development of a method for environmentally friendly chemical peptide synthesis in water using water-dispersible amino acid nanoparticles

Due to the vast importance of peptides in biological processes, there is an escalating need for synthetic peptides to be used in a wide variety of applications. However, the consumption of organic solvent is extremely large in chemical peptide syntheses because of the multiple condensation steps in organic solvents. That is, the current synthesis method is not environmentally friendly. From the viewpoint of green sustainable chemistry, we focused on developing an organic solvent-free synthetic method using water, an environmentally friendly solvent. Here we described in-water synthesis technology using water-dispersible protected amino acids

Phone and e-mail counselling are effective for weight management in an overweight working population: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The work setting provides an opportunity to introduce overweight (i.e., Body Mass Index ≥ 25 kg/m²) adults to a weight management programme, but new approaches are needed in this setting. The main purpose of this study was to investigate the effectiveness of lifestyle counselling by phone or e-mail on body weight, in an overweight working population. Secondary purposes were to establish effects on waist circumference and lifestyle behaviours, and to assess which communication method is the most effective.</p> <p>Methods</p> <p>A randomized controlled trial with three treatments: intervention materials with phone counselling (phone group); a web-based intervention with e-mail counselling (internet group); and usual care, i.e. lifestyle brochures (control group). The interventions used lifestyle modification and lasted a maximum of six months. Subjects were 1386 employees, recruited from seven companies (67% male; mean age 43 (SD 8.6) y; mean BMI 29.6 (SD 3.5) kg/m²). Body weight was measured by research personnel and by questionnaire. Secondary outcomes fat, fruit and vegetable intake, physical activity and waist circumference were assessed by questionnaire. Measurements were done at baseline and after six months. Missing body weight was multiply imputed.</p> <p>Results</p> <p>Body weight reduced 1.5 kg (95% CI -2.2;-0.8, p < 0.001) in the phone group and 0.6 kg (95% CI -1.3; -0.01, p = 0.045) in the internet group, compared with controls. In completers analyses, weight and waist circumference in the phone group were reduced with 1.6 kg (95% CI -2.2;-1.0, p < 0.001) and 1.9 cm (95% CI -2.7;-1.0, p < 0.001) respectively, fat intake decreased with 1 fatpoint (1 to 4 grams)/day (95% CI -1.7;-0.2, p = 0.01) and physical activity increased with 866 METminutes/week (95% CI 203;1530, p = 0.01), compared with controls. The internet intervention resulted in a weight loss of 1.1 kg (95% CI -1.7;-0.5, p < 0.001) and a reduction in waist circumference of 1.2 cm (95% CI -2.1;-0.4, p = 0.01), in comparison with usual care. The phone group appeared to have more and larger changes than the internet group, but comparisons revealed no significant differences.</p> <p>Conclusion</p> <p>Lifestyle counselling by phone and e-mail is effective for weight management in overweight employees and shows potential for use in the work setting.</p> <p>Trial registration</p> <p>ISCRTN04265725.</p

The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training

The extent of skeletal muscle hypertrophy in response to resistance training is highly variable in humans. The main objective of this study was to explain the nature of this variability. More specifically, we focused on the myogenic stem cell population, the satellite cell (SC) as a potential mediator of hypertrophy. Twenty-three males (aged 18–35 yrs) participated in 16 wk of progressive, whole body resistance training, resulting in changes of 7.9±1.6% (range of −1.9–24.7%) and 21.0±4.0% (range of −7.0 to 51.7%) in quadriceps volume and myofibre cross-sectional area (CSA), respectively. The SC response to a single bout of resistance exercise (80% 1RM), analyzed via immunofluorescent staining resulted in an expansion of type II fibre associated SC 72 h following exercise (pre: 11.3±0.9; 72 h: 14.8±1.4 SC/type II fibre; p<0.05). Training resulted in an expansion of the SC pool associated with type I (pre: 10.7±1.1; post: 12.1±1.2 SC/type I fibre; p<0.05) and type II fibres (pre: 11.3±0.9; post: 13.0±1.2 SC/type II fibre; p<0.05). Analysis of individual SC responses revealed a correlation between the relative change in type I associated SC 24 to 72 hours following an acute bout of resistance exercise and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.566, p = 0.012) and the relative change in type II associated SC following 16 weeks of resistance training and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.493, p = 0.027). Our results suggest that the SC response to resistance exercise is related to the extent of muscular hypertrophy induced by training

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS).\ud \ud METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response.\ud \ud RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay.\ud \ud CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS

The effectiveness of physical activity monitoring and distance counselling in an occupational health setting - a research protocol for a randomised controlled trial (CoAct)

<p>Abstract</p> <p>Background</p> <p>The CoAct (Cocreating Activity) study is investigating a novel lifestyle intervention, aimed at the working population, with daily activity monitoring and distance counselling via telephone and secure web messages. The main purpose of this study is to evaluate the effectiveness of lifestyle counselling on the level of physical activity in an occupational health setting. The purposes include also analysing the potential effects of changes in physical activity on productivity at work and sickness absence, and healthcare costs. This article describes the design of the study and the participant flow until and including randomization.</p> <p>Methods/Design</p> <p>CoAct is a randomised controlled trial with two arms: a control group and intervention group with daily activity monitoring and distance counselling. The intervention focuses on lifestyle modification and takes 12 months. The study population consists of volunteers from 1100 eligible employees of a Finnish insurance company. The primary outcomes of this study are change in physical activity measured in MET minutes per week, work productivity and sickness absence, and healthcare utilisation. Secondary outcomes include various physiological measures. Cost-effectiveness analysis will also be performed. The outcomes will be measured by questionnaires at baseline, after 6, 12, and 24 months, and sickness absence will be obtained from the employer's registers.</p> <p>Discussion</p> <p>No trials are yet available that have evaluated the effectiveness of daily physical activity monitoring and distance counselling in an occupational health setting over a 12 month period and no data on cost-effectiveness of such intervention are available.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT00994565</p

Excitability and Synaptic Alterations in the Cerebellum of APP/PS1 Mice

In Alzheimer's disease (AD), the severity of cognitive symptoms is better correlated with the levels of soluble amyloid-beta (Aβ) rather than with the deposition of fibrillar Aβ in amyloid plaques. In APP/PS1 mice, a murine model of AD, at 8 months of age the cerebellum is devoid of fibrillar Aβ, but dosage of soluble Aβ1–42, the form which is more prone to aggregation, showed higher levels in this structure than in the forebrain. Aim of this study was to investigate the alterations of intrinsic membrane properties and of synaptic inputs in Purkinje cells (PCs) of the cerebellum, where only soluble Aβ is present. PCs were recorded by whole-cell patch-clamp in cerebellar slices from wild-type and APP/PS1 mice. In APP/PS1 PCs, evoked action potential discharge showed enhanced frequency adaptation and larger afterhyperpolarizations, indicating a reduction of the intrinsic membrane excitability. In the miniature GABAergic postsynaptic currents, the largest events were absent in APP/PS1 mice and the interspike intervals distribution was shifted to the left, but the mean amplitude and frequency were normal. The ryanodine-sensitive multivescicular release was not altered and the postsynaptic responsiveness to a GABAA agonist was intact. Climbing fiber postsynaptic currents were normal but their short-term plasticity was reduced in a time window of 100–800 ms. Parallel fiber postsynaptic currents and their short-term plasticity were normal. These results indicate that, in the cerebellar cortex, chronically elevated levels of soluble Aβ1–42 are associated with alterations of the intrinsic excitability of PCs and with alterations of the release of GABA from interneurons and of glutamate from climbing fibers, while the release of glutamate from parallel fibers and all postsynaptic mechanisms are preserved. Thus, soluble Aβ1–42 causes, in PCs, multiple functional alterations, including an impairment of intrinsic membrane properties and synapse-specific deficits, with differential consequences even in different subtypes of glutamatergic synapses

Use of Carboxymethyl Cellulose and Collagen Carrier with Equine Bone Lyophilisate Suggests Late Onset Bone Regenerative Effect in a Humerus Drill Defect – A Pilot Study in Six Sheep

We assessed the use of a filler compound together with the osteoinductive demineralized bone matrix (DBM), Colloss E. The filler was comprised of carboxymethyl-cellulose and collagen type 1. The purpose of the study was to see if the filler compound would enhance the bone formation and distribute the osteoinductive stimulus throughout the bone defect. Six sheep underwent a bilateral humerus drill defect. The drill hole was filled with a compound consisting of 100 mg CMC, 100 mg collagen powder, and 1 ccm autologous full blood in one side, and a combination of this filler compound and 20 mg Colloss E in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (µCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site was calculated with both QCT and µCT. Bone volume to total volume (BV/TV) was analyzed using µCT and histomorphometry. Although not statistically significant, results showed increased bone BMD after 16 weeks in µCT data and an increased BV/TV after 16 weeks in both µCT and histology. Correlation between QCT and µCT was R2 = 0.804. Correlation between histomorphometry and µCT BV/TV data was R2 = 0.8935 and with an average overrepresentation of 8.2% in histomorphometry. In conclusion the CMC-Collagen + Colloss E filler seems like a viable osteogenic bone filler mid- to long term. A correlation was found between the analytical methods used in this study