Preliminary Experimental Evaluation of a Behavioral-Cognitive Method of Increasing Life Excitement

This randomized controlled trial with 113 adults evaluated the effects of a behavioral-cognitive method developed to increase life excitement. The intervention included encouraging participants to (1) do something new, (2) go somewhere new, (3) act spontaneously, (4) take on a new challenge, (5) learn something new, (6) interact with exciting individuals, (7) engage in romantically or sexually exciting behaviors, (8) read, watch, or listen to something suspenseful or stimulating, (9) take a (reasonable) risk, (10) engage in stimulating exercise or sport, (11) accomplish something new, (12) pursue their own interests, (13) talk with others about exciting experiences, (14) think about past exciting activities, or (15) plan future exciting activities. Participants reported level of excitement-aimed behavior, positive affect, and life satisfaction at pre-intervention and post-intervention. Experimental-group members also reported their outcome levels three months after the end of the intervention. At pre-intervention, excitement-aimed behavior was significantly associated with positive affect and life satisfaction. The intervention had significant between-groups effects on excitement-aimed behavior and positive affect. The experimental group maintained significant pre-post improvements on these variables through a three-month follow-up. The results provide initial support for a new method of increasing positive affect

Detailed SZ study of 19 LoCuSS galaxy clusters: masses and temperatures out to the virial radius

We present 16-GHz AMI SZ observations of 19 clusters with L_X >7x10^37 W (h50=1) selected from the LoCuS survey (0.142<z<0.295) and of A1758b, in the FoV of A1758a. We detect 17 clusters with 5-23sigma peak surface brightnesses. Cluster parameters are obtained using a Bayesian cluster analysis. We fit isothermal beta-models to our data and assume the clusters are virialized (with all the kinetic energy in gas internal energy). Our gas temperature, T_AMI, is derived from AMI SZ data, not from X-ray spectroscopy. Cluster parameters internal to r500 are derived assuming HSE. We find: (i) Different gNFW parameterizations yield significantly different parameter degeneracies. (ii) For h70 = 1, we find the virial radius r200 to be typically 1.6+/-0.1 Mpc and the total mass M_T(r200) typically to be 2.0-2.5xM_T(r500).(iii) Where we have found M_T X-ray (X) and weak-lensing (WL) values in the literature, there is good agreement between WL and AMI estimates (with M_{T,AMI}/M_{T,WL} =1.2^{+0.2}_{-0.3} and =1.0+/-0.1 for r500 and r200, respectively). In comparison, most Suzaku/Chandra estimates are higher than for AMI (with M_{T,X}/M_{T,AMI}=1.7+/-0.2 within r500), particularly for the stronger mergers.(iv) Comparison of T_AMI to T_X sheds light on high X-ray masses: even at large r, T_X can substantially exceed T_AMI in mergers. The use of these higher T_X values will give higher X-ray masses. We stress that large-r T_SZ and T_X data are scarce and must be increased. (v) Despite the paucity of data, there is an indication of a relation between merger activity and SZ ellipticity. (vi) At small radius (but away from any cooling flow) the SZ signal (and T_AMI) is less sensitive to ICM disturbance than the X-ray signal (and T_X) and, even at high r, mergers affect n^2-weighted X-ray data more than n-weighted SZ, implying significant shocking or clumping or both occur even in the outer parts of mergers.Comment: 45 pages, 33 figures, 13 tables Accepted for publication in MNRA

New directions for patient-centred care in scleroderma : the Scleroderma Patient-centred Intervention Network (SPIN)

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc.The initial organisational meeting for SPIN was funded by a Canadian Institutes of Health Research (CIHR) Meetings, Planning, and Dissemination grant to B.D. Thombs (KPE-109130), Sclerodermie Quebec, and the Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, Quebec. SPIN receives finding support from the Sclemderma Society of Ontario, the Scleroderma Society of Canada, and Sclerodermie Quebec. B.D. Thombs and M. Hudson are supported by New Investigator awards from the CIHR, and Etablissement de Jeunes Chercheurs awards from the Fonds de la Recherche en Sante Quebec (FRSQ). M. Baron is the director of the Canadian Scleroderma Research Group, which receives grant folding from the CIHR, the Scleroderma Society of Canada and its provincial chapters, Scleroderma Society of Ontario, Sclerodermie Quebec, and the Ontario Arthritis Society, and educational grants from Actelion Pharmaceuticals and Pfizer. M.D. Mayes and S. Assassi are supported by the NIH/NIAMS Scleroderma Center of Research Translation grant no. P50-AR054144. S.J. Motivala is supported by an NIH career development grant (K23 AG027860) and the UCLA Cousins Center for Psychoneuroimmunology. D. Khanna is supported by a NIH/NIAMS K23 AR053858-04) and NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177), and has served as a consultant or on speakers bureau for Actelion, BMS, Gilead, Pfizer, and United Therapeutics

Matrix Development in Self-Assembly of Articular Cartilage

Articular cartilage is a highly functional tissue which covers the ends of long bones and serves to ensure proper joint movement. A tissue engineering approach that recapitulates the developmental characteristics of articular cartilage can be used to examine the maturation and degeneration of cartilage and produce fully functional neotissue replacements for diseased tissue.This study examined the development of articular cartilage neotissue within a self-assembling process in two phases. In the first phase, articular cartilage constructs were examined at 1, 4, 7, 10, 14, 28, 42, and 56 days immunohistochemically, histologically, and through biochemical analysis for total collagen and glycosaminoglycan (GAG) content. Based on statistical changes in GAG and collagen levels, four time points from the first phase (7, 14, 28, and 56 days) were chosen to carry into the second phase, where the constructs were studied in terms of their mechanical characteristics, relative amounts of collagen types II and VI, and specific GAG types (chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and hyaluronan). Collagen type VI was present in initial abundance and then localized to a pericellular distribution at 4 wks. N-cadherin activity also spiked at early stages of neotissue development, suggesting that self-assembly is mediated through a minimization of free energy. The percentage of collagen type II to total collagen significantly increased over time, while the proportion of collagen type VI to total collagen decreased between 1 and 2 wks. The chondroitin 6- to 4- sulfate ratio decreased steadily during construct maturation. In addition, the compressive properties reached a plateau and tensile characteristics peaked at 4 wks.The indices of cartilage formation examined in this study suggest that tissue maturation in self-assembled articular cartilage mirrors known developmental processes for native tissue. In terms of tissue engineering, it is suggested that exogenous stimulation may be necessary after 4 wks to further augment the functionality of developing constructs

Predictors and correlates for weight changes in patients co-treated with olanzapine and weight mitigating agents; a post-hoc analysis

<p>Abstract</p> <p>Background</p> <p>This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions.</p> <p>Methods</p> <p>Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) ≥ 25 kg/m²who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss ≥ 2 kg and weight gain ≥ 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale.</p> <p>Results</p> <p>Predictors/correlates of weight loss ≥ 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain ≥ 1 kg.</p> <p>Conclusion</p> <p>The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy.</p> <p>Trial Registration</p> <p>This analysis was not a clinical trial and did not involve any medical intervention.</p

Serratia marcescens internalization and replication in human bladder epithelial cells

BACKGROUND: Serratia marcescens, a frequent agent of catheterization-associated bacteriuria, strongly adheres to human bladder epithelial cells in culture. The epithelium normally provides a barrier between lumal organisms and the interstitium; the tight adhesion of bacteria to the epithelial cells can lead to internalization and subsequent lysis. However, internalisation was not shown yet for S. marcescens strains. METHODS: Elektronmicroscopy and the common gentamycin protection assay was used to assess intracellular bacteria. Via site directed mutagenesis, an hemolytic negative isogenic Serratia strain was generated to point out the importance of hemolysin production. RESULTS: We identified an important bacterial factor mediating the internalization of S. marcescens, and lysis of epithelial cells, as the secreted cytolysin ShlA. Microtubule filaments and actin filaments were shown to be involved in internalization. However, cytolysis of eukaryotic cells by ShlA was an interfering factor, and therefore hemolytic-negative mutants were used in subsequent experiments. Isogenic hemolysin-negative mutant strains were still adhesive, but were no longer cytotoxic, did not disrupt the cell culture monolayer, and were no longer internalized by HEp-2 and RT112 bladder epithelial cells under the conditions used for the wild-type strain. After wild-type S. marcescens became intracellular, the infected epithelial cells were lysed by extended vacuolation induced by ShlA. In late stages of vacuolation, highly motile S. marcescens cells were observed in the vacuoles. S. marcescens was also able to replicate in cultured HEp-2 cells, and replication was not dependent on hemolysin production. CONCLUSION: The results reported here showed that the pore-forming toxin ShlA triggers microtubule-dependent invasion and is the main factor inducing lysis of the epithelial cells to release the bacteria, and therefore plays a major role in the development of S. marcescens infections

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation

Incisional hernia following colorectal cancer surgery according to suture technique: Hughes Abdominal Repair Randomized Trial (HART).

BACKGROUND: Incisional hernias cause morbidity and may require further surgery. HART (Hughes Abdominal Repair Trial) assessed the effect of an alternative suture method on the incidence of incisional hernia following colorectal cancer surgery. METHODS: A pragmatic multicentre single-blind RCT allocated patients undergoing midline incision for colorectal cancer to either Hughes closure (double far-near-near-far sutures of 1 nylon suture at 2-cm intervals along the fascia combined with conventional mass closure) or the surgeon's standard closure. The primary outcome was the incidence of incisional hernia at 1 year assessed by clinical examination. An intention-to-treat analysis was performed. RESULTS: Between August 2014 and February 2018, 802 patients were randomized to either Hughes closure (401) or the standard mass closure group (401). At 1 year after surgery, 672 patients (83.7 per cent) were included in the primary outcome analysis; 50 of 339 patients (14.8 per cent) in the Hughes group and 57 of 333 (17.1 per cent) in the standard closure group had incisional hernia (OR 0.84, 95 per cent c.i. 0.55 to 1.27; P = 0.402). At 2 years, 78 patients (28.7 per cent) in the Hughes repair group and 84 (31.8 per cent) in the standard closure group had incisional hernia (OR 0.86, 0.59 to 1.25; P = 0.429). Adverse events were similar in the two groups, apart from the rate of surgical-site infection, which was higher in the Hughes group (13.2 versus 7.7 per cent; OR 1.82, 1.14 to 2.91; P = 0.011). CONCLUSION: The incidence of incisional hernia after colorectal cancer surgery is high. There was no statistical difference in incidence between Hughes closure and mass closure at 1 or 2 years. REGISTRATION NUMBER: ISRCTN25616490 (http://www.controlled-trials.com)