Strengthening and stretching for rheumatoid arthritis of the hand (SARAH). A randomised controlled trial and economic evaluation

Study registration: Current Controlled Trials ISRCTN 89936343.Background - The effectiveness of exercise for improving hand and wrist function in people with rheumatoid arthritis (RA) is uncertain. Objectives - The study aims were (1) to estimate the clinical effectiveness and cost-effectiveness of adding an optimised exercise programme for hands and upper limbs to standard care for patients with RA; and (2) to qualitatively describe the experience of participants in the trial with a particular emphasis on acceptability of the intervention, exercise behaviours and reasons for adherence/non-adherence.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 19. See the NIHR Journals Library website for further project information. This report has been developed in association with the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford and the NIHR Biomedical Research Unit Funding Scheme. This project benefited from facilities funded through Birmingham Science City Translational Medicine Clinical Research and Infrastructure Trials Platform, with support from Advantage West Midlands

Template for Developing Guidelines for the Evaluation of the Clinical Efficacy of Psychophysiological Interventions

An essential function of both the Association for Applied Psychophysiology and Biofeedback (AAPB) and the Society for Neuronal Regulation (SNR) is the systematic evaluation of psychophysiological interventions that have been developed for the treatment of medical and psychiatric disorders. In order to address scientific concerns regarding the efficacy of specific clinical applications of biofeedback, these two societies formed and Efficacy Task Force. The process to be used in the assessment of treatment efficacy, specificity and clinical utility is presented in the form of a template that will serve as the foundation for a series of scientific reviews and practice guidlines to be published by both societies

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

Bio/neurofeedback

ResumenLas técnicas de biofeedback (BF) desarrolladas desde los años 60 por la psicología tienen ya una larga historia, en la que han demostrado su utilidad y eficacia terapéutica en una considerable variedad de trastornos clínicos: neurológicos, neuromusculares, cardiovasculares, gastrointestinales, dolores crónicos, problemas dermatológicos, de sueño, respiratorios, trastornos traumáticos y de estrés, entre muchos otros. Entre las aplicaciones prácticas del BF destaca de modo especial el biofeedback electroencefalográfico (BF-EEG), denominado neurofeedback (NF), cuya importancia y aplicaciones clínicas ha crecido y continua creciendo aceleradamente gracias al importante desarrollo acaecido en los campos de la neurociencia y la informática sobre los que se sustenta el NF. El trabajo presentado describe y analiza de forma práctica el proceso y la técnica del BF y del NF, además de sus fundamentos metodológicos, pero, sobre todo, examina desde un punto de vista crítico las principales aplicaciones clínicas de las mismas junto al nivel de utilidad y eficacia terapéutica alcanzado en la actualidad.AbstractBiofeedback (BF) techniques were developed by psychology in the 1960s having then a long history in which they have proved their usefulness and therapeutic efficacy in a considerable variety of clinical disorders: neurologic, neuromuscular, cardiovascular, gastrointestinal, chronic pain, dermatological, sleep, respiratory, trauma and stress, among many other disorders. Practical applications of the BF include in particular Electroencephalographic Biofeedback (BF-EEG), known as Neurofeedback (NF), whose importance and clinical applications have grown and continue to grow rapidly thanks to the significant development in the fields of neuroscience and computer science on which NF rests. This paper describes and analyzes the technique and process of BF and NF, apart from their methodological foundations but, above all, from a critical point of view, the paper examines their main clinical applications together with the level of utility and therapeutic effectiveness currently achieved

Fumonisin B1 Toxicity in Grower-Finisher Pigs: A Comparative Analysis of Genetically Engineered Bt Corn and non-Bt Corn by Using Quantitative Dietary Exposure Assessment Modeling

In this study, we investigate the long-term exposure (20 weeks) to fumonisin B1 (FB1) in grower-finisher pigs by conducting a quantitative exposure assessment (QEA). Our analytical approach involved both deterministic and semi-stochastic modeling for dietary comparative analyses of FB1 exposures originating from genetically engineered Bacillus thuringiensis (Bt)-corn, conventional non-Bt corn and distiller’s dried grains with solubles (DDGS) derived from Bt and/or non-Bt corn. Results from both deterministic and semi-stochastic demonstrated a distinct difference of FB1 toxicity in feed between Bt corn and non-Bt corn. Semi-stochastic results predicted the lowest FB1 exposure for Bt grain with a mean of 1.5 mg FB1/kg diet and the highest FB1 exposure for a diet consisting of non-Bt grain and non-Bt DDGS with a mean of 7.87 mg FB1/kg diet; the chronic toxicological incipient level of concern is 1.0 mg of FB1/kg of diet. Deterministic results closely mirrored but tended to slightly under predict the mean result for the semi-stochastic analysis. This novel comparative QEA model reveals that diet scenarios where the source of grain is derived from Bt corn presents less potential to induce FB1 toxicity than diets containing non-Bt corn

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Tumor Phyllodes de la mama

 Introduction Phyllodes tumor (PT) is a rare tumor of the breast, representing less than 1% of all breast neoplasms (1) and 2 to 3% of fibroepithelial tumors (7). This neoplasm is classified as: Benign PT, Borderline PT and Malignant PT (Norris and Taylor-WHO) (9). Objective To carry out a review about the diagnosis and treatment of phyllodes tumor. Development PTs are fibroepithelial neoplasms that according to stromal cellularity, nuclear atypia, mitotic rate, heterologous elements are classified as: benign, borderline and malignant (1). The maximum incidence occurs between 35-55 years. Imaging diagnosis is based on the use of mammography, ultrasound, magnetic resonance imaging and radioguided core biopsy. Optimal surgical management is the fundamental tool in PT. There is controversy about the use of adjuvant treatment with radiotherapy and chemotherapy. Conclusions: PT is a benign neoplasm of the breast, surgery is the treatment of choice. The free edge greater than 1 cm recommended by the NCCN is predictive of a lower percentage of local recurrence. Complementary treatments with radiotherapy and chemotherapy are controversial. Introducción: El tumor phyllodes (TP) es un tumor raro de la mama, representa menos del 1% de todas las neoplasias de la mama (1) y el 2 a 3 % de los tumores fibroepiteliales (7). Esta neoplasia se clasifica en: TP Benigno, TP Borderline y TP Maligno (Norris y Taylor-OMS) (9). Objetivo: Realizar una revisión acerca del diagnóstico y tratamiento del tumor phyllodes. Desarrollo: Los TP son neoplasias fibroepiteliales qué de acuerdo a la celularidad estromal, atipia nuclear, tasa mitótica, elementos heterólogos son clasificados como: benignos, borderline y malignos (1). La máxima incidencia se da entre los 35-55 años. El diagnóstico por imágenes se basa en el uso de mamografía, ecografía, resonancia magnética y biopsia core radioguiada. El óptimo manejo quirúrgico constituye la herramienta fundamental en TP. Existe controversia acerca del uso de tratamiento adyuvante con radioterapia y quimioterapia.  Conclusiones: TP es una neoplasia benigna de la mama, la cirugía es el tratamiento de elección. El borde libre mayor de 1 cm recomendado por la NCCN es predictivo para un menor porcentaje de recurrencia local. Los tratamientos complementarios con radioterapia y quimioterapia son controversiales

Representation and misrepresentation of scientific evidence in contemporary tobacco regulation:a review of tobacco industry submissions to the UK Government consultation on standardised packaging

BACKGROUND: Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. METHODS AND FINDINGS: We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. CONCLUSIONS: The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation, particularly stakeholder consultation, provide an opportunity for highly resourced corporations to slow, weaken, or prevent public health policies

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

The p53 codon 72 proline allele is endowed with enhanced cell-death inducing potential in cancer cells exposed to hypoxia

The preferential retention of the arginine allele at the p53 codon 72 locus is commonly observed in tumours from arginine/proline heterozygotes. Considering that cancer cells are harboured in a hypoxic environment in vivo, we here tested the hypothesis that the p53 codon 72 proline allele confers a survival disadvantage in presence of hypoxia. Here, we show that the transient transfection of the proline allele in p53 null cancer cells exposed to low oxygen tension or to the hypoxia-mimetic drug Desferoxamine induces a higher amount of cell death than the arginine allele. Accordingly, proline allele transiently transfected cell lines express lower levels of hypoxia pro-survival genes (HIF-1α, carbonic anhydrase IX, vascular endothelial growth factor, heme oxygenase-I, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2), compared to those transiently transfected with the arginine allele. Further, we report that the exposure of the arginine/proline heterozygote MCF-7 breast cancer cell line to cytotoxic concentration of Desferoxamine for several weeks, gives raise to hypoxia-resistant clones, carrying the arginine, but not the proline allele. These data indicate that the p53 codon 72 proline allele is less permissive for the growth of cancer cells in a hypoxic environment, and suggest that the preferential retention of the arginine allele in the tumour tissues of arginine/proline heterozygous patients may depend upon its lowered capacity to induce cell death in a hypoxic tumour environment