Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Barriers and motivators to gaining access to smoking cessation services amongst deprived smokers – a qualitative study

BACKGROUND: Smoking is strongly associated with disadvantage and is an important contributor to inequalities in health. Smoking cessation services have been implemented in the UK targeting disadvantaged smokers, but there is little evidence available on how to design services to attract this priority group. METHODS: We conducted focus groups with 39 smokers aged 21–75 from the most socio-economically deprived areas of Nottingham UK who had made an unsuccessful attempt to quit within the last year without using smoking cessation services, to identify specific barriers or motivators to gaining access to these services. RESULTS: Barriers to use of existing services related to fear of being judged, fear of failure, a perceived lack of knowledge about existing services, a perception that available interventions – particularly Nicotine Replacement Therapy – are expensive and ineffective, and negative media publicity about bupropion. Participants expressed a preference for a personalised, non-judgemental approach combining counselling with affordable, accessible and effective pharmacological therapies; convenient and flexible timing of service delivery, and the possibility of subsidised complementary therapies. CONCLUSION: We conclude that smokers from these deprived areas generally had low awareness of the services available to help them, and misconceptions about their availability and effectiveness. A more personalised approach to promoting services that are non-judgemental, and with free pharmacotherapy and flexible support may encourage more deprived smokers to quit smoking

Amniotic Epithelial Cells from the Human Placenta Potently Suppress a Mouse Model of Multiple Sclerosis

Human amniotic epithelial cells (hAEC) have stem cell-like features and immunomodulatory properties. Here we show that hAEC significantly suppressed splenocyte proliferation in vitro and potently attenuated a mouse model of multiple sclerosis (MS). Central nervous system (CNS) CD3+ T cell and F4/80+ monocyte/macrophage infiltration and demyelination were significantly reduced with hAEC treatment. Besides the known secretion of prostaglandin E2 (PGE2), we report the novel finding that hAEC utilize transforming growth factor-β (TGF-β) for immunosuppression. Neutralization of TGF-β or PGE2 in splenocyte proliferation assays significantly reduced hAEC-induced suppression. Splenocytes from hAEC-treated mice showed a Th2 cytokine shift with significantly elevated IL-5 production. While transferred CFSE-labeled hAEC could be detected in the lung, none were identified in the CNS or in lymphoid organs. This is the first report documenting the therapeutic effect of hAEC in a MS-like model and suggest that hAEC may have potential for use as therapy for MS

HSV Neutralization by the Microbicidal Candidate C5A

Genital herpes is a major risk factor in acquiring human immunodeficiency virus type-1 (HIV-1) infection and is caused by both Herpes Simplex virus type 1 (HSV-1) and HSV-2. The amphipathic peptide C5A, derived from the non-structural hepatitis C virus (HCV) protein 5A, was shown to prevent HIV-1 infection but neither influenza nor vesicular stomatitis virus infections. Here we investigated the antiviral function of C5A on HSV infections. C5A efficiently inhibited both HSV-1 and HSV-2 infection in epithelial cells in vitro as well as in an ex vivo epidermal infection model. C5A destabilized the integrity of the viral HSV membrane. Furthermore, drug resistant HSV strains were inhibited by this peptide. Notably, C5A-mediated neutralization of HSV-1 prevented HIV-1 transmission. An in vitro HIV-1 transmigration assay was developed using primary genital epithelial cells and HSV infection increased HIV-1 transmigration. Treatment with C5A abolished HIV-1 transmigration by preventing HSV infection and by preserving the integrity of the genital epithelium that was severely compromised by HSV infection. In conclusion, this study demonstrates that C5A represents a multipurpose microbicide candidate, which neutralizes both HIV-1 and HSV, and which may interfere with HIV-1 transmission through the genital epithelium

Do differences in understory light contribute to species distributions along a tropical rainfall gradient?

In tropical forests, regional differences in annual rainfall correlate with differences in plant species composition. Although water availability is clearly one factor determining species distribution, other environmental variables that covary with rainfall may contribute to distributions. One such variable is light availability in the understory, which decreases towards wetter forests due to differences in canopy density and phenology. We established common garden experiments in three sites along a rainfall gradient across the Isthmus of Panama in order to measure the differences in understory light availability, and to evaluate their influence on the performance of 24 shade-tolerant species with contrasting distributions. Within sites, the effect of understory light availability on species performance depended strongly on water availability. When water was not limiting, either naturally in the wetter site or through water supplementation in drier sites, seedling performance improved at higher light. In contrast, when water was limiting at the drier sites, seedling performance was reduced at higher light, presumably due to an increase in water stress that affected mostly wet-distribution species. Although wetter forest understories were on average darker, wet-distribution species were not more shade-tolerant than dry-distribution species. Instead, wet-distribution species had higher absolute growth rates and, when water was not limiting, were better able to take advantage of small increases in light than dry-distribution species. Our results suggest that in wet forests the ability to grow fast during temporary increases in light may be a key trait for successful recruitment. The slower growth rates of the dry-distribution species, possibly due to trade-offs associated with greater drought tolerance, may exclude these species from wetter forests

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio

High plasma uric acid concentration: causes and consequences

High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides) in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease

Measurement of b hadron lifetimes in exclusive decays containing a J/psi in p-pbar collisions at sqrt(s)=1.96TeV

We report on a measurement of $b$-hadron lifetimes in the fully reconstructed decay modes B^+ -->J/Psi K+, B^0 --> J/Psi K*, B^0 --> J/Psi Ks, and Lambda_b --> J/Psi Lambda using data corresponding to an integrated luminosity of 4.3 ${\rm fb}^{-1}$, collected by the CDF II detector at the Fermilab Tevatron. The measured lifetimes are $\tau$B^+ = $1.639 \pm 0.009 ({\rm stat}) \pm 0.009 {\rm (syst) ~ ps}$, $\tau$B^0 = $1.507 \pm 0.010 ({\rm stat}) \pm 0.008 {\rm (syst) ~ ps}$ and $\tau$Lambda_b = $1.537 \pm 0.045 ({\rm stat}) \pm 0.014 {\rm (syst) ~ ps}$. The lifetime ratios are $\tau$B^+/$\tau$B^0 = $1.088 \pm 0.009 ({\rm stat})\pm 0.004 ({\rm syst})$ and $\tau$Lambda_b/$\tau$B^0 = $1.020 \pm 0.030 ({\rm stat})\pm 0.008 ({\rm syst})$. These are the most precise determinations of these quantities from a single experiment.Comment: revised version. accepted for PRL publicatio