Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate-Severe Copd: Results of a Randomized, Double-Blind Clinical Study

OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1AUC*0-1 h).DESIGN: A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.SETTING: Five centres in four countries -- one centre each in France, Greece and Italy, and two centres in the Netherlands.PATIENTS: Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV11.17 L (range 0.56 to 1.77 L).INTERVENTIONS: Patients inhaled single doses of formoterol dry powder (12 and 24 μg), single doses of salmeterol (50 and 100 μg) and matching placebo on five separate days.MAIN RESULTS: The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1AUC*0-1 h, showed that formoterol 12 μg was statistically significantly superior to salmeterol 50 μg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol.CONCLUSIONS: Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD

Erratum to: CASPER plus (CollAborative care in screen-positive EldeRs with major depressive disorder): study protocol for a randomised controlled trial

Published onlinePUBLISHED ERRATUMThe original article is available at http://hdl.handle.net/10871/18985.n/

Cross-cultural adaptation and determination of the reliability and validity of PRTEE-S (Patientskattad Utvärdering av Tennisarmbåge), a questionnaire for patients with lateral epicondylalgia, in a Swedish population

<p>Abstract</p> <p>Background</p> <p>In Sweden, as well as in Scandinavia, there is no easy way to evaluate patients' difficulties when they suffer from lateral epicondylitis/epicondylalgia. However, there is a Canadian questionnaire, in English, that could make the evaluation of a patient's pain and functional loss both quick and inexpensive. Therefore, the aim of this study was to translate and cross-culturally adapt the questionnaire "Patient-rated Tennis Elbow Evaluation" into Swedish (PRTEE-S; "Patientskattad Utvärdering av Tennisarmbåge"), and to evaluate the reliability and validity of the test.</p> <p>Methods</p> <p>The Patient-rated Tennis Elbow Evaluation was cross-culturally adapted for the Swedish language according to well-established guidelines. Fifty-four patients with unilateral epicondylitis/epicondylalgia were assessed using the PRTEE-S (Patientskattad Utvärdering av Tennisarmbåge), the Disabilities of Arm, Shoulder, and Hand questionnaire, and the Roles & Maudsley score to establish the validity and reliability of the PRTEE-S. Reliability was determined via calculation of the intra-class correlation coefficient (ICC) the internal consistency was assessed by Cronbach's alpha, and validity was calculated using Spearman's correlation coefficient.</p> <p>Results</p> <p>The test-retest reliability, using the PRTEE-S (Patientskattad Utvärdering av Tennisarmbåge) intraclass correlation coefficient, was 0.95 and the internal consistency was 0.94. The PRTEE-S correlated well with the Disabilities of the Arm, Shoulder, and Hand questionnaire (r = 0.88) and the Roles & Maudsley score (r = 0.78).</p> <p>Conclusion</p> <p>The PRTEE-S (Patientskattad Utvärdering av Tennisarmbåge) represents a reliable and valid instrument to evaluate the subjective outcome in Swedish speaking patients with lateral epicondylitis/epicondylalgia, and can be used in both research and clinical settings.</p

Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer

The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2–8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock

Microvawe pyrolysis of biomass: control of process parameters for high pyrolysis oil yields and enhanced oil quality

The oil yield and quality of pyrolysis oil from microwave heating of biomass was established by studying the behaviour of Larch in microwave processing. This is the first study in biomass pyrolysis to use a microwave processing technique and methodology that is fundamentally scalable, from which the basis of design for a continuous processing system can be derived to maximise oil yield and quality. It is shown systematically that sample size is a vital parameter that has been overlooked by previous work in this field. When sample size is controlled the liquid product yield is comparable to conventional pyrolysis, and can be achieved at an energy input of around 600 kWh/t. The quality of the liquid product is significantly improved compared to conventional pyrolysis processes, which results from the very rapid heating and quenching that can be achieved with microwave processing. The yields of Levoglucosan and phenolic compounds were found to be an order of magnitude higher in microwave pyrolysis when compared with conventional fast pyrolysis. Geometry is a key consideration for the development of a process at scale, and the opportunities and challenges for scale-up are discussed within this paper

Lean mass, muscle strength, and physical function in a diverse population of men: a population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Age-related declines in lean body mass appear to be more rapid in men than in women but our understanding of muscle mass and function among different subgroups of men and their changes with age is quite limited. The objective of this analysis is to examine racial/ethnic differences and racial/ethnic group-specific cross-sectional age differences in measures of muscle mass, muscle strength, and physical function among men.</p> <p>Methods</p> <p>Data were obtained from the Boston Area Community Health/Bone (BACH/Bone) Survey, a population-based, cross-sectional, observational survey. Subjects included 1,157 black, Hispanic, and white randomly-selected Boston men ages 30-79 y. Lean mass was assessed by dual-energy x-ray absorptiometry. Upper extremity (grip) strength was assessed with a hand dynamometer and lower extremity physical function was derived from walk and chair stand tests. Upper extremity strength and lower extremity physical function were also indexed by lean mass and lean mass was indexed by the square of height.</p> <p>Results</p> <p>Mean age of the sample was 47.5 y. Substantial cross-sectional age differences in grip strength and physical function were consistent across race/ethnicity. Racial/ethnic differences, with and without adjustment for covariates, were evident in all outcomes except grip strength. Racial differences in lean mass did not translate into parallel differences in physical function. For instance, multivariate modeling (with adjustments for age, height, fat mass, self-rated health and physical activity) indicated that whereas total body lean mass was 2.43 kg (approximately 5%) higher in black compared with white men, black men had a physical function score that was approximately 20% lower than white men.</p> <p>Conclusions</p> <p>In spite of lower levels of lean mass, the higher levels of physical function observed among white compared with non-white men in this study appear to be broadly consistent with known racial/ethnic differences in outcomes.</p

Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member

Modeling CICR in rat ventricular myocytes: voltage clamp studies

<p>Abstract</p> <p>Background</p> <p>The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect <it>Ca</it>²⁺loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR <it>Ca</it>²⁺release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic <it>Ca</it>²⁺concentration ([<it>Ca</it>²⁺]<it>_myo</it>).</p> <p>Methods</p> <p>The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed <it>Ca</it>²⁺channels (trigger-channel and release-channel). It releases <it>Ca</it>²⁺flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[<it>Ca</it>²⁺]<it>_myo</it>.</p> <p>Results</p> <p>Our model reproduces measured VC data published by several laboratories, and generates graded <it>Ca</it>²⁺release at high <it>Ca</it>²⁺gain in a homeostatically-controlled environment where [<it>Ca</it>²⁺]<it>_myo</it>is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR <it>Ca</it>²⁺release, its activation by trigger <it>Ca</it>²⁺, and its refractory characteristics mediated by the luminal SR <it>Ca</it>²⁺sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence <it>Ca</it>²⁺homeostasis.</p> <p>Conclusions</p> <p>We examine the role of the above <it>Ca</it>²⁺regulating mechanisms in handling various types of induced disturbances in <it>Ca</it>²⁺levels by quantifying cellular <it>Ca</it>²⁺balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.</p