Methodological considerations for studies in sport and exercise science with women as participants: a working guide for standards of practice for research on women

Until recently, there has been less demand for and interest in female-specific sport and exercise science data. As a result, the vast majority of high-quality sport and exercise science data have been derived from studies with men as participants, which reduces the application of these data due to the known physiological differences between the sexes, specifically with regard to reproductive endocrinology. Furthermore, a shortage of specialist knowledge on female physiology in the sport science community, coupled with a reluctance to effectively adapt experimental designs to incorporate female-specific considerations, such as the menstrual cycle, hormonal contraceptive use, pregnancy and the menopause, has slowed the pursuit of knowledge in this field of research. In addition, a lack of agreement on the terminology and methodological approaches (i.e., gold-standard techniques) used within this research area has further hindered the ability of researchers to adequately develop evidenced-based guidelines for female exercisers. The purpose of this paper was to highlight the specific considerations needed when employing women (i.e., from athletes to non-athletes) as participants in sport and exercise science-based research. These considerations relate to participant selection criteria and adaptations for experimental design and address the diversity and complexities associated with female reproductive endocrinology across the lifespan. This statement intends to promote an increase in the inclusion of women as participants in studies related to sport and exercise science and an enhanced execution of these studies resulting in more high-quality female-specific data

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

Comparison of (semi-)automatic and manually adjusted measurements of left ventricular function in dual source computed tomography using three different software tools

To assess the accuracy of (semi-)automatic measurements of left ventricular (LV) functional parameters in cardiac dual-source computed tomography (DSCT) compared to manually adjusted measurements in three different workstations. Forty patients, who underwent cardiac DSCT, were included (31 men, mean age 58 ± 14 years). Multiphase reconstructions were made with ten series at every 10% of the RR-interval. LV function analysis was performed on three different, commercially available workstations. On all three workstations, end-systolic volume (ESV), end-diastolic volume (EDV), LV ejection fraction (LVEF) and myocardial mass (MM) were calculated as automatically as possible. With the same DSCT datasets, LV functional parameters were also calculated with as many manual adjustments as needed for accurate assessment for all three software tools. For both semi-automatic as well as manual methods, time needed for evaluation was recorded. Paired t-tests were employed to calculate differences in LV functional parameters. Repeated measurements were performed to determine intra-observer and inter-observer variability. (Semi-)automatic measurements revealed a good correlation with manually adjusted measurements for Vitrea (LVEF r = 0.93, EDV r = 0.94, ESV r = 0.98 and MM r = 0.94) and Aquarius (LVEF r = 0.96, EDV r = 0.94, ESV r = 0.98 and MM r = 0.96). Also, good correlation was obtained for Circulation, except for LVEF (LVEF r = 0.45, EDV r = 0.93, ESV r = 0.92 and MM r = 0.86). However, statistically significant differences were found between (semi-)automatically and manually adjusted measurements for LVEF (P < 0.05) and ESV (P < 0.001) in Vitrea, all LV functional parameters in Circulation (P < 0.001) and EDV, ESV and MM (<0.001) in Aquarius Workstation. (Semi-)automatic measurement of LV functional parameters is feasible, but significant differences were found for at least two different functional parameters in all three workstations. Therefore, expert manual correction is recommended at all times

A predictive score to identify hospitalized patients' risk of discharge to a post-acute care facility

<p>Abstract</p> <p>Background</p> <p>Early identification of patients who need post-acute care (PAC) may improve discharge planning. The purposes of the study were to develop and validate a score predicting discharge to a post-acute care (PAC) facility and to determine its best assessment time.</p> <p>Methods</p> <p>We conducted a prospective study including 349 (derivation cohort) and 161 (validation cohort) consecutive patients in a general internal medicine service of a teaching hospital. We developed logistic regression models predicting discharge to a PAC facility, based on patient variables measured on admission (day 1) and on day 3. The value of each model was assessed by its area under the receiver operating characteristics curve (AUC). A simple numerical score was derived from the best model, and was validated in a separate cohort.</p> <p>Results</p> <p>Prediction of discharge to a PAC facility was as accurate on day 1 (AUC: 0.81) as on day 3 (AUC: 0.82). The day-3 model was more parsimonious, with 5 variables: patient's partner inability to provide home help (4 pts); inability to self-manage drug regimen (4 pts); number of active medical problems on admission (1 pt per problem); dependency in bathing (4 pts) and in transfers from bed to chair (4 pts) on day 3. A score ≥ 8 points predicted discharge to a PAC facility with a sensitivity of 87% and a specificity of 63%, and was significantly associated with inappropriate hospital days due to discharge delays. Internal and external validations confirmed these results.</p> <p>Conclusion</p> <p>A simple score computed on the 3rd hospital day predicted discharge to a PAC facility with good accuracy. A score > 8 points should prompt early discharge planning.</p

Using Ribosomal Protein Genes as Reference: A Tale of Caution

Background: Housekeeping genes are needed in every tissue as their expression is required for survival, integrity or duplication of every cell. Housekeeping genes commonly have been used as reference genes to normalize gene expression data, the underlying assumption being that they are expressed in every cell type at approximately the same level. Often, the terms "reference genes'' and "housekeeping genes'' are used interchangeably. In this paper, we would like to distinguish between these terms. Consensus is growing that housekeeping genes which have traditionally been used to normalize gene expression data are not good reference genes. Recently, ribosomal protein genes have been suggested as reference genes based on a meta-analysis of publicly available microarray data. Methodology/Principal Findings: We have applied several statistical tools on a dataset of 70 microarrays representing 22 different tissues, to assess and visualize expression stability of ribosomal protein genes. We confirmed the housekeeping status of these genes, but further estimated expression stability across tissues in order to assess their potential as reference genes. One- and two-way ANOVA revealed that all ribosomal protein genes have significant expression variation across tissues and exhibit tissue-dependent expression behavior as a group. Via multidimensional unfolding analysis, we visualized this tissue-dependency. In addition, we explored mechanisms that may cause tissue dependent effects of individual ribosomal protein genes. Conclusions/Significance: Here we provide statistical and biological evidence that ribosomal protein genes exhibit important tissue-dependent variation in mRNA expression. Though these genes are most stably expressed of all investigated genes in a meta-analysis they cannot be considered true reference genes

Cd2+ Toxicity to a Green Alga Chlamydomonas reinhardtii as Influenced by Its Adsorption on TiO2 Engineered Nanoparticles

In the present study, Cd2+ adsorption on polyacrylate-coated TiO2 engineered nanoparticles (TiO2-ENs) and its effect on the bioavailability as well as toxicity of Cd2+ to a green alga Chlamydomonas reinhardtii were investigated. TiO2-ENs could be well dispersed in the experimental medium and their pHpzc is approximately 2. There was a quick adsorption of Cd2+ on TiO2-ENs and a steady state was reached within 30 min. A pseudo-first order kinetics was found for the time-related changes in the amount of Cd2+ complexed with TiO2-ENs. At equilibrium, Cd2+ adsorption followed the Langmuir isotherm with the maximum binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO2-EN concentration was 1, 10, and 100 mg/l, respectively. On the other hand, Cd2+ toxicity was alleviated in the presence of TiO2-ENs. Algal growth was less suppressed in treatments with comparable total Cd2+ concentration but more TiO2-ENs. However, such toxicity difference disappeared and all the data points could be fitted to a single Logistic dose-response curve when cell growth inhibition was plotted against the free Cd2+ concentration. No detectable amount of TiO2-ENs was found to be associated with the algal cells. Therefore, TiO2-ENs could reduce the free Cd2+ concentration in the toxicity media, which further lowered its bioavailability and toxicity to C. reinhardtii

The combined effects of obesity, abdominal obesity and major depression/anxiety on health-related quality of life: The lifelines cohort study

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Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300

An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible “parental” strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a “stealth” strategy to evade detection by the host immune system

Neutrophil-guided dosing of anthracycline–cyclophosphamide-containing chemotherapy in patients with breast cancer: a feasibility study

The aim of this study was to investigate whether neutrophil-guided dose escalation of anthracycline–cyclophosphamide-containing chemotherapy (ACC) for breast cancer is feasible, in order to optimize outcome. Breast cancer patients planned for 3-weekly ACC were enrolled in this study. The first treatment cycle was administered in a standard BSA-adjusted dose. The absolute neutrophil count was measured at baseline and at day 8, 11 and 15 after administration of ACC. For patients with none or mild (CTC grade 0–2) neutropenia and no other dose-limiting toxicity, we performed a 10–25 % dose escalation of the second cycle with the opportunity to a further 10–25 % dose escalation of the third cycle. Thirty patients were treated in the adjuvant setting with either FE100C (n = 23) or AC (n = 4), or in the palliative setting with FAC (n = 3). Two out of 23 patients (9 %) treated with FEC did not develop grade 3–4 neutropenia after the first treatment cycle. Dose escalation was performed in these two patients (30 % in one and 15 % in the other patient). During dose escalation, there were no complications like febrile neutropenia. No patients treated with FAC or AC could be escalated, since all of them developed grade 3–4 neutropenia. We conclude that asymptomatic grade 3–4 neutropenia is likely to be achieved in the majority of patients with breast cancer treated with ACC according to presently advocated BSA-based dose levels. Escalation of currently advocated ACC doses without G-CSF, with a target of grade 3–4 neutropenia, is feasible, but only possible in a small proportion of patients. EudraCT 2010-020309-33