Early Eukaryotes in the Lakhanda Biota (Mesoproterozoic, Southeastern Siberia)-Morphological and Geochemical Evidence.

The Mesoproterozoic Lakhanda Group (~1030 Ma) preserves one of the most diverse communities of pre-Ediacaran eukaryotes. More precisely, the Lakhanda Biota includes more than twenty taxa that have been assigned to eukaryotes with different degrees of confidence. Eight of these taxa meet current criteria for the identification of eukaryotic fossils in ancient records. These include previously described fossils such as ornamented acritarchs (Valeria lophostriata, Trachyhystrichosphaera aimika), filamentous coenocytic organisms (Aimonema ramosa, Palaeovaucheria clavata), as well as fossils with smooth-walled envelopes and single outgrowth structures (Caudosphaera expansa, Germinosphaera bispinosa, and Jacutianema solubila). In addition to these, we found as yet undescribed fossils which share remarkable similarities with Ourasphaira giraldae, a possible higher fungi species known from the (?) Meso- to Neoproterozoic of Arctic Canada. Regardless of the exact systematic affinity, these fossils can confidently be assigned to eukaryotes because of the size and high morphological complexity. Intriguingly, the organic record of the Lakhanda Formation lacks biomarkers indicative of eukaryotes (that is, regular steranes). This finding would be in line with the idea that eukaryotes were present but not significant in Mesoproterozoic marine ecosystems. However, preliminary data from an ongoing study indicate an advanced thermal maturity of the organic matter, emphasizing that this conclusion might not be drawn with absolute confidence.

Role of sports psychology and sports nutrition in return to play from musculoskeletal injuries in professional soccer: an interdisciplinary approach.

Musculoskeletal injuries are prevalent in professional soccer and can result in lost training time or match play. It is intuitive that the "return to play" (RTP) pathway will depend, in large part, on the expertise of sports medicine practitioners (e.g. surgeons, physicians, physiotherapists) responsible for player's recovery. Consensus statements on returning athletes to sport following injury acknowledge the contributions of sport psychology and sports nutrition. However, specific consideration on how to integrate these two recognized - but often overlooked components of injury rehabilitation - into existing sport medicine approaches has yet to be examined. Using a framework of milestones directed by the medical physician and physical trainer, the evidence is summarized and suggestions provided on the integration of sports psychology and sports nutrition into an interdisciplinary RTP approach. We examine recovery from a phase approach (acute injury and functional recovery) to highlight interdisciplinary opportunities in the management of musculoskeletal soccer injuries. An interdisciplinary approach is understood to achieve outcomes that could not be achieved within the framework of a single discipline. The incorporation of sports psychology and nutrition theoretically compliment milestones used in current medically-based RTP models. Our hope is that this article serves as a catalyst for interdisciplinary practice and research - not only in sports nutrition and sports psychology - but across all sport and exercise disciplines.

Hippocampal subfield pathologic burden in Lewy body diseases vs. Alzheimer's disease.

AIMS: Lewy body diseases (LBD) are characterized by alpha-synuclein (SYN) pathology, but comorbid Alzheimer's disease (AD) pathology is common and the relationship between these pathologies in microanatomic hippocampal subfields is understudied. Here we use digital histological methods to test the association between hippocampal SYN pathology and the distribution of tau and amyloid-beta (Aß) pathology in LBD and contrast with AD subjects. We also correlate pathologic burden with antemortem episodic memory testing. METHODS: Hippocampal sections from 49 autopsy-confirmed LBD cases, 30 with no/low AD copathology (LBD - AD) and 19 with moderate/severe AD copathology (LBD + AD), and 30 AD patients were stained for SYN, tau, and Aß. Sections underwent digital histological analysis of subfield pathological burden which was correlated with antemortem memory testing. RESULTS: LBD - AD and LBD + AD had similar severity and distribution of SYN pathology (P > 0.05), CA2/3 being the most affected subfield (P < 0.02). In LBD, SYN correlated with tau across subfields (R = 0.49, P < 0.001). Tau burden was higher in AD than LBD + AD (P < 0.001), CA1/subiculum and entorhinal cortex (ERC) being most affected regions (P = 0.04 to <0.01). However, tau pathology in LBD - AD was greatest in CA2/3, which was equivalent to LBD + AD. Aß severity and distribution was similar between LBD + AD and AD. Total hippocampal tau and CA2/3 tau was inversely correlated with memory performance in LBD (R = -0.52, -0.69, P = 0.04, 0.009). CONCLUSIONS: Our findings suggest that tau burden in hippocampal subfields may map closely with the distribution of SYN pathology in subfield CA2/3 in LBD diverging from traditional AD and contribute to episodic memory dysfunction in LBD.

Effects of a programme of vigorous physical activity during secondary school physical education on academic performance, fitness, cognition, mental health and the brain of adolescents (Fit to Study): study protocol for a cluster-randomised trial.

BACKGROUND: Early adolescence is a period of dynamic neurobiological change. Converging lines of research suggest that regular physical activity (PA) and improved aerobic fitness have the potential to stimulate positive brain changes, improve cognitive function and boost academic attainment in this age group, but high-quality studies are needed to substantiate these findings. The primary aim of the Fit to Study trial is to investigate whether short infusions of vigorous PA (VPA) delivered during secondary school physical education (PE) can improve attainment in maths, as described in a protocol published by NatCen Social Research. The present protocol concerns the trial's secondary outcome measures, which are variables thought to moderate or mediate the relationship between PA and attainment, including the effect of the intervention on cardiorespiratory fitness, cognitive performance, mental health and brain structure and function. METHOD: The Fit to Study project is a cluster-randomised controlled trial that includes Year 8 pupils (aged 12-13) from secondary state schools in South/Mid-England. Schools were randomised into an intervention condition in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year, or a 'PE as usual' control condition. Intervention and control groups were stratified according to whether schools were single-sex or co-educational. Assessments take place at baseline (end of Year 7, aged 11-12) and after 12 months (Year 8). Secondary outcomes are cardiorespiratory fitness, objective PA during PE, cognitive performance and mental health. The study also includes exploratory measures of daytime sleepiness, attitudes towards daily PA and PE enjoyment. A sub-set of pupils from a sub-set of schools will also take part in a brain imaging sub-study, which is embedded in the trial. DISCUSSION: The Fit to Study trial could advance our understanding of the complex relationships between PA and aerobic fitness, the brain, cognitive performance, mental health and academic attainment during adolescence. Further, it will add to our understanding of whether school PE is an effective setting to increase VPA and fitness, which could inform future PA interventions and education policy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03286725 . Retrospectively registered on 18 September 2017. ClinicalTrials.gov, NCT03593863 . Retrospectively registered on 19 July 2018.

Prediction model optimization using full model selection with regression trees demonstrated with FTIR data from bovine milk.

Predictive modeling is the development of a model that is best able to predict an outcome based on given input variables. Model algorithms are different processes that are used to define functions that transform the data within models. Common algorithms include logistic regression (LR), linear discriminant analysis (LDA), classification and regression trees (CART), naïve Bayes (NB), and k-nearest neighbor (KNN). Data preprocessing option, such as feature extraction and reduction, and model algorithms are commonly selected empirically in epidemiological studies even though these decisions can significantly affect model performance. Accordingly, full model selection (FMS) methods were developed to provide a systematic approach to select predictive modeling methods; however, current limitations of FMS, such as its dependency on user-selected hyperparameters, have prevented their routine incorporation into analyses for model performance optimization. Here we present the use of regression trees as an innovative method to apply FMS. Regression tree FMS (rtFMS) requires the development of a model for every combination of predictive modeling method options under consideration. The iterated, cross-validation performances of these models are then passed through a regression tree for selection of a final model. We demonstrate the benefits of rtFMS using a milk Fourier transform infrared spectroscopy dataset, wherein we build prediction models for two blood metabolic health parameters in dairy cows, nonesterified fatty acids (NEFA) and ß-hydroxybutyrate acid (BHBA). The goal for building NEFA and BHBA prediction models is to provide a milk-based screening tool for metabolic health in dairy cattle that can be incorporated automatically in milk analysis routines. These models could be used in conjunction with physical exams, cow side tests, and other indications to initiate medical intervention. In contrast to previously reported FMS methods, rtFMS is not a black box, is simple to implement and interpret, it does not have hyperparameters, and it illustrates the relative importance of modeling options. Additionally, rtFMS allows for indirect comparisons among models developed using different datasets. Finally, rtFMS eliminates user bias due to personal preference for certain methods and rtFMS removes the dependency on published comparisons of methods. Thus, rtFMS provides clear benefits over the empirical selection of data preprocessing options and model algorithms.

Does the intensity of daily walking matter for protecting against the development of a slow gait speed in people with or at high risk of knee osteoarthritis? An observational study.

OBJECTIVE: Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA. METHOD: We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (<1 steps/min), very-light (1-49 steps/min), light (50-100 steps/min), and moderate-to-vigorous (>100 steps/min). We defined slow gait during a 20-m walk, as <1 m/s and <1.2 m/s. Isotemporal substitution evaluated time-substitution effects on incident slow gait outcomes at 2-years. RESULTS: Replacing 20 min/day of not walking with walking at a moderate-to-vigorous intensity, demonstrated small to moderate reductions in the risk of developing a gait speed <1.0 m/s (Relative Risk [95% confidence interval (CI)]; MOST = 0.51 [0.27, 0.98], OAI = 0.21 [0.04, 0.98]), and <1.2 m/s (MOST = 0.73 [0.53, 1.00], OAI = 0.65 [0.36, 1.18]). However, only risk reductions for <1.0 m/s met statistical significance. Replacing not walking with very-light or light intensity walking was not associated with the risk of developing slow gait outcomes. CONCLUSION: When possible, walking at a moderate-to-vigorous intensity (>100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA.

Identifying poor metabolic adaptation during early lactation in dairy cows using cluster analysis.

Currently, cows with poor metabolic adaptation during early lactation, or poor metabolic adaptation syndrome (PMAS), are often identified based on detection of hyperketonemia. Unfortunately, elevated blood ketones do not manifest consistently with indications of PMAS. Expected indicators of PMAS include elevated liver enzymes and bilirubin, decreased rumen fill, reduced rumen contractions, and a decrease in milk production. Cows with PMAS typically are higher producing, older cows that are earlier in lactation and have greater body condition score at the start of lactation. It was our aim to evaluate commonly used measures of metabolic health (input variables) that were available [i.e., blood ß-hydroxybutyrate acid, milk fat:protein ratio, blood nonesterified fatty acids (NEFA)] to characterize PMAS. Bavarian farms (n = 26) with robotic milking systems were enrolled for weekly visits for an average of 6.7 wk. Physical examinations of the cows (5-50 d in milk) were performed by veterinarians during each visit, and blood and milk samples were collected. Resulting data included 790 observations from 312 cows (309 Simmental, 1 Red Holstein, 2 Holstein). Principal component analysis was conducted on the 3 input variables, followed by K-means cluster analysis of the first 2 orthogonal components. The 5 resulting clusters were then ascribed to low, intermediate, or high PMAS classes based on their degree of agreement with expected PMAS indicators and characteristics in comparison with other clusters. Results revealed that PMAS classes were most significantly associated with blood NEFA levels. Next, we evaluated NEFA values that classify observations into appropriate PMAS classes in this data set, which we called separation values. Our resulting NEFA separation values [<0.39 mmol/L (95% confidence limits = 0.360-0.410) to identify low PMAS observations and ≥0.7 mmol/L (95% confidence limits = 0.650-0.775) to identify high PMAS observations] were similar to values determined for Holsteins in conventional milking settings diagnosed with hyperketonemia and clinical symptoms such as anorexia and a reduction in milk yield, as reported in the literature. Future studies evaluating additional clinical and laboratory data, breeds, and milking systems are needed to validate these finding. The aim of future studies would be to build a PMAS prediction model to alert producers of cows needing attention and help evaluate on-farm metabolic health management at the herd level.

Tracing the fate of steroids through a hypersaline microbial mat (Kiritimati, Kiribati/Central Pacific).

Eukaryotic steranes are typically absent or occur in very low concentrations in Precambrian sedimentary rocks. However, it is as yet unclear whether this may reflect low source inputs or a preservational bias. For instance, it has been proposed that eukaryotic lipids were profoundly degraded in benthic microbial mats that were ubiquitous prior to the advent of vertical bioturbation in the Cambrian ("mat-seal effect"). It is therefore important to test the microbial turnover and degradation of eukaryotic steroids in real-world microbial mats. Here we assessed steroid inventories in different layers of a microbial mat from a hypersaline lake on Kiritimati (Central Pacific). Various eukaryote-derived C27 -C30 steroids were detected in all mat layers. These compounds most likely entered the mat system as unsaturated sterols from the water column or the topmost mat, and were progressively altered during burial in the deeper, anoxic mat layers over c. 103  years. This is reflected by increasing proportions of saturated sterols and sterenes, as well as the presence of thiosteranes in certain horizons. Sterol alteration can partly be assigned to microbial transformation but is also due to chemical reactions promoted by the reducing environment in the deeper mat layers. Notably, however, compounds with a sterane skeleton were similarly abundant in all mat layers and their absolute concentrations did not show any systematic decrease. The observed decrease of steroid/hopanoid ratios with depth may thus rather indicate a progressive "dilution" by lipids derived from heterotrophic bacteria. Further, pyrolysis revealed that steroids, in contrast to hopanoids, were not sequestered into non-extractable organic matter. This may lead to a preservational bias against steroids during later stages of burial. Taken together, steroid preservation in the microbial mat is not only controlled by heterotrophic degradation, but rather reflects a complex interplay of taphonomic processes.

The taphonomic fate of isorenieratene in Lower Jurassic shales-controlled by iron?

Fossil derivatives of isorenieratene, an accessory pigment in brown-colored green sulfur bacteria, are often used as tracers for photic zone anoxia through Earth's history, but their diagenetic behavior is still incompletely understood. Here, we assess the preservation of isorenieratene derivatives in organic-rich shales (1.5-8.4 wt.% TOC) from two Lower Jurassic anoxic systems (Bächental oil shale, Tyrol, Austria; Posidonia Shale, Baden-Württemberg, Germany). Bitumens and kerogens were investigated using catalytic hydropyrolysis (HyPy), closed-system hydrous pyrolysis (in gold capsules), gas chromatography-mass spectrometry (GC-MS) and gas chromatography combustion isotope ratio-mass spectrometry (GC-C-IRMS). Petrography and biomarkers indicate a syngenetic relationship between bitumens and kerogens. All bitumens contain abundant isorenieratane, diverse complex aromatized isorenieratene derivatives, and a pseudohomologous series of 2,3,6-trimethyl aryl isoprenoids. In contrast, HyPy and mild closed-system hydrous pyrolysis of the kerogens yielded only minor amounts of these compounds. Given the overall low maturity of the organic matter (below oil window), it appears that isorenieratene and its abundant derivatives from the bitumen had not been incorporated into the kerogens. Accordingly, sulfur cross-linking, the key mechanism for sequestration of functionalized lipids into kerogens in anoxic systems, was not effective in the Jurassic environments studied. We explain this by (i) early cyclization/aromatization and (ii) hydrogenation reactions that have prevented effective sulfurization. In addition, (iii) sulfide was locally removed via anoxygenic photosynthesis and efficiently trapped by the reaction with sedimentary iron, as further indicated by elevated iron contents (4.0-8.7 wt.%) and the presence of abundant pyrite aggregates in the rock matrix. Although the combined processes have hampered the kerogen incorporation of isorenieratene and its derivatives, they may have promoted the long-term preservation of these biomarkers in the bitumen fraction via early defunctionalization. This particular taphonomy of aromatic carotenoids has to be considered in studies of anoxic iron-rich environments (e.g., the Proterozoic ocean).

[Comparison of the Arthroscopic Finding in the Knee Joint and the MRI - Retrospective Study]. / Porovnání artroskopického nálezu kolenního kloubu s magnetickou rezonancí ­ retrospektivní studie.

PURPOSE OF THE STUDY Our retrospective study presents the comparison of the preoperative magnetic resonance imaging of the knee joint - MRI - and the arthroscopic finding - ASC. Its aim is to find out how a positive or a negative finding of MRI corresponds with the operative finding and how much the experience of radiologist contributes to the conformity. MATERIAL AND METHODS The MRI findings of knee joints treated surgically at two departments in 2013 and 2014 were assessed. The MRI was performed in a total of 470 patients who subsequently underwent an arthroscopic surgery. A conformity or a non-conformity in anterior, posterior horn and complete rupture of both menisci and in partial or complete tear of anterior cruciate ligament - LCA was searched for. The sensitivity, specificity and accuracy of MRI were established. The difference between experienced and less experienced radiologists was evaluated. The analysis of the radiology report, surgical protocol of ASC and medical history in the documentation was performed. The cartilage was not subject to evaluation. The finding of Grade 1 meniscus tear on MRI was evaluated as negative. Grade 2 and Grade 3 were evaluated as positive. RESULTS Comparison of the preoperative MRI and the arthroscopic finding 1. The group with MRI reported 3 % of diagnostic arthroscopies. The control group without MRI (551 ASC) reported 15 % diagnostic arthroscopies. 2. Low sensitivity of MRI (0.67) in negative findings of ASC. It concerned 7 cases in which a pathological finding was identified on a MRI scan, but not by ASC. In two cases the repeated arthroscopy confirmed that a pathology inside the knee joint was overlooked by the arthroscopist. In the remaining five cases, the clinical finding improved without a repeated surgery. 3. High sensitivity of MRI is shown in the most frequent finding - posterior horn of medial meniscus (0.94). 4. Lower sensitivity (0.76) in partial and (0.83) in complete ACL tear. It increases to 0.93 if partial and complete tear are put together. Both MRI and ASC detect the pathology of ligament, but do not agree in terms of terminology. 5. Lower sensitivity (0.78) was seen in posterior horn of lateral meniscus, most likely due to its complicated anatomy. 6. Specificity of complete tear of medial meniscus tear is 0.99. Lower specificity in the posterior horn of medial meniscus (0.81) shows a higher number of positive MRI findings in negative ASC findings. Some posterior horn tear can be overlooked by an inexperienced surgeon. The MRD findings need to be studied. 7. High specificity (0.99) was described in negative findings. In three cases only, the surgeon discovered a pathological finding, not revealed by MRI scan. It always concerned a tear within the posterior horn of the medial meniscus. 8. Specificity (0.88, 0.93 or 0.86, respectively) in partial, complete and all ACL damages in total. 9. We concluded that contributing to the degree of agreement between MRI and ASC is also the experience of a radiologist. The most experienced radiologist evaluated 190 of 470 MRI scans, the remaining twelve radiologists assessed 280 scans. The posterior horn of the medial meniscus - sensitivity or specificity evaluated by an experienced radiologist (0.98 and 0.88, respectively) and inexperienced radiologist (0.91 and 0.79). The specificity and sensitivity in complete ACL tears - by experienced radiologist (0.91 and 0.94, respectively) and inexperienced radiologist (0.81 and 0.90, respectively). The test accuracy of the experienced radiologist in evaluating the most frequent injuries of soft knee structures was by 9-10 % higher than of the inexperienced radiologist. DISCUSSION The results obtained by the other authors show that the sensitivity and specificity range from 0.6 to 0.9. They agree that the MRI is unsuitable for assessing the cartilage. We confirm that the results are worse when evaluating the posterior horn of the lateral meniscus. We have also proven that the radiologist s experience does play an important role. It can be the reason for a high degree of difference between the results of various authors. Some of them give preference to a clinical examination or a diagnostic arthroscopy instead of the MRI. At our department, MRI is indicated if we are convinced it can help with the indication or where it will suggest what to focus on during the surgery. CONCLUSIONS A preoperative MRI scan can prevent an unnecessary arthroscopy. It displays structures to the surgeon which shall be reviewed in detail during the surgery. We recommend paying attention to Grade 2 MRI findings, positive MRI findings on the posterior horn of medial meniscus and to MRI findings on partial ACL tears. Such menisci and ligaments shall be carefully reviewed. Clinical preoperative examination and cooperation between the surgeon, the "arthroscopist", and the radiologist is essential. The experience of the radiologist also plays a role when evaluating the MRI scan. We have introduced MRI ward rounds. Key words: MRI, knee joint, knee arthroscopy, sensitivity, specificity, accuracy.

INTERNATIONAL STANDARDS ON FOOD AND ENVIRONMENTAL RADIOACTIVITY MEASUREMENT FOR RADIOLOGICAL PROTECTION: STATUS AND PERSPECTIVES.

Radiological protection is a matter of concern for members of the public and thus national authorities are more likely to trust the quality of radioactivity data provided by accredited laboratories using common standards. Normative approach based on international standards aims to ensure the accuracy or validity of the test result through calibrations and measurements traceable to the International System of Units. This approach guarantees that radioactivity test results on the same types of samples are comparable over time and space as well as between different testing laboratories. Today, testing laboratories involved in radioactivity measurement have a set of more than 150 international standards to help them perform their work. Most of them are published by the International Standardization Organization (ISO) and the International Electrotechnical Commission (IEC). This paper reviews the most essential ISO standards that give guidance to testing laboratories at different stages from sampling planning to the transmission of the test report to their customers, summarizes recent activities and achievements and present the perspectives on new standards under development by the ISO Working Groups dealing with radioactivity measurement in connection with radiological protection.

A test of basic psychological needs theory in young soccer players: time-lagged design at the individual and team levels.

Within the framework of basic psychological needs theory (Deci & Ryan, 2000), multilevel structural equation modeling (MSEM) with a time-lagged design was used to test a mediation model examining the relationship between perceptions of coaches' interpersonal styles (autonomy supportive and controlling), athletes' basic psychological needs (satisfaction and thwarting), and indicators of well-being (subjective vitality) and ill-being (burnout), estimating separately between and within effects. The participants were 597 Spanish male soccer players aged between 11 and 14 years (M = 12.57, SD = 0.54) from 40 teams who completed a questionnaire package at two time points in a competitive season. Results revealed that at the individual level, athletes' perceptions of autonomy support positively predicted athletes' need satisfaction (autonomy, competence, and relatedness), whereas athletes' perceptions of controlling style positively predicted athletes' need thwarting (autonomy, competence, and relatedness). In turn, all three athletes' need satisfaction dimensions predicted athletes' subjective vitality and burnout (positively and negatively, respectively), whereas competence thwarting negatively predicted subjective vitality and competence and relatedness positively predicted burnout. At the team level, team perceptions of autonomy supportive style positively predicted team autonomy and relatedness satisfaction. Mediation effects only appeared at the individual level.

Influence of CYP2D6 and CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy volunteers.

PURPOSE: This is the first study that connects pharmacokinetics of tolperisone with genetic polymorphism of the enzymes involved in its metabolism in human. We aimed to identify the influence of polymorphism of two main enzymes (CYP2D6 and CYP2C19) on pharmacokinetic profile of parent drug. METHODS: In a single-dose study, 28 healthy Caucasian male volunteers received an oral dose of 150 mg of tolperisone. The subjects were genotyped with respect to CYP2D6 and CYP2C19 enzymes. Plasma was sampled for up to 12 h post dose, followed by quantification of tolperisone by a fully validated HPLC-tandem mass spectrometry (MS/MS) method. The pharmacokinetic parameters were estimated using a non-compartmental method and compared statistically at level p < 0.05 across the genotyped groups. RESULTS: High variability (exceeded 100%) of main bioavailability parameters (AUCt, AUC(inf), C(max)) was observed in the whole group of subjects. An essential difference in the pharmacokinetics of tolperisone of quick metabolizers whose genotype expressed wild homozygote CYP2D6 *1/*1 with respect to heterozygous *1/*4 and *1/*5 subjects was demonstrated. The mean AUC(inf) was 2.1- and 3.4-fold higher in *1/*4 and *1/*5, respectively, than in *1/*1 subjects. In case of Cmax, the differences were greater and reached maximally 3.8 times (mean values 54.00, 98.85, and 205.20 ng/mL for CYP2D6 *1/*1, *1/*4, and *1/*5, respectively). Values of the parameters for the one subject that expressed *4/*4 genotype were even 8.5 times higher than in subjects with extensive or intermediate phenotype. Although CYP2C19 *1/*2 subjects had higher AUCt, AUC(inf), and Cmax values than *1/*1, no statistically significant differences were observed. Oral clearance (CL/F) significantly decreased by 65.7% in heterozygous *1/*2 relative to homozygous *1/*1 extensive metabolizers. CONCLUSION: In this study, we first demonstrated the effect of CYP2D6 polymorphism on pharmacokinetics of tolperisone in Caucasian subjects. The contribution of CYP2C19 enzyme seems to be less important.

Changes in work affect in response to lunchtime walking in previously physically inactive employees: A randomized trial.

Physical activity may regulate affective experiences at work, but controlled studies are needed and there has been a reliance on retrospective accounts of experience. The purpose of the present study was to examine the effect of lunchtime walks on momentary work affect at the individual and group levels. Physically inactive employees (N = 56; M age = 47.68; 92.86% female) from a large university in the UK were randomized to immediate treatment or delayed treatment (DT). The DT participants completed both a control and intervention period. During the intervention period, participants partook in three weekly 30-min lunchtime group-led walks for 10 weeks. They completed twice daily affective reports at work (morning and afternoon) using mobile phones on two randomly chosen days per week. Multilevel modeling was used to analyze the data. Lunchtime walks improved enthusiasm, relaxation, and nervousness at work, although the pattern of results differed depending on whether between-group or within-person analyses were conducted. The intervention was effective in changing some affective states and may have broader implications for public health and workplace performance.

Molecular dynamics studies of material property effects on thermal boundary conductance.

Thermal boundary resistance (inverse of conductance) between different material layers can dominate the overall thermal resistance in nanostructures and therefore impact the performance of the thermal property limiting nano devices. Because relationships between material properties and thermal boundary conductance have not been fully understood, optimum devices cannot be developed through a rational selection of materials. Here we develop generic interatomic potentials to enable material properties to be continuously varied in extremely large molecular dynamics simulations to explore the dependence of thermal boundary conductance on the characteristic properties of materials such as atomic mass, stiffness, and interfacial crystallography. To ensure that our study is not biased to a particular model, we employ different types of interatomic potentials. In particular, both a Stillinger-Weber potential and a hybrid embedded-atom-method + Stillinger-Weber potential are used to study metal-on-semiconductor compound interfaces, and the results are analyzed considering previous work based upon a Lennard-Jones (LJ) potential. These studies, therefore, reliably provide new understanding of interfacial transport phenomena particularly in terms of effects of material properties on thermal boundary conductance. Our most important finding is that thermal boundary conductance increases with the overlap of the vibrational spectra between metal modes and the acoustic modes of the semiconductor compound, and increasing the metal stiffness causes a continuous shift of the metal modes. As a result, the maximum thermal boundary conductance occurs at an intermediate metal stiffness (best matched to the semiconductor stiffness) that maximizes the overlap of the vibrational modes.

Cardiorespiratory Fitness in Women with and without Lymphedema following Breast Cancer Treatment.

Following breast cancer (BC) treatment, many women develop impairments that may impact cardiorespiratory (CR) fitness. The aims of this study were to 1) evaluate CR fitness in women following BC treatment, 2) evaluate differences in CR fitness in those with and without breast cancer-related lymphedema (BCRL) and compare these to age-matched norms, and 3) evaluate the contribution of predictor variables to CR fitness. 136 women post-BC treatment completed testing: 67 with BCRL, and 69 without. VO2 peak was lower in participants compared to published healthy age-matched norms. VO2 peak was statistically significantly lower in women with BCRL. Age, BMI, meeting recommended exercise criteria, and DASH scores explained 50% of the variance in VO2 peak (R=0.708, p<0.001). Following BC treatment CR fitness may be impaired, more-so in women with BCRL. This should be considered when providing rehabilitation for women following BC treatment as cardiorespiratory fitness has linked to improved health outcomes and survivorship.

[Long-term outcome of catheter ablation therapy of supraventricular tachyarrhythmias]. / Dlouhodobé výsledky katetrizacní ablacní lécby u supraventrikulárních tachyarytmií.

AIM: The aim of the article is presentation of our results and experiences with radiofrequency catheter ablation (CA) in the therapy of supraventricular tachyarrhythmias. PATIENTS AND METHODS: From 1996 to 2009, 1 485 patients underwent CA (total procedure number - 1 627). The group consist of 772 patients with paroxysmal atrioventricular nodal reentry tachycardia (AVNRT): 484 women, mean age 50.3 +/- 16.4 years; 312 patients with atrioventricular reentry tachycardia (AVRT): 145 women, mean age 40.1 +/- 14.9 years; 391 patients with typical atrial flutter (AF): 96 women, mean age 61.6 +/- 11 years; and 64 patients with atrial tachycardia (AT): 35 women, mean age 53.6 +/- 14.2 years, focal AT 33, macroreentrant AT 31. CA was performed for more than one type of arrhythmia in 54 patients. RESULTS: Acute ablation success was achieved in 98.7% of patients with AVNRT, 94.6% of patients with AVRT, 97.7% of patients with AF, and 81.3% of patients with AT. Serious procedure complications occurred in 22 patients (1.4%). The recurrence rate was 1.8-12.5%. 88 patients underwent successful reablation procedure. Long-term ablation success was achieved in 89-99% of patients depending on the different type of arrhythmia. During the long-term follow-up (mean 73 +/- 38 months) died 23 patients, the most common cause of death was malignancy (9 patients). CONCLUSION: Our long-term experience and good results documented high success rate and safety of radiofrequency catheter ablation in the therapy of patients with supraventricular tachyarrhythmias.

[Improvement of quality of life after ablation of longstanding persistent versus paroxysmal atrial fibrillation: results of 2-year follow-up]. / Zlepsení kvality zivota po ablaci dlouhodobe perzistentní versus paroxysmální fibrilace síní: výsledky dvouletého sledování.

AIMS: The purpose of the study was to assess quality of life and socio-economic parameters in patients after ablation of paroxysmal versus longstanding persistent atrial fibrillation (AF). METHODS: The study included 89 patients with paroxysmal AF and 56 patients with longstanding persistent AF who underwent ablation within 1 year, and were afterwards prospectively followed up for 2 years. Quality of life was evaluated by the EQ-5D questionnaire before and every 6 months after ablation. RESULTS: Objective, respectively subjective quality of life at baseline was lower in patients with longstanding persistent AF (67 +/- 16 vs 71 +/- 10; p = 0.01, resp. 64 +/- 12 vs 67 +/- 16; p = 0.07); however, after 2 years, it exceeded that of the patients with paroxysmal AF (80 +/- 17 vs 75 +/- 18; p = 0.03; resp. 73 +/- 13 vs 70 +/- 17; p = 0.18). The baseline-2 year difference in improvement was higher in patients with longstanding persistent AF in both objective (p = 0.001) and subjective component (p = 0.05). Both groups displayed significant decrease in the days of hospitalization, and the days of working incapacity. CONCLUSION: Patients with longstanding persistent AF exhibit worse baseline quality of life than the patients with paroxysmal AF, and higher quality of life improvement after ablation.

TDP-43 pathology occurs infrequently in multiple system atrophy.

AIMS AND METHODS: The α-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. RESULTS: TDP-43 pathology was generally rare, and there were no FUS lesions. The TDP-43 lesions were located predominantly in medio-temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. CONCLUSIONS: The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP-43 or FUS pathology, but rather from widespread white matter α-synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary α-synuclein-mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP-43.