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Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.
Land cover change is a dynamic phenomenon driven by synergetic biophysical and socioeconomic effects. It involves massive transitions from natural to less natural habitats and thereby threatens ecosystems and the services they provide. To retain intact ecosystems and reduce land cover change to a minimum of natural transition processes, a dense network of protected areas has been established across Europe. However, even protected areas and in particular the zones around protected areas have been shown to undergo land cover changes. The aim of our study was to compare land cover changes in protected areas, non-protected areas, and 1 km buffer zones around protected areas and analyse their relationship to climatic and socioeconomic factors across Europe between 2000 and 2012 based on earth observation data. We investigated land cover flows describing major change processes: urbanisation, afforestation, deforestation, intensification of agriculture, extensification of agriculture, and formation of water bodies. Based on boosted regression trees, we modelled correlations between land cover flows and climatic and socioeconomic factors. The results show that land cover changes were most frequent in 1 km buffer zones around protected areas (3.0% of all buffer areas affected). Overall, land cover changes within protected areas were less frequent than outside, although they still amounted to 18,800 km2 (1.5% of all protected areas) from 2000 to 2012. In some parts of Europe, urbanisation and intensification of agriculture still accounted for up to 25% of land cover changes within protected areas. Modelling revealed meaningful relationships between land cover changes and a combination of influencing factors. Demographic factors (accessibility to cities and population density) were most important for coarse-scale patterns of land cover changes, whereas fine-scale patterns were most related to longitude (representing the general east/west economic gradient) and latitude (representing the north/south climatic gradient).
Cocoa Bean Proteins
(2019)
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The “state of the art” suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Cocoa Bean Proteins
(2019)
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The “state of the art” suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Land cover change is a dynamic phenomenon driven by synergetic biophysical and socioeconomic effects. It involves massive transitions from natural to less natural habitats and thereby threatens ecosystems and the services they provide. To retain intact ecosystems and reduce land cover change to a minimum of natural transition processes, a dense network of protected areas has been established across Europe. However, even protected areas and in particular the zones around protected areas have been shown to undergo land cover changes. The aim of our study was to compare land cover changes in protected areas, non-protected areas, and 1 km buffer zones around protected areas and analyse their relationship to climatic and socioeconomic factors across Europe between 2000 and 2012 based on earth observation data. We investigated land cover flows describing major change processes: urbanisation, afforestation, deforestation, intensification of agriculture, extensification of agriculture, and formation of water bodies. Based on boosted regression trees, we modelled correlations between land cover flows and climatic and socioeconomic factors. The results show that land cover changes were most frequent in 1 km buffer zones around protected areas (3.0% of all buffer areas affected). Overall, land cover changes within protected areas were less frequent than outside, although they still amounted to 18,800 km2 (1.5% of all protected areas) from 2000 to 2012. In some parts of Europe, urbanisation and intensification of agriculture still accounted for up to 25% of land cover changes within protected areas. Modelling revealed meaningful relationships between land cover changes and a combination of influencing factors. Demographic factors (accessibility to cities and population density) were most important for coarse-scale patterns of land cover changes, whereas fine-scale patterns were most related to longitude (representing the general east/west economic gradient) and latitude (representing the north/south climatic gradient).
Objectives: The objectives of this study were to determine the interrater reliability (IRR) of assessment of multiple systematic reviews (AMSTAR) 2 for reviews of pharmacological or psychological interventions for the treatment of major depression, to compare it to that of AMSTAR and risk of bias in systematic reviews (ROBIS), and to assess the convergent validity between the appraisal tools. Results: The median kappa values as a measure of IRR indicated a moderate agreement for AMSTAR 2 (median = 0.51), a substantial agreement for AMSTAR (median = 0.62), and a fair agreement for ROBIS (median = 0.27). Validity results showed a positive association for AMSTAR and AMSTAR 2 (r = 0.91) as well as ROBIS and AMSTAR 2 (r = 0.84). For the overall rating, AMSTAR 2 showed a high concordance with ROBIS and a lower concordance with AMSTAR. Conclusion: The IRR of AMSTAR 2 was found to be slightly lower than the IRR of AMSTAR and higher than the IRR of ROBIS. Validity measurements indicate that AMSTAR 2 is closely related to both ROBIS and AMSTAR. (C) 2019 Elsevier Inc. All rights reserved.
BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
Background There is evidence that physical exercise training (PET) conducted at the workplace is effective in improving physical fitness and thus health. However, there is no current systematic review available that provides high-level evidence regarding the effects of PET on physical fitness in the workforce. Objectives To quantify sex-, age-, and occupation type-specific effects of PET on physical fitness and to characterize dose-response relationships of PET modalities that could maximize gains in physical fitness in the working population. Data Sources A computerized systematic literature search was conducted in the databases PubMed and Cochrane Library (2000-2019) to identify articles related to PET in workers. Study Eligibility Criteria Only randomized controlled trials with a passive control group were included if they investigated the effects of PET programs in workers and tested at least one fitness measure. Study Appraisal and Synthesis Methods Weighted mean standardised mean differences (SMDwm) were calculated using random effects models. A multivariate random effects meta-regression was computed to explain the influence of key training modalities (e.g., training frequency, session duration, intensity) on the effectiveness of PET on measures of physical fitness. Further, subgroup univariate analyses were computed for each training modality. Additionally, methodological quality of the included studies was rated with the help of the Physiotherapy Evidence Database (PEDro) Scale. Results Overall, 3423 workers aged 30-56 years participated in 17 studies (19 articles) that were eligible for inclusion. Methodological quality of the included studies was moderate with a median PEDro score of 6. Our analyses revealed significant, small-sized effects of PET on cardiorespiratory fitness (CRF), muscular endurance, and muscle power (0.29 <= SMDwm <= 0.48). Medium effects were found for CRF and muscular endurance in younger workers (<= 45 years) (SMDwm = 0.71) and white-collar workers (SMDwm = 0.60), respectively. Multivariate random effects meta-regression for CRF revealed that none of the examined training modalities predicted the effects of PET on CRF (R-2 = 0). Independently computed subgroup analyses showed significant PET effects on CRF when conducted for 9-12 weeks (SMDwm = 0.31) and for 17-20 weeks (SMDwm = 0.74). Conclusions PET effects on physical fitness in healthy workers are moderated by age (CRF) and occupation type (muscular endurance). Further, independently computed subgroup analyses indicated that the training period of the PET programs may play an important role in improving CRF in workers.
Background: The pathophysiology behind the subacute but persistent hypercoagulable state after traumatic brain injury (TBI) is poorly understood but contributes to morbidity induced by venous thromboembolism. Because platelets and their microvesicles have been hypothesized to play a role in post-traumatic hypercoagulability, administration of commonly used agents may ameliorate this coagulability. We hypothesized that utilization of aspirin, ketorolac, amitriptyline, unfractionated heparin, or enoxaparin would modulate the platelet aggregation response after TBI. Methods: Concussive TBI was induced by weight drop. Mice were then randomized to receive aspirin, ketorolac, amitriptyline, heparin, enoxaparin, or saline control at 2 and 8 h after TBI. Mice were sacrificed at 6 or 24 h after injury to determine coagulability by rotational thromboelastometry (ROTEM), platelet function testing with impedance aggregometry, and microvesicle enumeration. Platelet sphingolipid metabolites were analyzed by mass spectrometry. Results: ROTEM demonstrated increased platelet contribution to maximum clot firmness at 6 h after TBI in mice that received aspirin or amitriptyline, but this did not persist at 24 h. By contrast, adenosine diphosphate- and arachidonic acid-induced platelet aggregation at 6 h was significantly lower in mice receiving ketorolac, aspirin, and amitriptyline compared with mice receiving saline at 6 h after injury and only arachidonic acid-initiated platelet aggregation was decreased by aspirin at 24 h. There were no differences in microvesicle production at either time point. Platelet sphingosine-1-phosphate levels were decreased at 6 h in the group receiving amitriptyline and increased at 24 h along with platelet ceramide levels at 24 h in the amitriptyline group. Conclusion: After TBI, amitriptyline decreased platelet aggregability and increased contribution to clot in a manner similar to aspirin. The amitriptyline effects on platelet function and sphingolipid metabolites may represent a possible role of the acid sphingomyelinase in the hypercoagulability observed after injury. In addition, inhibition of platelet reactivity may be an underappreciated benefit of low molecular weight heparins, such as enoxaparin. (C) 2019 Elsevier Inc. All rights reserved.
While the consequences of cyberbullying victimization have received some attention in the literature, to date, little is known about the multiple types of strains in adolescents’ lives, such as whether cyberbullying victimization and peer rejection increase their vulnerability to depression and anxiety. Even though some research found that adolescents with disabilities show higher risk for cyberbullying victimization, most research has focused on typically developing adolescents. Thus, the present study focused on examining the moderating effect of peer rejection in the relationships between cyberbullying victimization, depression, and anxiety among adolescents with autism spectrum disorder. There were 128 participants (89% male; ages ranging from 11–16 years old) with autism spectrum disorder in the sixth, seventh, or eighth grade at 16 middle schools in the United States. Participants completed questionnaires on cyberbullying victimization, peer rejection, depression, and anxiety. Results revealed that cyberbullying victimization was associated positively with peer rejection, anxiety, and depression among adolescents with autism spectrum disorder. Further, peer rejection was linked positively with depression and anxiety. Peer rejection moderated the positive relationship between cyberbullying victimization and depression, but not anxiety. Implications for prevention programs and future research are discussed.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
While the consequences of cyberbullying victimization have received some attention in the literature, to date, little is known about the multiple types of strains in adolescents’ lives, such as whether cyberbullying victimization and peer rejection increase their vulnerability to depression and anxiety. Even though some research found that adolescents with disabilities show higher risk for cyberbullying victimization, most research has focused on typically developing adolescents. Thus, the present study focused on examining the moderating effect of peer rejection in the relationships between cyberbullying victimization, depression, and anxiety among adolescents with autism spectrum disorder. There were 128 participants (89% male; ages ranging from 11–16 years old) with autism spectrum disorder in the sixth, seventh, or eighth grade at 16 middle schools in the United States. Participants completed questionnaires on cyberbullying victimization, peer rejection, depression, and anxiety. Results revealed that cyberbullying victimization was associated positively with peer rejection, anxiety, and depression among adolescents with autism spectrum disorder. Further, peer rejection was linked positively with depression and anxiety. Peer rejection moderated the positive relationship between cyberbullying victimization and depression, but not anxiety. Implications for prevention programs and future research are discussed.
The aim of the study was to determine pre-interventional predictors for all-cause mortality in patients after transcatheter aortic valve implantation (TAVI) with a 12-month follow-up. From 10/2013 to 07/2015, 344 patients (80.9 +/- 5.0 years, 44.5% male) with an elective TAVI were consecutively enrolled prospectively in a multicentre cohort study. Prior to the intervention, sociodemographic parameters, echocardiographic data and comorbidities were documented. All patients performed a 6-min walk test, Short Form 12 and a Frailty Index (score consisting of activities of daily living, cognition, nutrition and mobility). Peri-interventional complications were documented. Vital status was assessed over telephone 12 months after TAVI. Predictors for all-cause mortality were identified using a multivariate regression model. At discharge, 333 patients were alive (in-hospital mortality 3.2%; n = 11). During a follow-up of 381.0 +/- 41.9 days, 46 patients (13.8%) died. The non-survivors were older (82.3 +/- 5.0 vs. 80.6 +/- 5.1 years; p = 0.035), had a higher number of comorbidities (2.6 +/- 1.3 vs. 2.1 +/- 1.3; p = 0.026) and a lower left ventricular ejection fraction (51.0 +/- 13.6 vs. 54.6 +/- 10.6%; p = 0.048). Additionally, more suffered from diabetes mellitus (60.9 vs. 44.6%; p = 0.040). While the global Frailty Index had no predictive power, its individual components, particularly nutrition (OR 0.83 per 1 pt., CI 0.72-0.95; p = 0.006) and mobility (OR 5.12, CI 1.64-16.01; p = 0.005) had a prognostic impact. Likewise, diabetes mellitus (OR 2.18, CI 1.10-4.32; p = 0.026) and EuroSCORE (OR 1.21 per 5%, CI 1.07-1.36; p = 0.002) were associated with a higher risk of all-cause mortality. Besides EuroSCORE and diabetes mellitus, nutrition status and mobility of patients scheduled for TAVI offer prognostic information for 1-year all-cause mortality and should be advocated in the creation of contemporary TAVI risk scores.
Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy. Structural changes were characterized by a heterogeneous pattern of focal microvascular rarefaction with loss of coherent microvascular networks resulting in large avascular areas. Corresponding microvascular dysfunction was evident by significantly diminished blood flow velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the cremaster muscle paralleled rarefaction in the myocardium, which was accompanied by a decrease in transcription levels not only of the transcriptional regulator HIF-1 alpha, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia in mice associates with systemic microvascular disease with rarefaction, tissue hypoxia and dysfunctional angiogenesis.
Impact of self-assessment of return to work on employable discharge from multi-component cardiac rehabilitation. Retrospective unicentric analysis of routine data from cardiac rehabilitation in patients below 65 years of age. Presentation in the "Cardiovascular rehabilitation revisited" high impact abstract session during ESC Congress 2018.
In der Humanmedizin stellt die sogenannte evidenzbasierte Medizin nach Einführung des Begriffs durch D.L. Sackett (Sackett et al. 1996) und der Gründung des Cochrane Instituts (1972) einen wichtigen Standard in der Aufbereitung und dem Transfer von Ergebnissen aus klinischen Studien in den ärztlichen Alltag dar. Ziel ist es, die Vermittlung von Erkenntnissen aus der Wissenschaft für die praktizierenden Ärzte zu erleichtern. Dabei werden Studienergebnisse in Abhängigkeit von der jeweiligen Fragestellung mittels systematischer Literaturrecherche zusammengetragen und hinsichtlich ihrer Evidenz bewertet, um so dem Arzt ein Instrument an die Hand zu geben, mit dem die gewonnenen Erkenntnisse im Hinblick auf eine konkrete klinische Situation abgewogen und angewendet werden können. In den letzten Jahren wurde allerdings vermehrt Kritik laut, dass der Ausgang vieler klinischer Studien in den Übersichtsarbeiten zu positiv dargestellt werde. Ursächlich hierfür ist der Aspekt des Publikationsbias, also die Beobachtung, dass Autoren wissenschaftliche Ergebnisse mit positivem Ausgang bevorzugt publizieren. Überträgt man diesen Sachverhalt auf die präklinische Forschung, die in weiten Teilen auf der Durchführung tierexperimenteller Untersuchungen beruht, so widerspräche das Zurückhalten negativer Ergebnisse in fataler Weise dem 3R-Konzept von Russel und Burch, da dadurch die Gefahr besteht, dass Forschungsvorhaben wiederholt durchgeführt werden.
Background: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. Results: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r= 0.26, p < 0.01) levels, as well as HOMA-IR values (r= 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95% Cl =1.42 -9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95% Cl = 1.30-9.20, p = 0.01) and 3.6 (95% CI = 1.33- 9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r 0.18, p < 0.05), but not found this relationship in RBP4. Conclusions: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.
Multi-element determination in human samples is very challenging. Especially in human intervention studies sample volumes are often limited to a few microliters and due to the high number of samples a high-throughput is indispensable. Here, we present a state-of-the-art ICP-MS/MS-based method for the analysis of essential (trace) elements, namely Mg, Ca, Fe, Cu, Zn, Mo, Se and I, as well as food-relevant toxic elements such as As and Cd. The developed method was validated regarding linearity of the calibration curves, method LODs and LOQs, selectivity and trueness as well as precision. The established reliable method was applied to quantify the element serum concentrations of participants of a human intervention study (LeguAN). The participants received isocaloric diets, either rich in plant protein or in animal protein. While the serum concentrations of Mg and Mo increased in participants receiving the plant protein-based diet (above all legumes), the Se concentration in serum decreased. In contrast, the animal protein-based diet, rich in meat and dairy products, resulted in an increased Se concentration in serum.
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
Objectives: The use of simulated and standardized patients (SP) is widely accepted in the medical field and, from there, is beginning to disseminate into clinical psychology and psychotherapy. The purpose of this study was therefore to systematically review barriers and facilitators that should be considered in the implementation of SP interventions specific to clinical psychology and psychotherapy. Methods: Following current guidelines, a scoping review was conducted. The literature search focused on the MEDLINE,PsycINFO and Web of Science databases, including Dissertation Abstracts International. After screening for titles and abstracts,full texts were screened independently and in duplicate according to our inclusion criteria. For data extraction, a pre-defined form was piloted and used. Units of meaning with respect to barriers and facilitators were extracted and categorized inductively using content-analysis techniques. From the results, a matrix of interconnections and a network graph were compiled. Results: The 41 included publications were mainly in the fields of psychiatry and mental health nursing, as well as in training and education. The detailed category system contrasts four supercategories, i.e., which organizational and economic aspects to consider, which persons to include as eligible SPs, how to develop adequate scenarios, and how to authentically and consistently portray mental health patients.Conclusions: Publications focused especially on the interrelation between authenticity and consistency of portrayals, on how to evoke empathy in learners, and on economic and training aspects. A variety of recommendations for implementing SP programs,from planning to training, monitoring, and debriefing, is provided, for example, ethical screening of and ongoing support for SPs.
Ramirez-Campillo, R, Alvarez, C, García-Pinillos, F, Sanchez-Sanchez, J, Yanci, J, Castillo, D, Loturco, I, Chaabene, H, Moran, J, and Izquierdo, M. Optimal reactive strength index: is it an accurate variable to optimize plyometric training effects on measures of physical fitness in young soccer players? J Strength Cond Res 32(4): 885–893, 2018—This study aimed to compare the effects of drop-jump training using a fixed drop-box height (i.e., 30-cm [FIXED]) vs. an optimal (OPT) drop-box height (i.e., 10-cm to 40-cm: generating an OPT reactive strength index [RSI]) in youth soccer players' physical fitness. Athletes were randomly allocated to a control group (n = 24; age = 13.7 years), a fixed drop-box height group (FIXED, n = 25; age = 13.9 years), or an OPT drop-box height group (OPT, n = 24; age = 13.1 years). Before and after 7 weeks of training, tests for the assessment of jumping (countermovement jump [CMJ], 5 multiple bounds), speed (20-m sprint time), change of direction ability (CODA [Illinois test]), strength {RSI and 5 maximal squat repetition test (5 repetition maximum [RM])}, endurance (2.4-km time trial), and kicking ability (maximal kicking distance) were undertaken. Analyses revealed main effects of time for all dependent variables (p < 0.001, d = 0.24–0.72), except for 20-m sprint time. Analyses also revealed group × time interactions for CMJ (p < 0.001, d = 0.51), depth jump (DJ) (p < 0.001, d = 0.30), 20-m sprint time (p < 0.001, d = 0.25), CODA (p < 0.001, d = 0.22), and 5RM (p < 0.01, d = 0.16). Post hoc analyses revealed increases for the FIXED group (CMJ: 7.4%, d = 0.36; DJ: 19.2%, d = 0.49; CODA: −3.1%, d = −0.21; 5RM: 10.5%, d = 0.32) and the OPT group (CMJ: 16.7%, d = 0.76; DJ: 36.1%, d = 0.79; CODA: −4.4%, d = −0.34; 5RM: 18.1%, d = 0.47). Post hoc analyses also revealed increases for the OPT group in 20-m sprint time (−3.7%, d = 0.27). Therefore, to maximize the effects of plyometric training, an OPT approach is recommended. However, using adequate fixed drop-box heights may provide a rational and practical alternative.
Grabow, L, Young, JD, Alcock, LR, Quigley, PJ, Byrne, JM, Granacher, U, Škarabot, J, and Behm, DG. Higher quadriceps roller massage forces do not amplify range-of-motion increases nor impair strength and jump performance. J Strength Cond Res 32(11): 3059–3069, 2018—Roller massage (RM) has been reported to increase range of motion (ROM) without subsequent performance decrements. However, the effects of different rolling forces have not been examined. The purpose of this study was to compare the effects of sham (RMsham), moderate (RMmod), and high (RMhigh) RM forces, calculated relative to the individuals' pain perception, on ROM, strength, and jump parameters. Sixteen healthy individuals (27 ± 4 years) participated in this study. The intervention involved three 60-second quadriceps RM bouts with RMlow (3.9/10 ± 0.64 rating of perceived pain [RPP]), RMmod (6.2/10 ± 0.64 RPP), and RMhigh (8.2/10 ± 0.44 RPP) pain conditions, respectively. A within-subject design was used to assess dependent variables (active and passive knee flexion ROM, single-leg drop jump [DJ] height, DJ contact time, DJ performance index, maximum voluntary isometric contraction [MVIC] force, and force produced in the first 200 milliseconds [F200] of the knee extensors and flexors). A 2-way repeated measures analysis of variance showed a main effect of testing time in active (p < 0.001, d = 2.54) and passive (p < 0.001, d = 3.22) ROM. Independent of the RM forces, active and passive ROM increased by 7.0% (p = 0.03, d = 2.25) and 15.4% (p < 0.001, d = 3.73) from premeasure to postmeasure, respectively. Drop jump and MVIC parameters were unaffected from pretest to posttest (p > 0.05, d = 0.33–0.84). Roller massage can be efficiently used to increase ROM without substantial pain and without subsequent performance impairments.
Background
Jump training (JT) can be used to enhance the ability of skeletal muscle to exert maximal force in as short a time as possible. Despite its usefulness as a method of performance enhancement in athletes, only a small number of studies have investigated its effects on muscle power in older adults.
Objectives
The aims of this meta-analysis were to measure the effect of JT on muscular power in older adults (≥ 50 years), and to establish appropriate programming guidelines for this population.
Data Sources
The data sources utilised were Google Scholar, PubMed, and Microsoft Academic.
Study Eligibility Criteria
Studies were eligible for inclusion if they comprised JT interventions in healthy adults (≥ 50 years) who were free of any medical condition that could impair movement.
Study Appraisal and Synthesis Methods
The inverse variance random-effects model for meta-analyses was used because it allocates a proportionate weight to trials based on the size of their individual standard errors and facilitates analysis while accounting for heterogeneity across studies. Effect sizes (ESs), calculated from a measure of muscular power, were represented by the standardised mean difference and were presented alongside 95% confidence intervals (CIs).
Results
Thirteen training groups across nine studies were included in this meta-analysis. The magnitude of the main effect was ‘moderate’ (0.66, 95% CI 0.33, 0.98). ESs were larger in non-obese participants (body mass index [BMI] < 30 vs. ≥ 30 kg/m2; 1.03 [95% CI 0.34, 1.73] vs. 0.53 [95% CI − 0.03, 1.09]). Among the studies included in this review, just one reported an acute injury, which did not result in the participant ceasing their involvement. JT was more effective in programmes with more than one exercise (range 1–4 exercises; ES = 0.74 [95% CI − 0.49, 1.96] vs. 0.53 [95% CI 0.29, 0.78]), more than two sets per exercise (range 1–4 sets; ES = 0.91 [95% CI 0.04, 1.77] vs. 0.68 [95% CI 0.15, 1.21]), more than three jumps per set (range 1–14 jumps; ES = 1.02 [95% CI 0.16, 1.87] vs. 0.53 [95% CI − 0.03, 1.09]) and more than 25 jumps per session (range 6–200 jumps; ES = 0.88 [95% CI 0.05, 1.70] vs. 0.49 [95% CI 0.14, 0.83]).
Conclusions
JT is safe and effective in older adults. Practitioners should construct varied JT programmes that include more than one exercise and comprise more than two sets per exercise, more than three jumps per set, and 60 s of recovery between sets. An upper limit of three sets per exercise and ten jumps per set is recommended. Up to three training sessions per week can be performed.
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
Objectives: Severe pneumonia may evoke acute lung injury, and sphingosine-1-phosphate is involved in the regulation of vascular permeability and immune responses. However, the role of sphingosine-1-phosphate and the sphingosine-1-phosphate producing sphingosine kinase 1 in pneumonia remains elusive. We examined the role of the sphingosine-1-phosphate system in regulating pulmonary vascular barrier function in bacterial pneumonia. Design: Controlled, in vitro, ex vivo, and in vivo laboratory study. Subjects: Female wild-type and SphK1-deficient mice, 8-10 weeks old. Human postmortem lung tissue, human blood-derived macrophages, and pulmonary microvascular endothelial cells. Interventions: Wild-type and SphK1-deficient mice were infected with Streptococcus pneumoniae. Pulmonary sphingosine-1-phosphate levels, messenger RNA expression, and permeability as well as lung morphology were analyzed. Human blood-derived macrophages and human pulmonary microvascular endothelial cells were infected with S. pneumoniae. Transcellular electrical resistance of human pulmonary microvascular endothelial cell monolayers was examined. Further, permeability of murine isolated perfused lungs was determined following exposition to sphingosine-1-phosphate and pneumolysin. Measurements and Main Results: Following S. pneumoniae infection, murine pulmonary sphingosine-1-phosphate levels and sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 expression were increased. Pneumonia-induced lung hyperpermeability was reduced in SphK1(-/-) mice compared with wild-type mice. Expression of sphingosine kinase 1 in macrophages recruited to inflamed lung areas in pneumonia was observed in murine and human lungs. S. pneumoniae induced the sphingosine kinase 1/sphingosine-1-phosphate system in blood-derived macrophages and enhanced sphingosine-1-phosphate receptor 2 expression in human pulmonary microvascular endothelial cell in vitro. In isolated mouse lungs, pneumolysin-induced hyperpermeability was dose dependently and synergistically increased by sphingosine-1-phosphate. This sphingosine-1-phosphate-induced increase was reduced by inhibition of sphingosine-1-phosphate receptor 2 or its downstream effector Rho-kinase. Conclusions: Our data suggest that targeting the sphingosine kinase 1-/sphingosine-1-phosphate-/sphingosine-1-phosphate receptor 2-signaling pathway in the lung may provide a novel therapeutic perspective in pneumococcal pneumonia for prevention of acute lung injury.
Background The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography. Methods Urine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charite Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE. Results In total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean +/- SD was predictive for the need of dialysis (no dialysis: 89.77 +/- 92.85 mu M/mM, n = 277; need for dialysis: 140.3 +/- 82.90 mu M/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60 +/- 92.50 mu M/mM, n = 280; death during follow-up: 169.88 +/- 81.52 mu M/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02 +/- 93.17 mu M/mM, n = 271; MARE: 146.64 +/- 74.68 mu M/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 pM/mM in patients who developed MARE, required dialysis or died. Conclusions Urinary cGMP/creatinine ratio >= 120 mu M/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.
Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance.
The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.
AIM To analyze neuromuscular activity patterns of the trunk in healthy controls (H) and back pain patients (BPP) during one-handed lifting of light to heavy loads. METHODS RESULTS Seven subjects (3m/4f; 32 +/- 7 years; 171 +/- 7 cm; 65 +/- 11 kg) were assigned to BPP (pain grade >= 2) and 36 (13m/23f; 28 +/- 8 years; 174 +/- 10 cm; 71 +/- 12 kg) to H (pain grade <= 1). H and BPP did not differ significantly in anthropometrics (P > 0.05). All subjects were able to lift the light and middle loads, but 57% of BPP and 22% of H were not able to lift the heavy load (all women) chi(2) analysis revealed statistically significant differences in task failure between H vs BPP (P = 0.03). EMG-RMS ranged from 33% +/- 10%/30% +/- 9% (DL, 1 kg) to 356% +/- 148%/283% +/- 80% (VR, 20 kg) in H/BPP with no statistical difference between groups regardless of load (P > 0.05). However, the EMG-RMS of the VR was greatest in all lifting tasks for both groups and increased with heavier loads. CONCLUSION Heavier loading leads to an increase (2-to 3-fold) in trunk muscle activity with comparable patterns. Heavy loading (20 kg) leads to task failure, especially in women with back pain.
Quality of mathematics education has gained significant attention in educational politics and among educators as mathematics advances the foundations of analytical thinking necessary to excel in today’s knowledge-based economy. Recent research on instructional quality has focused on students’ development of competencies. Competency-based instruction is believed to be an effective approach to instruction as it is closely aligned to educational standards. We use data from the National Assessment Study 2012 in Germany and apply the theory of planned behavior to determine what motivates mathematics teachers (n = 1660) to take a competency-based approach to instruction. Results indicate that competencies outlined in the educational standards are a tangible element of current mathematics instruction. Within the framework of this study, we identified teachers’ perceived behavior control as the strongest determinant of taking a competency-based approach to instruction. We conclude that advancement of competency-based instruction depends on teachers’ beliefs about their professional resources.
Die Lifespan-Forschung untersucht die Entwicklung von Individuen über den gesamten Lebenslauf. Die medizinische Rehabilitation hat nach geltendem Sozialrecht die Aufgabe, chronische Krankheiten abzuwenden, zu beseitigen, zu mindern, auszugleichen, eine Verschlimmerung zu verhüten und Negativfolgen für die Lebensführung zu reduzieren. Dies erfordert in wissenschaftlicher wie in praxisbezogener Hinsicht die Entwicklung einer Lebensspannenperspektive als Voraussetzung für die Klassifikation und Diagnostik chronischer Erkrankungen, die Beschreibung von verlaufsbeeinflussenden Faktoren, kritischen Lebensphasen und Critical Incidents (kritische Verlaufszeitpunkte), die Durchführung von prophylaktischen Maßnahmen, die Entwicklung von Assessmentverfahren zur Erfassung und Bewertung von Verläufen oder Vorbehandlungen, die Auswahl und Priorisierung von Interventionen, eine Behandlungs- und Behandlerkoordination auf der Zeitachse, die Präzisierung der Aufgabenstellung für spezialisierte Rehabilitationsmaßnahmen, wie beispielsweise Rehabilitationskliniken, und als Grundlage für die Sozialmedizin. Aufgrund der Vielfalt der individuellen Risikokonstellationen, Krankheitsverläufe und Behandlungssituationen über die Lebensspanne hinweg, bedarf es in der medizinischen Rehabilitation in besonderer Weise einer personalisierten Medizin, die zugleich rehabilitationsförderliche und -behindernde Umweltfaktoren im Rehabilitationsverlauf berücksichtigt.
The purpose of the present study was to examine the effects of unilateral fatigue of the knee extensors at different movement velocities on neuromuscular performance in the fatigued and non-fatigued leg. Unilateral fatigue of the knee extensors was induced in 11 healthy young men (23.7 +/- 3.8 years) at slower (60A degrees/s; FAT60) and faster movement velocities (240A degrees/s; FAT240) using an isokinetic dynamometer. A resting control (CON) condition was included. The fatigue protocols consisted of five sets of 15 maximal concentric knee extensions using the dominant leg. Before and after fatigue, peak isokinetic torque (PIT) and time to PIT (TTP) of the knee extensors as well as electromyographic (EMG) activity of vastus medialis, vastus lateralis, and biceps femoris muscles were assessed at 60 and 240A degrees/s movement velocities in the fatigued and non-fatigued leg. In the fatigued leg, significantly greater PIT decrements were observed following FAT60 and FAT240 (11-19%) compared to CON (3-4%, p = .002, d = 2.3). Further, EMG activity increased in vastus lateralis and biceps femoris muscle following FAT240 only (8-28%, 0.018 <= p <=.024, d = 1.8). In the non-fatigued leg, shorter TTP values were found after the FAT60 protocol (11-15%, p = .023, d = 2.4). No significant changes were found for EMG data in the non-fatigued leg. The present study revealed that both slower and faster velocity fatiguing contractions failed to show any evidence of cross-over fatigue on PIT. However, unilateral knee extensor fatigue protocols conducted at slower movement velocities (i.e., 60A degrees/s) appear to modulate torque production on the non-fatigued side (evident in shorter TTP values).
The integration of balance and plyometric training has been shown to provide significant improvements in sprint, jump, agility, and other performance measures in young athletes. It is not known if a specific within session balance and plyometric exercise sequence provides more effective training adaptations. The objective of the present study was to investigate the effects of using a sequence of alternating pairs of exercises versus a block (series) of all balance exercises followed by a block of plyometric exercises on components of physical fitness such as muscle strength, power, speed, agility, and balance. Twenty-six male adolescent soccer players ( 13.9 +/- 0.3 years) participated in an 8-week training program that either alternated individual balance (e. g., exercises on unstable surfaces) and plyometric (e. g., jumps, hops, rebounds) exercises or performed a block of balance exercises prior to a block of plyometric exercises within each training session. Pre- and post-training measures included proxies of strength, power, agility, sprint, and balance such as countermovement jumps, isometric back and knee extension strength, standing long jump, 10 and 30-m sprints, agility, standing stork, and Y-balance tests. Both groups exhibited significant, generally large magnitude (effect sizes) training improvements for all measures with mean performance increases of approximately > 30%. There were no significant differences between the training groups over time. The results demonstrate the effectiveness of combining balance and plyometric exercises within a training session on components of physical fitness with young adolescents. The improved performance outcomes were not significantly influenced by the within session exercise sequence.
Global effects of income and income inequality on adult height and sexual dimorphism in height
(2017)
Objectives: Average adult height of a population is considered a biomarker of the quality of the health environment and economic conditions. The causal relationships between height and income inequality are not well understood. We analyze data from 169 countries for national average heights of men and women and national-level economic factors to test two hypotheses: (1) income inequality has a greater association with average adult height than does absolute income; and (2) neither income nor income inequality has an effect on sexual dimorphism in height. Methods: Average height data come from the NCD-RisC health risk factor collaboration. Economic indicators are derived from the World Bank data archive and include gross domestic product (GDP), Gross National Income per capita adjusted for personal purchasing power (GNI_ PPP), and income equality assessed by the Gini coefficient calculated by the Wagstaff method. Results: Hypothesis 1 is supported. Greater income equality is most predictive of average height for both sexes. GNI_ PPP explains a significant, but smaller, amount of the variation. National GDP has no association with height. Hypothesis 2 is rejected. With greater average adult height there is greater sexual dimorphism. Conclusions: Findings support a growing literature on the pernicious effects of inequality on growth in height and, by extension, on health. Gradients in height reflect gradients in social disadvantage. Inequality should be considered a pollutant that disempowers people from the resources needed for their own healthy growth and development and for the health and good growth of their children.
Background: Habitual walking speed predicts many clinical conditions later in life, but it declines with age. However, which particular exercise intervention can minimize the age-related gait speed loss is unclear.
Purpose: Our objective was to determine the effects of strength, power, coordination, and multimodal exercise training on healthy old adults' habitual and fast gait speed.
Methods: We performed a computerized systematic literature search in PubMed and Web of Knowledge from January 1984 up to December 2014. Search terms included 'Resistance training', 'power training', 'coordination training', 'multimodal training', and 'gait speed (outcome term). Inclusion criteria were articles available in full text, publication period over past 30 years, human species, journal articles, clinical trials, randomized controlled trials, English as publication language, and subject age C65 years. The methodological quality of all eligible intervention studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. We computed weighted average standardized mean differences of the intervention-induced adaptations in gait speed using a random-effects model and tested for overall and individual intervention effects relative to no-exercise controls.
Results: A total of 42 studies (mean PEDro score of 5.0 +/- 1.2) were included in the analyses (2495 healthy old adults; age 74.2 years [64.4-82.7]; body mass 69.9 +/- 4.9 kg, height 1.64 +/- 0.05 m, body mass index 26.4 +/- 1.9 kg/m(2), and gait speed 1.22 +/- 0.18 m/s). The search identified only one power training study, therefore the subsequent analyses focused only on the effects of resistance, coordination, and multimodal training on gait speed. The three types of intervention improved gait speed in the three experimental groups combined (n = 1297) by 0.10 m/s (+/- 0.12) or 8.4 % (+/- 9.7), with a large effect size (ES) of 0.84. Resistance (24 studies; n = 613; 0.11 m/s; 9.3 %; ES: 0.84), coordination (eight studies, n = 198; 0.09 m/s; 7.6 %; ES: 0.76), and multimodal training (19 studies; n = 486; 0.09 m/s; 8.4 %, ES: 0.86) increased gait speed statistically and similarly.
Conclusions: Commonly used exercise interventions can functionally and clinically increase habitual and fast gait speed and help slow the loss of gait speed or delay its onset.
Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose < 6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >= 7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.