Revised contraindications for the use of non-medical WB-electromyostimulation. Evidence-based German consensus recommendations.

Whole-body electromyostimulation has proven to be a highly effective alternative to conventional resistance-type exercise training. However, due to adverse effects in the past, very extensive contraindications have been put in place for the commercial, non-medical WB-EMS market. Considering recent positive innovations e.g., federal regulation, mandatory trainer education, revised guidelines, and new scientific studies on WB-EMS application, we believe that a careful revision of the very restrictive contraindications on WB-EMS is needed. This applies all the more because many cohorts with limited options for conventional exercise have so far been excluded. During a first meeting of an evidence-based consensus process, stakeholders from various backgrounds (e.g., research, education, application) set the priorities for revising the contraindications. We decided to focus on four categories of absolute contraindications: "Arteriosclerosis, arterial circulation disorders", "Diabetes mellitus" (DM), "Tumor and cancer" (TC), "Neurologic diseases, neuronal disorders, epilepsy". Based on scientific studies, quality criteria, safety aspects and benefit/risk assessment of the category, DM and TC were moved to the relative contraindication catalogue, while arteriosclerosis/arterial circulation disorders and neurologic diseases/neuronal disorders/epilepsy were still considered as absolute contraindications. While missing evidence suggests maintaining the status of neurologic diseases/neuronal disorders as an absolute contraindication, the risk/benefit-ratio does not support the application of WB-EMS in people with arteriosclerosis/arterial circulation diseases. Despite these very cautious modifications, countries with less restrictive structures for non-medical WB-EMS should consider our approach critically before implementing the present revisions. Considering further the largely increased amount of WB-EMS trials we advice regular updates of the present contraindication list.

Fatigue as a key factor for testing knee stability with single leg drop landing for injury prevention and return to play tests.

Objectives: Fatigue can decrease knee stability and increase the injury risk. However, fatigue is rarely being applied throughout movement analysis. The aim of this study was to investigate if the knee stability throughout SLDLs differ between cyclic and acyclic sports, before and after fatigue in general, and between the dominant and non-dominant leg of soccer players. Methods: A total of 43 active male (n = 34) and female (n = 9) athletes (age: 26.5 ± 7.2) participated in this study with a pre-post-design. Subjects performed a single leg drop landing (SLDL) from a plyobox. For each leg, the two-dimensional frontal plane projection angle (FPPA) was analyzed. After pretesting the shuttle run test was performed until exhaustion, before repeating the measurements. Results: ANOVA with repeated measures was applied and identified no significance difference for the FPPA between cyclic and acyclic sports (F = 0.98, p = 0.33), a significant difference before and after fatigue (F = 12.49, p = 0.002) and no significant difference between the dominant and non dominant leg of soccer players (F = 4.35, p = 0.26). Discussion: Fatigue seems to be able to have a significant influence on knee stability in the frontal axis. Therefore, fatigue should be included in motion analysis for injury prevention and return to play tests because during this physical state most injuries happen.

Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy.

Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8+ T cells are excluded. Engineering CD8+ T cells with chemokine receptors is a potent strategy to turn this mechanism of directed immune cell recruitment against the tumor. Here, we utilized fluorescent tagging to track the migratory behavior of tumor-specific T cells engineered with a library of all murine chemokine receptors in vivo. We then asked whether chemokine receptor-mediated redirection of antigen-specific T cells into tumors or tumor-draining lymph nodes showed superior anti-tumoral activity. We found that both targeting approaches showed higher therapeutic efficacy than control T cells. However, multiple receptors conveying the same homing pattern did not augment infiltration. Instead, in the MC38 colon carcinoma model, anti-tumoral efficacy as well as lymph node vs. tumor-homing patterns were mostly driven by CCR4 and CCR6, respectively. Overall, our data, based on fluorescent receptor tagging, identify the tumor-draining lymph node and the tumor itself as viable targets for chemokine receptor-mediated enhancement of adoptive T cell therapy.

Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection.

Upon viral infection, natural killer (NK) cells expressing certain germline-encoded receptors are selected, expanded, and maintained in an adaptive-like manner. Currently, these are thought to differentiate along a common pathway. However, by fate mapping of single NK cells upon murine cytomegalovirus (MCMV) infection, we identified two distinct NK cell lineages that contributed to adaptive-like responses. One was equivalent to conventional NK (cNK) cells while the other was transcriptionally similar to type 1 innate lymphoid cells (ILC1s). ILC1-like NK cells showed splenic residency and strong cytokine production but also recognized and killed MCMV-infected cells, guided by activating receptor Ly49H. Moreover, they induced clustering of conventional type 1 dendritic cells and facilitated antigen-specific T cell priming early during MCMV infection, which depended on Ly49H and the NK cell-intrinsic expression of transcription factor Batf3. Thereby, ILC1-like NK cells bridge innate and adaptive viral recognition and unite critical features of cNK cells and ILC1s.

Early emergence of T central memory precursors programs clonal dominance during chronic viral infection.

Chronic cytomegalovirus (CMV) infection leads to long-term maintenance of extraordinarily large CMV-specific T cell populations. The magnitude of this so-called 'memory inflation' is thought to mainly depend on antigenic stimulation during the chronic phase of infection. However, by mapping the long-term development of CD8+ T cell families derived from single naive precursors, we find that fate decisions made during the acute phase of murine CMV infection can alter the level of memory inflation by more than 1,000-fold. Counterintuitively, a T cell family's capacity for memory inflation is not determined by its initial expansion. Instead, those rare T cell families that dominate the chronic phase of infection show an early transcriptomic signature akin to that of established T central memory cells. Accordingly, a T cell family's long-term dominance is best predicted by its early content of T central memory precursors, which later serve as a stem-cell-like source for memory inflation.

Distinct Surface Expression of Activating Receptor Ly49H Drives Differential Expansion of NK Cell Clones upon Murine Cytomegalovirus Infection.

Natural killer (NK) cells show some features of adaptive immunity but have not been studied at the clonal level. Here, we used retrogenic color-barcoding and single-cell adoptive transfers to track clonal immune responses to murine cytomegalovirus (MCMV) infection, derived from individual NK cells expressing activating receptor Ly49H. Clonal expansion of single NK cells varied substantially, and this variation could not be attributed to the additional presence or absence of inhibitory Ly49 receptors. Instead, single-cell-derived variability correlated with distinct surface expression levels of Ly49H itself. Ly49Hhi NK cell clones maintained higher Ly49H expression and expanded more than their Ly49Hlo counterparts in response to MCMV. Thus, akin to adaptive processes shaping an antigen-specific T cell receptor (TCR) repertoire, the Ly49H+ NK cell population adapts to MCMV infection. This process relies on the clonal maintenance of distinct Ly49H expression levels, generating a repertoire of individual NK cells outfitted with distinct reactivity to MCMV.

Groin Pain and Muscular Imbalance of Quadriceps and Hamstrings in an Elite Soccer Player - A Case Study.

Soccer and football players are exposed to a high risk of groin pain. In some cases, the pubic symphysis is the origin of the problems.This article presents a case report of a young elite soccer player who, over a period of two years, suffered from pain in the groin and symphysis area. The right leg was the kicking leg. Imaging techniques did not reveal pathological findings. Sports hernia, osteomyelitis, enthesopathy, adductor tendonitis, and muscle sprains, as well as rheumatic or urogenital disorders were excluded.A 3 D posture analysis was performed to examine the statics of the body and pelvis. The maximum isometric strength of the left and right leg adductors and abductors, as well as the knee flexors and extensors were measured.We found a muscular imbalance resulting from the type of sport the athlete engaged in with an unfavourable ratio between the right knee extensor and flexor muscles. Comparing sides, an imbalance was also identified between the right and left knee extensor. This imbalance resulted in a one-sided forward tilt of the right hemi-pelvis. This pelvic torsion may lead to an increase in shear forces in the pubic symphysis, which we suspected to be the reason for the recurring problems.After three months of specific training exercises, the pelvic position was harmonised and the muscular imbalances were significantly reduced. Even 6 months after completion of the specific training exercises, the player remained without complaints despite his unvaried soccer training intensity.Causal treatment of functional pain in the groin or symphysis area should take into account the ipsilateral and contralateral strength ratios of the knee extensors and flexors as well as the three-dimensional position of the pelvis.

[Injury of the Obturator Internus Muscle--a Rare Differential Diagnosis in a Soccer Player]. / Verletzung des M. obturatorius internus--eine seltene Differenzialdiagnose beim Fußballspieler.

BACKGROUND: Lesions/irritations of the obturator internus muscle (OIM) are rare, several differential diagnoses are possible. PATIENT: This paper describes the case of an OIM injury in a professional football player. RESULTS: On clinical examination, painful internal rotation of the hip joint was an indication for a lesion/irritation of the OIM. MRI was the procedure of choice for imaging. Movement analysis served to detect a functional malposition. CONCLUSION: A short recovery time requires functional treatment as well as the use of orthopaedic aids to correct possible deformities.

Empirical evidence of the efficiency and efficacy of fat taxes and thin subsidies.

This study summarizes the empirical literature on fat taxes and thin subsidies to assess their efficiency and efficacy as instruments of public policy to control obesity. Three specific types of taxes are studied in the literature: food group taxes; nutrient taxes; and nutrient index taxes. Anumber of studies use food expenditure data to assess the impact of various taxes on obesity and therefore only indirectly measure the impacts of taxes and subsidies on obesity. These studies generally conclude that food group taxes, nutrient taxes and nutrient index taxes have a small impact on the purchases of food and the nutrients purchased. Other studies use the body mass index as the explanatory variable and thus measure the impacts of taxes on body mass index directly. Nutrient taxes are found to be more effective than food group taxes, although even for nutrient taxes, the effects are small. In general, thin subsidies seem to offer more effective control of obesity than obesity taxes. However, due to the small effects of both fat taxes and thin subsidies, they are not recommended as instruments of food and nutrition policy.

[Acute and overuse injuries in soccer - what about the evidence level?]. / Verletzungen und Schäden im Fußball - Wie hoch ist die Evidenz?

AIM: Over the last years, several studies on harmful events (h. e.) in soccer have been published. The aim was to develop a ranking of these studies according to their evidence, and to analyse the data with respect to the number of study participants, athletes' status, gender distribution, and genesis of harmful events in soccer. METHODS: Between 1976 and 2011, the data bases MEDLINE, EBMR, and SPOTLIT were scanned by the keywords/combinations: soccer, acute injuries, overuse injuries, training, and match. In doing so, 644 initially potential relevant articles were found. On the basis of the QUORUM standard, 78 potentially relevant articles were filtered out, and an EVIDENCE BASED LEVEL (EBL) was assigned. The results were rated according to importance and shown descriptively, because the heterogeneity of the study inhibited meta-analytical evaluation. RESULTS: 23 % of the publications could be assigned to EBL 2a - 2c, 27 % to EBL 3a and 3b, and 50 % to EBL 4 and 5. The studies comprised altogether 22 294 male and 2375 female athletes; 87 % of the male and 29 % of the female were professional athletes. 7 usable publications with a total of 8011 h. e. in men and 6 publications with 1055 h. e. in women dealt with contact/non-contact genesis of h. e.. 46 % male (72 % female) athletes suffered from h. e. caused by contact events, and 54 % male (28 % female) athletes suffered from h. e. caused by non-contact events. The distribution of acute and overuse injuries was analysed in 9969 h. e. in men (11 publications), and in 624 h. e. in women (5 publications). On average, the number of acute injuries (90 % male, 86 % female) was much higher than that of overuse injuries. The prevalence of h. e. with respect to training or match playing was analysed in 11 studies with 10 078 h. e. in men, and in 4 studies with 546 harmful events in women. 35 % of men's h. e. occurred during training and 65 % during matches, whereas 60 % of the women's h. e. occurred during training and 40 % during matches. CONCLUSION: The number of athletes included in the studies is quite low in relation to the number of active athletes. Studies of professional athletes are over-represented. Independent of gender, there are more acute injuries than overuse injuries, whereas the distribution of harmful events with respect to genesis and occurrence during training and match is gender-specific. The studies' evidence level is quite low in relation to the socio-economic significance of this kind of sport; the studies' evidence is higher for women.

Determinants of health among homeless population in the Czech Republic--an empirical study.

It is generally recognized, that the delivery of healthcare to homeless population presents a number of specific challenges. In this paper, we try to assess the impact of the homeless people experience with the institutional framework including the access to health services on the health status of the homeless population in the Czech Republic. Multivariate regression is used to evaluate the impact of various dimensions of life experience and other social and economic characteristics of homeless people on their health status. Preliminary results indicate that the experience homeless people have with the institutional framework and their access to health care services are important determinants of their health status.

Cyclin-dependent kinase inhibition by new C-2 alkynylated purine derivatives and molecular structure of a CDK2-inhibitor complex.

A new series of 2,6,9-trisubstituted purines, characterized by the presence of a common alkynyl substituent at C-2 and a range of different anilino/benzylamino groups at C-6, were synthesized. These compounds were evaluated for their capacity to inhibit cyclin-dependent kinase activity (CDK1-cyclin B) in vitro. Compounds 4e (N-6-p-Cl-benzylamino derivative) and 5e (N-6-m-Cl-anilino derivative) exhibited the strongest inhibitory activity with an IC(50) of 60 nM. The structure of compound 4b (N-6-p-methoxybenzylamino derivative) in complex with human CDK2 was determined by X-ray crystallography, revealing the molecular basis of inhibition by this molecule. Subsequent molecular modeling studies allowed us to rationalize the SAR observed for these compounds.

Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors.

Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 microM, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50-6.7 microM versus 42.7 microM for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50= 25.3 microM, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells. olomoucilnc and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible hlock in GI and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chmronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minour amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nuicleosides with high efficiency.

Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases.

The synthesis of a new family of inhibitors of the cell cycle regulating cyclin-dependent kinases (CDK's) is reported. These compounds, related to the purines olomoucine and roscovitine, are characterised by the presence of alkynylated side chains at C2. They inhibit CDK's with IC50's in the 200 nM range.

A new mechanism in serine proteases catalysis exhibited by dipeptidyl peptidase IV (DP IV)--Results of PM3 semiempirical thermodynamic studies supported by experimental results.

Herein we present results of semiempirical molecular orbital calculations employing the PM3 molecular model. The compounds studied are related to substrates of the serine protease dipeptidyl peptidase IV (DP IV). Our goal was the thermodynamic characterization of the DP IV-enzyme-catalyzed reaction pathway. A new mechanism of serine proteases catalysis is presented. We found that a tetrahedral intermediate can be stabilized by the formation of an oxazolidine ring with the nonscissile P2-P1 peptide bond. In this way, the negative charge of the tetrahedral intermediate around the scissile bond is transferred to the carbonyl oxygen atom of the preceding peptide bond. This negative charge can be compensated by a proton transfer from the positively charged N-terminus to this oxygen atom. It is shown that the positively charged N-terminus is the driving force in this particular serine protease mechanism of catalysis. The mechanism is supported by observed secondary hydrogen isotope effects on the C alpha proton for an alanine residue in the P2 position. We suggest a trans-cis isomerisation around the P2-P1 peptide bond in the final step of the acylation and cleavage of the substrates. The results obtained by our theoretical calculations are compared with several experimental findings supporting the suggested mechanism.

[Automobile driving studies to determine alcohol-induced driving insecurity after dark]. / Pkw-Fahrversuche zur Frage der alkoholbedingten Fahrunsicherheit bei Dunkelheitsfahrten.

To further elucidate the question whether the criteria for assessing alcohol-induced unfitness to drive should be stricter for night-time than for day-time driving (cf. Schewe et al., 1977) 64 test persons performed automobile driving tests in daylight and in darkness while being sober and while under the influence of alcohol. The first set of tests was done in daylight. A test course of approx. 600 m involving six everyday driving maneuvers had to be covered, first in the sober state and then at blood alcohol concentrations (BAC) of 1.1 g % and 1.4 g %. The driving tests in the dark were performed on the same test course, first in the sober state and then at a BAC of 1.1 g%. In both test series the errors were counted and the driving times measured. Statistical evaluation of the test results was done parametrically (t-test for dependent random samples) and distribution-free (Wilcoxon's test for paired comparison). In the sober state 2.1 errors were made on average during the day and 3.2 errors, i.e. one error more, at night. At 1.1 g %, 4.3 errors occurred during the day but 8.0 errors at night (i.e. 3.7 errors more than during the day). The differences were statistically significant. With 8 errors during night-time driving at 1.1 g % the number of errors was still higher than the average number of 6.8 errors made during day-time driving at 1.4 g %. The average driving times required in the sober state were 241 s during the day and 256 s at night. At 1.1 g %, 243 s were needed during the day and 272 s at night, i.e. on average 17 s more than for day-time driving at 1.4 g % for which 255 s were needed. For an orienting comparison of driving performance it can be assumed that "performance" in the sense meant here is reciprocally proportional to the number of errors and reciprocally proportional to the time required, i.e. on the whole reciprocally proportional to the product from number of errors and time. The deterioration of performance can be illustrated best by assuming performance in the sober state during the day to be 100% and relating the other "performances" thereto.(ABSTRACT TRUNCATED AT 250 WORDS)

[Forensic value of analytic results from less than 5 (4) blood alcohol values of a blood sample]. / Zur forensischen Verwertbarkeit der Analysenergebnisse von weniger als fünf (vier) Blutalkoholbestimmungen aus einer Blutprobe.

1. If the material for blood-alcohol examinations is insufficient under the existing regulations (specification in the GUTACHTEN DES BUNDESGESUNDHEITSAMTES) it is possible to determine the mean value almost certainly, estimating the confidence-interval. This mean value can be taken as basis of the opinion with regard to safe driving. 2. The proposed statistical procedure is described and compared with other suggested calculations. 3. Testing the proposed procedure by means of 1,426 real data, the usefulness of the proposed calculation is shown.

Porin of Paramecium mitochondria isolation, characterization and ion selectivity of the closed state.

Porin was isolated and purified from mitochondria of Paramecium tetraurelia. The protein showed a single band of apparent Mr 37,000 on sodium dodecyl sulfate polyacrylamide electrophoretograms. The reconstitution of the protein into artificial lipid bilayer membranes revealed it to be a porin giving pores with an average single-channel conductance of 0.26 nS in 0.1 M KCl. This conductance is about half of that of other eukaryotic porins studied to date. The pore formed by the mitochondrial porin of Paramecium was found to be voltage-dependent and switched to a defined substrate at membrane voltages larger than 20 mV. In the open state the pore exhibited the characteristics of a general diffusion pore because the mobility sequence of the ions inside the pore was similar to that in the bulk aqueous phase. The effective diameter was estimated to be about 1.3 nm. The properties of the low conductance state of the pore were studied in detail. In this state the pore favored the passage of cations, in contrast to the open state which favored anions slightly. The possible role of the low-conductance state in the regulation of transport processes across the outer mitochondrial membrane and in mitochondrial metabolism is discussed.

Purification and characterization of the pore forming protein of yeast mitochondrial outer membrane.

One of the major outer membrane proteins of yeast mitochondria was isolated and purified. It migrated as a single band with an apparent molecular weight of 30 kDa on a SDS-electrophoretogram. When reconstituted in lipid bilayer membranes the protein formed pores with a single channel conductance of 0.45 nS in 0.1 M KCl. The pores had the characteristics of general diffusion pores with an estimated diameter of 1.7 nm. The pore of mitochondrial outer membranes of yeast shared some similarities with the pores formed by mitochondrial and bacterial porins. The pores switched to substates at voltages higher than 20 mV. The possible role of this voltage-dependence in the metabolism of mitochondria is discussed.