Impact of elite soccer coaching change on team performance according to coach- and club-related variables

A coaching change is an extreme, but frequently occurring phenomenon in elite soccer with its impact on team success debatable. The aim of the current study was twofold: (i) to compare team’s performance when coached by new and old coaches; and (ii) to investigate the impact of a coaching change on team’s performance according to coach- and club-related factors. All in-season coaching changes from the 2010–11 to 2017–18 seasons within the Spanish, French, English, German and Italian professional leagues were examined. Team performance was assessed as points awarded from match outcome over 1–20 matches prior to and following the coaching change. Four independent variables (coach’s experience, team’s budget, whether the coach had been an elite former player or not, and whether the coach was a novice or not) were included into linear regression modelling. The main results showed that team’s short-term performance was improved significantly with a change to a new coach with this impact declining in the longer term (> 10 matches). Specifically, the number of points (1.15–1.32 vs. 0.37–1.03, p < 0.05) and the moving average of points (1.19–1.31 vs. 0.37–1.04, p < 0.05) awarded per match were significantly greater after the coaching change. Further, the winning effect due to the new coach was independent of coach-related factors such as coaching experience or the new coach being a former elite player. A critical organisational decision to change coaches may provide an essential stimulus for future team success in elite soccer.     

How Psychological and Behavioral Team States Change during Positive and Negative Momentum

In business and sports, teams often experience periods of positive and negative momentum while pursuing their goals. However, researchers have not yet been able to provide insights into how psychological and behavioral states actually change during positive and negative team momentum. In the current study we aimed to provide these insights by introducing an experimental dynamical research design. Rowing pairs had to compete against a virtual opponent on rowing ergometers, while a screen in front of the team broadcasted the ongoing race. The race was manipulated so that the team’s rowing avatar gradually progressed (positive momentum) or regressed (negative momentum) in relation to the victory. The participants responded verbally to collective efficacy and task cohesion items appearing on the screen each minute. In addition, effort exertion and interpersonal coordination were continuously measured. Our results showed negative psychological changes (perceptions of collective efficacy and task cohesion) during negative team momentum, which were stronger than the positive changes during positive team momentum. Moreover, teams’ exerted efforts rapidly decreased during negative momentum, whereas positive momentum accompanied a more variable and adaptive sequence of effort exertion. Finally, the interpersonal coordination was worse during negative momentum than during positive momentum. These results provide the first empirical insights into actual team momentum dynamics, and demonstrate how a dynamical research approach significantly contributes to current knowledge on psychological and behavioral processes.     

The Relationship Between the Tumor Cell Expression of Hypoxic Markers and Survival in Patients With ER-positive Invasive Ductal Breast Cancer

The prognostic significance of hypoxia markers, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and carbonic anhydrase IX (CAIX), was investigated in estrogen receptor (ER)-positive breast cancer patients. Immunohistochemistry determined the expression of makers in two independent ductal ER-positive cohorts (Training set, n=373 and Validation set, n=285) and was related to clinicopathological parameters and disease-free survival (DFS). In the training cohort, nuclear HIF-1α (1) was independently associated with poorer DFS in luminal A tumors [hazard ratio (HR) = 0.53 95% confidence interval (CI): 0.30–0.94, p=0.030]. In the validation cohort, both HIF-1α (1) and CAIX were independently associated with decreased DFS in the entire cohort (HR = 1.85 95% CI: 1.10–3.11, p=0.019; HR = 1.74 95% CI: 1.08–2.82, p=0.023), in luminal A disease (HR = 1.98 95% CI: 1.02–3.83, p=0.042), and in luminal B disease (HR = 2.75 95% CI: 1.66–4.55, p<0.001), respectively. Taken together, elevated cytoplasmic HIF-1α (1) expression was an independent prognostic factor in luminal A disease, whereas CAIX was an independent prognostic factor in luminal B disease. Further work in large tissue cohorts is required.     

Monitoring external load in elite male handball players depending on playing positions

Monitoring workload is critical for elite training and competition, as well as preventing potential sports injuries. The assessment of external load in team sports has been provided with new technologies that help coaches to individualize training and optimize their team’s playing system. In this study we characterized the physical demands of an elite handball team during an entire sports season. Novel data are reported for each playing position of this highly strenuous body-contact team sport. Sixteen world top players (5 wings, 2 centre backs, 6 backs, 3 line players) were equipped with a local positioning system (WIMU PRO) during fourteen official Spanish first league matches. Playing time, total distance covered at different running speeds, and acceleration variables were monitored. During a handball match, wings cover the greater distance by high-speed running (> 5.0 m·s^-1): 410.3 ± 193.2 m, and by sprint (> 6.7 m·s^-1): 98.0 ± 75.4 m. Centre backs perform the following playing position that supports the highest speed intensities during the matches: high-speed running: 243.2 ± 130.2 m; sprint: 62.0 ± 54.2 m. Centre backs also register the largest number of high-intensity decelerations (n = 142.7 ± 59.5) compared to wings (n = 112.9 ± 56.0), backs (n = 105.2 ± 49.2) and line players: 99.6 ± 28.9). This study provides helpful information for professional coaches and their technical staff to optimize training load and individualize the physical demands of their elite male handball players depending on each playing position.     

Players’ physical performance in LaLiga across the season: insights for competition continuation after COVID-19

Due to the COVID-19 outbreak, professional football players competing in LaLiga were confined at home for ~8 weeks and then they were allowed to train to prepare the first competitive match for 4 weeks. As the duration of summer break in the prior four seasons of LaLiga (from 2015-2016 to 2018-2019) was of similar length to the suspension of the championship due to COVID-19 (~12 weeks), we have analysed the running performance of teams competing in LaLiga in these four seasons to anticipate players’ physical performance after the resumption of the competition. The analysis includes the average running distance per game for each of the 38 matchdays that compose LaLiga. One-way ANOVA revealed that there was a main effect of the matchday on total running distance per match (p = 0.001), and in the distance covered between 14.0 and 20.9 km/h (p < 0.001), between 21.0 and 23.9 km/h (p < 0.001) and at above 24.0 km/h (p < 0.001). Overall, the post-hoc analysis revealed that the running patterns progressively increased during the first 8-10 matchdays and then reached a plateau which was significantly different to matchday-1 (p < 0.05). This analysis reveals that, in the prior four competitive seasons of LaLiga, players’ physical performance was lower at the beginning of the season and the teams needed approximately 8-10 matchdays to reach a steady state running performance. These data suggest that football players will progressively increase their performance across the 11 matchdays remaining to complete LaLiga.     

Association of Six Well-Characterized Polymorphisms in TNF-α and TNF-β Genes with Sarcoidosis: A Meta-Analysis

Backgrounds

In this study, we aimed to investigate the association of six well-characterized polymorphisms in tumor necrosis factor alpha and beta (TNF-α and TNF-β) genes with the risk for sarcoidosis via a comprehensive meta-analysis.

Methods And Findings

The electronic MEDLINE (Ovid) and PubMed databases covering the period from the earliest possible year to June 2013 were searched. Total 13 qualified articles including 1584 patients with sarcoidosis and 2636 controls were recruited. The data were analyzed by RevMan software, and risk estimates were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses of the full data set failed to identify any significant association of TNF-α gene -307A (OR=1.25; 95% CI: 0.98-1.59), -1031C (OR=0.88; 95% CI: 0.71-1.1), -863A (OR=0.89; 95% CI: 0.72-1.11), -238A (OR=0.97; 95% CI: 0.71-1.32), and -857T (OR=1.14; 95% CI: 0.74-1.77) alleles, but a significant association for TNF-β 252A allele (OR=1.65; 95%CI = 1.33-2.04; P<0.00001). Under a random-effects allelic model, there was marginally significant increased risk of sarcoidosis for -307A allele among Caucasians (OR=1.25; 95% CI: 0.96-1.62; P=0.09) but not among Asians (OR=2.12; 95% CI: 0.31-14.27; P=0.44). There was a low probability of publication bias as reflected by the fail-safe number.

Conclusions

This meta-analysis extended previous findings on the association between the TNF-α and TNF-β genetic polymorphisms and sarcoidosis, by showing that the TNF-β gene A252G polymorphism might be a potential risk factor for the development of sarcoidosis.     

A meta-analysis reveals the effectiveness of probiotics and prebiotics against respiratory viral infection

Experimental experience suggests that microbial agents including probiotics and prebiotics (representative microbial agents) play a critical role in defending against respiratory virus infection. We aim to systematically examine these agents’ effect on respiratory viral infection and encourage research into clinical applications. An electronic literature search was conducted from published data with a combination of a microbial agents search component containing synonyms for microbial agents-related terms and a customized search component for respiratory virus infection. Hazard ratio (HR), risk ratio (RR) and standard deviation (SD) were employed as effect estimates. In 45 preclinical studies, the mortality rates decreased in the respiratory viral infection models that included prebiotics or prebiotics as interventions (HR: 0.70; 95% confidence interval (CI): 0.56–0.87; P=0.002). There was a significant decrease in viral load due to improved gut microbiota (SD: −1.22; 95% CI: −1.50 to −0.94; P<0.001). Concentrations of interferon (IFN)-α (SD: 1.05; 95% CI: 0.33–1.77; P=0.004), IFN-γ (SD: 0.83; 95% CI: 0.01–1.65; P=0.05) and interleukin (IL)-12 (SD: 2.42; 95% CI: 0.32–4.52; P=0.02), IL-1β (SD: 0.01; 95% CI: −0.37 to 0.40; P=0.94) increased, whereas those of TNF-α (SD: −0.58; 95% CI: −1.59 to 0.43; P=0.26) and IL-6 (SD: −0.59; 95% CI: −1.24 to 0.07; P=0.08) decreased. Six clinical studies had lower symptom scores (SD: −0.09; 95% CI: −0.44 to 0.26; P=0.61) and less incidence of infection (RR: 0.80; 95% CI: 0.64–1.01; P=0.06). Our research indicates that probiotics and prebiotics pose a defensive possibility on respiratory viral infection and may encourage the clinical application.     

Apolipoprotein E Gene Variants on the Risk of End Stage Renal Disease

Objective

End-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between apoE gene polymorphisms and ESRD susceptibility.

Methods

Databases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies.

Results

Sixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15–1.46, P < 0.0001; I ² = 18%, P for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31–2.10, P < 0.0001; OR = 1.62, 95% CI 1.31–2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant.

Conclusion

The ε2 allele of apoE gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.     

Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches

BackgroundHealth care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence.MethodsA multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software.ResultsThe emerging programme theory highlighted the importance of the combination of each team’s self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence.ConclusionsInterventions to improve primary health care teams’ response to intimate partner violence should focus on strengthening team’s self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working experience in primary health care, and other factors such as training, a good team climate, and having a champion social worker on the team, also played a key role. Measures to sustain such interventions and promote these contextual factors should be encouraged.     

A Method for Using Player Tracking Data in Basketball to Learn Player Skills and Predict Team Performance

Player tracking data represents a revolutionary new data source for basketball analysis, in which essentially every aspect of a player’s performance is tracked and can be analyzed numerically. We suggest a way by which this data set, when coupled with a network-style model of the offense that relates players’ skills to the team’s success at running different plays, can be used to automatically learn players’ skills and predict the performance of untested 5-man lineups in a way that accounts for the interaction between players’ respective skill sets. After developing a general analysis procedure, we present as an example a specific implementation of our method using a simplified network model. While player tracking data is not yet available in the public domain, we evaluate our model using simulated data and show that player skills can be accurately inferred by a simple statistical inference scheme. Finally, we use the model to analyze games from the 2011 playoff series between the Memphis Grizzlies and the Oklahoma City Thunder and we show that, even with a very limited data set, the model can consistently describe a player’s interactions with a given lineup based only on his performance with a different lineup.     

Parp mutations protect from mitochondrial toxicity in Alzheimer’s disease

Alzheimer’s disease is the most common age-related neurodegenerative disorder. Familial forms of Alzheimer’s disease associated with the accumulation of a toxic form of amyloid-β (Aβ) peptides are linked to mitochondrial impairment. The coenzyme nicotinamide adenine dinucleotide (NAD⁺) is essential for both mitochondrial bioenergetics and nuclear DNA repair through NAD⁺-consuming poly (ADP-ribose) polymerases (PARPs). Here we analysed the metabolomic changes in flies overexpressing Aβ and showed a decrease of metabolites associated with nicotinate and nicotinamide metabolism, which is critical for mitochondrial function in neurons. We show that increasing the bioavailability of NAD⁺ protects against Aβ toxicity. Pharmacological supplementation using NAM, a form of vitamin B that acts as a precursor for NAD⁺ or a genetic mutation of PARP rescues mitochondrial defects, protects neurons against degeneration and reduces behavioural impairments in a fly model of Alzheimer’s disease. Next, we looked at links between PARP polymorphisms and vitamin B intake in patients with Alzheimer’s disease. We show that polymorphisms in the human PARP1 gene or the intake of vitamin B are associated with a decrease in the risk and severity of Alzheimer’s disease. We suggest that enhancing the availability of NAD⁺ by either vitamin B supplements or the inhibition of NAD⁺-dependent enzymes such as PARPs are potential therapies for Alzheimer’s disease.Subject terms: Metabolomics, Cell death in the nervous system, Alzheimer''s disease     

External match load and the influence of contextual factors in elite futsal

Quantifying external load during futsal competition can provide objective data for the management of the athlete’s performance and late-stage rehabilitation. This study aimed to report the match external load collected via wearable technology according to time periods (i.e., halves) and contextual factors (i.e., team’s ranking, match result, and location) in elite futsal. Nine professional male players used a GPS-accelerometer unit during all games of the 2019–2020 season. Player load (PL), PL·min^-1, high-intensity acceleration (ACC_HI), deceleration (DEC_HI), explosive movements (EXPL-MOV), and change of direction (COD_HI) data were collected. On average, players displayed values of: total PL 3868 ± 594 a.u; PL·min^-1: 10.8 ± 0.8 a.u; number of ACC_HI: 73.3 ± 13.8, DEC_HI: 68.6 ± 18.8, EXPL-MOV: 1165 ± 188 and COD_HI: 173 ± 29.1. A moderate and significant decrease was found in the 2^nd half for total PL (p = 0.03; ES = 0.52), PL·min^-1 (p = 0.001; ES = 1.16), DEC_HI (p = 0.001; ES = 0.83), and EXPL-MOV (p = 0.017; ES = 0.58) compared to the 1^st half. Small and nonsignificant differences were found between contextual factors. In summary, this study indicates that futsal players are exposed to high-intensity mechanical external loads, and perform a great number of ACC_HI, DEC_HI, EXPL-MOV and COD_HI, without being influenced by the team ranking, result and match location. Coaches and sports scientists are advised to implement speed-power, DEC, and COD activities in the training sessions, and may use these reference values to design specific training and return-to-play plans.     

Associations between women’s empowerment and child development,growth, and nurturing care practices in sub-Saharan Africa: A cross-sectional analysis of demographic and health survey data

BackgroundApproximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women’s empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women’s empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA).Methods and findingsWe pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women’s empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy–numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ <−2). Early learning outcomes were number of parental stimulation activities (range 0 to 6) and learning resources (range 0 to 4). The nutrition outcome was child dietary diversity score (DDS, range 0 to 7). We assessed the relationship between women’s empowerment and child development, growth, early learning, and nutrition using multivariate generalized linear models.On average, households in our sample were large (8.5 ± 5.7 members) and primarily living in rural areas (71%). Women were 31 ± 6.6 years on average, 54% had no education, and 31% had completed primary education. Children were 47 ± 7 months old and 49% were female. About 23% of children had suboptimal cognitive development, 31% had suboptimal socioemotional development, and 90% had suboptimal literacy–numeracy development. Only 9% of children had suboptimal physical development, but 35% were stunted. Approximately 14% of mothers and 3% of fathers provided ≥4 stimulation activities. Relative to the lowest quintile category, children of women in the highest empowerment quintile category were less likely to have suboptimal cognitive development (relative risk (RR) 0.89; 95% confidence interval (CI) 0.80, 0.99), had higher HAZ (mean difference (MD) 0.09; 95% CI 0.02, 0.16), lower risk of stunting (RR 0.93; 95% CI 0.87, 1.00), higher DDS (MD 0.17; 95% CI 0.06, 0.29), had 0.07 (95% CI 0.01, 0.13) additional learning resources, and received 0.16 (95% CI 0.06, 0.25) additional stimulation activities from their mothers and 0.23 (95% CI 0.17 to 0.29) additional activities from their fathers. We found no evidence that women’s empowerment was associated with socioemotional, literacy–numeracy, or physical development. Study limitations include the possibility of reverse causality and suboptimal assessments of the outcomes and exposure.ConclusionsWomen’s empowerment was positively associated with early child cognitive development, child growth, early learning, and nutrition outcomes in SSA. Efforts to improve child development and growth should consider women’s empowerment as a potential strategy.

Lilia Bliznashka and co-workers study empowerment of women and associated child health outcomes in sub-Saharan Africa.     

Creatine and creatinine quantification in olympic athletes: dried blood spot analysis pilot study

Capillary dried blood spot (DBS) samples facilitate field-based collection without venipuncture. This pilot study aims to evaluate the viability of creatine (Cr) and creatinine (Crt) quantification using fresh capillary serum (Cr_S/Crt_S) and DBS samples (Cr_DBS/Crt_DBS), using Flow Injection Analysis Mass Spectrometry (FIA – MS). Nine Olympic Athletes provided a capillary blood sample to assess Cr_S/Crt_S and Cr_DBS/Crt_DBS quantified by FIA – MS. No difference between Crt_S (mean ± SD: 813.6 ± 102.4 μmol/L) and Crt_DBS (812.4 ± 108.1 μmol/L) was observed with acceptable variance [SEM 88.7; CV 10.7%; ICC 0.57 (CI 95% 0.06 – 0.84)] and agreement [very strong (Spearman: r = 0.77; p < 0.01) or strong (Pearson: r = 0.56; p = 0.04); Bland Altman: lower (-193) and upper (+196) limits of agreement]. Cr_S (mean ± SD: 691.8 ± 165.2 μmol/L) was significantly different to Cr_DBS (2911 ± 571.4 μmol/L) with unacceptable variance [SEM 171.6; CV 27%; ICC 0.002 (CI 95% -0.02 – 0.07)] and ‘weak’ agreement [Spearman: r = 0.21, p = 0.47 and Pearson: r = 0.06, p = 0.84; Bland Altman lower (-3367) and upper (-1072) limits of agreement]. Crt quantification is viable using both Crt_S and Crt_DBS (but not for Cr and Cr_S/Cr_DBS), with the DBS tissue handling technique offering several methodological and practice facing advantages. Future work should expand upon the sample size, explore sport/discipline relevant analytes across a full competitive season, including key training, recovery and performance blocks of their periodized performance plan.     

The impact of COVID-19 lockdown on professional soccer players’ body composition and physical fitness

During the COVID-19 lockdown, professional soccer players ceased their regular team training sessions and were provided with exercise programs to follow independently. This investigation assessed the impact of a 7-week COVID-19 lockdown and home-based individual physical training on professional soccer players’ body composition and physical fitness. The study consisted of nineteen division 1 elite soccer players (age 27.68 ± 5.99 years, height 178.47 ± 5.44 cm) and compared the anthropometric and physical fitness parameters obtained post-transition period to those obtained post-COVID-19 lockdown. The statistical analysis indicated that body fat percentage was significantly higher after the lockdown period [t(18) = -5.59, p < 0.01, d = 0.56]. Furthermore, VO_2max [t(17) = -11.54, p < 0.01, d = 0.57] and running time [t(17) = 3.94, p < 0.01, d = 0.76] values were significantly higher after the COVID-19 lockdown than those obtained after the transition period. In addition, significantly higher level of performance was demonstrated on squat jump [t(18) = -4.10, p < 0.01, d = 0.30], countermovement jump [t(18) = -7.43, p < 0.01, d = 1.11] and sit and reach tests [t(19) = -5.33, p < 0.01, d = 0.32]. Concurrently, lower body strength was indicated to be significantly greater (p < 0.01) following the COVID-19 lockdown. The training protocol provided during the confinement, due to the COVID-19 outbreak, was effective in keeping physical fitness at a significantly higher level compared to the transition period. Coaches and trainers are encouraged to examine the effectiveness of this protocol, as it may help them develop effective periodization programs during the transition period. This protocol may aid in the development of effective periodization programs that require minimal equipment and can be followed in similar situations.     

Evidence for the emergence of β-trefoils by ‘Peptide Budding’ from an IgG-like β-sandwich

As sequence and structure comparison algorithms gain sensitivity, the intrinsic interconnectedness of the protein universe has become increasingly apparent. Despite this general trend, β-trefoils have emerged as an uncommon counterexample: They are an isolated protein lineage for which few, if any, sequence or structure associations to other lineages have been identified. If β-trefoils are, in fact, remote islands in sequence-structure space, it implies that the oligomerizing peptide that founded the β-trefoil lineage itself arose de novo. To better understand β-trefoil evolution, and to probe the limits of fragment sharing across the protein universe, we identified both ‘β-trefoil bridging themes’ (evolutionarily-related sequence segments) and ‘β-trefoil-like motifs’ (structure motifs with a hallmark feature of the β-trefoil architecture) in multiple, ostensibly unrelated, protein lineages. The success of the present approach stems, in part, from considering β-trefoil sequence segments or structure motifs rather than the β-trefoil architecture as a whole, as has been done previously. The newly uncovered inter-lineage connections presented here suggest a novel hypothesis about the origins of the β-trefoil fold itself–namely, that it is a derived fold formed by ‘budding’ from an Immunoglobulin-like β-sandwich protein. These results demonstrate how the evolution of a folded domain from a peptide need not be a signature of antiquity and underpin an emerging truth: few protein lineages escape nature’s sewing table.     

Sprint Conditioning of Junior Soccer Players: Effects of Training Intensity and Technique Supervision

The aims of the present study were to compare the effects of 1) training at 90 and 100% sprint velocity and 2) supervised versus unsupervised sprint training on soccer-specific physical performance in junior soccer players. Young, male soccer players (17 ±1 yr, 71 ±10 kg, 180 ±6 cm) were randomly assigned to four different treatment conditions over a 7-week intervention period. A control group (CON, n=9) completed regular soccer training according to their teams’ original training plans. Three training groups performed a weekly repeated-sprint training session in addition to their regular soccer training sessions performed at A) 100% intensity without supervision (100UNSUP, n=13), B) 90% of maximal sprint velocity with supervision (90SUP, n=10) or C) 90% of maximal sprint velocity without supervision (90UNSUP, n=13). Repetitions x distance for the sprint-training sessions were 15x20 m for 100UNSUP and 30x20 m for 90SUP and 90UNSUP. Single-sprint performance (best time from 15x20 m sprints), repeated-sprint performance (mean time over 15x20 m sprints), countermovement jump and Yo-Yo Intermittent Recovery Level 1 (Yo-Yo IR1) were assessed during pre-training and post-training tests. No significant differences in performance outcomes were observed across groups. 90SUP improved Yo-Yo IR1 by a moderate margin compared to controls, while all other effect magnitudes were trivial or small. In conclusion, neither weekly sprint training at 90 or 100% velocity, nor supervised sprint training enhanced soccer-specific physical performance in junior soccer players.     

TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children

Background

TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner.

Methods

511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence).

Results

Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations.

Conclusion

TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk.     

Impact of Three Oral Antidiabetic Drugs on Markers of β-Cell Function in Patients with Type 2 Diabetes: A Meta-Analysis

Background

The effect of metformin, pioglitazone and sitagliptin on β-cell function in the treatment of type 2 diabetes is controversial. Therefore, we performed a systematic review and meta-analysis to obtain a better understanding in the β-cell effects of metformin, pioglitazone and sitagliptin.

Methods

We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on β-cell function were identified. The primary outcomes were homeostasis model assessment of β-cells (HOMA-β) and proinsulin/insulin ratio (PI/IR). Secondary outcome was hemoglobin A1c level. We used version 2 of the Comprehensive Meta Analysis software for all statistical analyses.

Results

Metformin monotherapy was more effective than sitagliptin in improving HOMA-β (18.01% (95% CI 11.09% to 24.94%) vs. 11.29% (95% CI 9.21% to 13.37%), P = 0.040) and more effective (−0.137 (95% CI −0.082 to −0.192)) than both sitagliptin (−0.064 (95% CI −0.036 to −0.092), P = 0.019) and pioglitazone (−0.068 (95% CI −0.044 to −0.093), P = 0.015) in decreasing PI/IR. Metformin and sitagliptin combined (40.23% (95%CI 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82% (95% CI 6.61% to 17.04%), P = 0.000) and pioglitazone and metformin(9.81% (95% CI 1.67% to 17.95%), P = 0.022) in improving HOMA-β and decreasing PI/IR (−0.177 (95% CI −0.118 to −0.237); −0.080 (95% CI −0.045 to −0.114), P = 0.007; −0.038 (95% CI, −0.005 to 0.071), P = 0.023).

Limitations

The included RCTs were of short duration (12–54 weeks). We could not determine long term effects on β-cells.

Conclusions

Metformin improves β-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-β and PI/IR more than other combinations.     

Functional Dissection of the Nascent Polypeptide-Associated Complex in Saccharomyces cerevisiae

Both the yeast nascent polypeptide-associated complex (NAC) and the Hsp40/70-based chaperone system RAC-Ssb are systems tethered to the ribosome to assist cotranslational processes such as folding of nascent polypeptides. While loss of NAC does not cause phenotypic changes in yeast, the simultaneous deletion of genes coding for NAC and the chaperone Ssb (nacΔssbΔ) leads to strongly aggravated defects compared to cells lacking only Ssb, including impaired growth on plates containing L-canavanine or hygromycin B, aggregation of newly synthesized proteins and a reduced translational activity due to ribosome biogenesis defects. In this study, we dissected the functional properties of the individual NAC-subunits (α-NAC, β-NAC and β’-NAC) and of different NAC heterodimers found in yeast (αβ-NAC and αβ’-NAC) by analyzing their capability to complement the pleiotropic phenotype of nacΔssbΔ cells. We show that the abundant heterodimer αβ-NAC but not its paralogue αβ’-NAC is able to suppress all phenotypic defects of nacΔssbΔ cells including global protein aggregation as well as translation and growth deficiencies. This suggests that αβ-NAC and αβ’-NAC are functionally distinct from each other. The function of αβ-NAC strictly depends on its ribosome association and on its high level of expression. Expression of individual β-NAC, β’-NAC or α-NAC subunits as well as αβ’-NAC ameliorated protein aggregation in nacΔssbΔ cells to different extents while only β-NAC was able to restore growth defects suggesting chaperoning activities for β-NAC sufficient to decrease the sensitivity of nacΔssbΔ cells against L-canavanine or hygromycin B. Interestingly, deletion of the ubiquitin-associated (UBA)-domain of the α-NAC subunit strongly enhanced the aggregation preventing activity of αβ-NAC pointing to a negative regulatory role of this domain for the NAC chaperone activity in vivo.