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We generated two human induced pluripotent cell (hiPSC) isogenic clones from an 11-year-old patient with 6q27 deletion syndrome. The heterozygous deletion encompasses approximately 240 kilobases, affecting 6 genes (promoter region of WDR27, coding regions of C6orf120, PHF10, DYNLT2, ERMARD, LINC00242). The patient suffered from epilepsy, psychosocial retardation, and a metabolic disorder. The patient also had a history of SHH-medulloblastoma as an infant. The generated hiPSCs represent a useful tool for modelling 6q27 deletion syndrome in vitro and understanding the molecular basis of the disorder.

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Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown. To explore the role of Elp1 in the cerebellum, we knocked out Elp1 in cerebellar granule cell progenitors (GCPs) and examined the outcome on animal behavior and cellular composition. We found that GCP-specific conditional knockout of Elp1 (Elp1cKO) resulted in ataxia by 8 weeks of age. Cellular characterization showed that the animals had smaller cerebella with fewer granule cells. This defect was already apparent as early as 7 days after birth, when Elp1cKO animals also had fewer mitotic GCPs and shorter Purkinje dendrites. Through molecular characterization, we found that loss of Elp1 was associated with an increase in apoptotic cell death and cell stress pathways in GCPs. Our study demonstrates the importance of ELP1 in the developing cerebellum, and suggests that loss of Elp1 in the GC lineage may also play a role in the progressive ataxia phenotypes of FD patients.

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The triathlon Mixed-Team-Relay (MTR) is a new race format present for the first time at the Tokyo Olympic Games in 2021. The results of the ITU Triathlon Mixed Relay World Championship from 2014 to 2019 were collected to provide practical suggestions for forming a successful MTR, such as the importance of each leg and discipline on MTR and Super-Sprint performance. The total relay time (Trelay), the time of each team member (leg-from 1 to 4) (Tleg), and the time of each single discipline (swim, T1, cycle, T2, run) were collected from the official website. Inferential analysis was performed to assess prediction and differences between variables. Leg 3 was shown to be the most important to predict Trelay (0.41), which is also the slower. For both Trelay and Tleg, cycling resulted as the most important (>0.60) and longer (~52%) portion, followed by running and swimming. However, higher importance in swimming was found in successful teams compared to running. For a successful MTR, we suggest: (a) use short-distance specialized triathletes; (b) strengthen cycling and swimming; (c) position in legs 1 and 2 athletes capable of racing in a group; in legs 3 and 4 athletes capable of racing in a non-drafting situation.

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BACKGROUND: Induction of labor is one of the most common interventions in modern obstetrics, and its frequency is expected to continue to increase. There is inconsistency as to how failed induction of labor is defined; however, the majority of studies define success as the achievement of vaginal delivery. Induction of labor in nulliparous women poses an additional challenge with a 15% to 20% incidence of failure, ending in emergency operative deliveries. The Bishop score has been traditionally used before decisions for induction of labor. Nonetheless, it is subjective and prone to marked interobserver variation. Several studies have been conducted to find alternative predictors, yet a reliable, objective method still remains to be introduced and validated. Hence, there is still a need for the development of new predictive tools to facilitate informed decision making, optimization of resources, and minimization of potential risks of failure. Furthermore, a peripartum transperineal ultrasound scan has been proven to provide objective, noninvasive assessment of labor. OBJECTIVE: This study aimed to assess the feasibility of developing and validating an objective and reproducible model for the prediction of cesarean delivery for failure to progress as an outcome of labor induction in term singleton pregnancies. STUDY DESIGN: This was a prospective observational cohort study conducted in Cairo University Hospitals and University of Bologna Hospitals between November 2018 and November 2019. We recruited 382 primigravidae with singleton term pregnancies in cephalic presentation. All patients had baseline Bishop scoring together with various transabdominal and transperineal ultrasound assessments of the fetus, maternal cervix, and pelvic floor. The managing obstetricians were blinded to the ultrasound scan findings. The method and indication of induction of labor, the total duration of stages of labor, mode of birth, and neonatal outcomes were all recorded. Women who had operative delivery for fetal distress or indications other than failure to progress in labor were excluded from the final analysis, leaving a total of 344 participants who were randomly divided into 243 and 101 pregnancies that constituted the model development and cross-validation groups, respectively. RESULTS: It was possible to perform transabdominal and transperineal scans and assess all the required parameters on all study participants. Univariate and multivariate analyses were used for selection of potential predictors and model fitting. The independent predictive variables for cesarean delivery included maternal age (odds ratio, 1.12; P=.003), cervical length (odds ratio, 1.08; P=.04), angle of progression at rest (odds ratio, 0.9; P=.001), and occiput posterior position (odds ratio, 5.7; P=.006). We tested the performance of the prediction model on our cross-validation group. The calculated areas under the curve for the ability of the model to predict cesarean delivery were 0.7969 (95% confidence interval, 0.71-0.87) and 0.88 (95% confidence interval, 0.79-0.97) for the developed and validated models, respectively. CONCLUSION: Maternal age and sonographic fetal occiput position, angle of progression at rest, and cervical length before labor induction are very good predictors of induction outcome in nulliparous women at term.

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In 2009, the International Triathlon Union created a new triathlon race format: The World Triathlon Series (WTS), for which only athletes with a top 100 world ranking are eligible. Therefore, the purpose of this study was to analyze the influence of the three disciplines on performance within all the WTS Olympic distance races within two Olympic cycles, and to determine whether their relative contribution changed over the years. Methods: For each of a total of 44 races, final race time and position as well as split times (and positions), and summed time (and position) at each point of the race were collected and included in the analysis. Athletes were divided into 4 groups according to their final race placing (G1: 1st⁻3rd place; G2: 4⁻8th place; G3: 8⁻16th place and G4: ≥17th place). Two-way multivariate ANOVAs were conducted to compare the main effects of years and rank groups. For females, there were significant differences in the swim and bike segment only between G4 and the other groups (p range from 0.001⁻0.029), whilst for the run segment each group differed significantly from each other (p < 0.001). For males, there were significant differences in swim only between G4 and the other groups (p range from 0.001⁻0.039), whilst for the running segment each group differed significantly from the others (p < 0.001). Although we found running to be the segment where there were significant differences between performance groups, it is apparently important for overall success that a good runner be positioned with the first cycling pack. However, bike splits were not different between either of the four male groups or between the first 3 groups of the females. At this very high level of performance, at least in the males, the bike leg seems to be a smooth transition towards running.