The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation.

Most adult hippocampal neural stem cells (NSCs) remain quiescent, with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger the transition from quiescence to activation are still poorly understood. Here, we found the activity of the transcriptional co-activator Yap1 to be enriched in active NSCs. Genetic deletion of Yap1 led to a significant reduction in the relative proportion of active NSCs, supporting a physiological role of Yap1 in regulating the transition from quiescence to activation. Overexpression of wild-type Yap1 in adult NSCs did not induce NSC activation, suggesting tight upstream control mechanisms, but overexpression of a gain-of-function mutant (Yap1-5SA) elicited cell cycle entry in NSCs and hilar astrocytes. Consistent with a role of Yap1 in NSC activation, single cell RNA sequencing revealed a partial induction of an activated NSC gene expression program. Furthermore, Yap1-5SA expression also induced expression of Taz and other key components of the Yap/Taz regulon that were previously identified in glioblastoma stem cell-like cells. Consequently, dysregulated Yap1 activity led to repression of hippocampal neurogenesis, aberrant cell differentiation, and partial acquisition of a glioblastoma stem cell-like signature.

A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function.

Heart diseases are the most common causes of morbidity and death in humans. Using cardiac-specific RNAi-silencing in Drosophila, we knocked down 7061 evolutionarily conserved genes under conditions of stress. We present a first global roadmap of pathways potentially playing conserved roles in the cardiovascular system. One critical pathway identified was the CCR4-Not complex implicated in transcriptional and posttranscriptional regulatory mechanisms. Silencing of CCR4-Not components in adult Drosophila resulted in myofibrillar disarray and dilated cardiomyopathy. Heterozygous not3 knockout mice showed spontaneous impairment of cardiac contractility and increased susceptibility to heart failure. These heart defects were reversed via inhibition of HDACs, suggesting a mechanistic link to epigenetic chromatin remodeling. In humans, we show that a common NOT3 SNP correlates with altered cardiac QT intervals, a known cause of potentially lethal ventricular tachyarrhythmias. Thus, our functional genome-wide screen in Drosophila can identify candidates that directly translate into conserved mammalian genes involved in heart function.

How Would I Treat My Own Thoracoabdominal Aortic Aneurysm: Perioperative Considerations From the Anesthesiologist Perspective.

A thoracoabdominal aortic aneurysm (TAAA) can be potentially life-threatening due to its associated risk of rupture. Thoracoabdominal aortic aneurysm repair, performed as endovascular repair and/or open surgery, is the recommended therapy of choice. Hemodynamic instability, severe blood loss, and spinal cord or cerebral ischemia are some potential hazards the perioperative team has to face during these procedures. Therefore, preoperative risk assessment and intraoperative anesthesia management addressing these potential hazards are essential to improving patients' outcomes. Based on a presented index case, an overview focusing on anesthetic measures to identify perioperatively and manage these risks in TAAA repair is provided.

Do Adolescents Adopt the Prosocial Behaviors of the Classmates They Like? A Social Network Analysis on Prosocial Contagion.

While the influence of high-status peers on maladaptive behaviors is well-documented, socialization processes of prosocial behavior through high-status peers remain understudied. This study examined whether adolescents' prosocial behavior was influenced by the prosocial behavior of the peers they liked and whether this effect was stronger when the peers they liked were also well-liked by their classmates. Three waves of data, six months apart, were collected among Chilean early adolescents who completed peer nominations and ratings at Time 1 (n = 294, Mage = 13.29, SD = 0.62; 55.1% male), Time 2 (n = 282), and Time 3 (n = 275). Longitudinal social network analyses showed that adolescents adopted the prosocial behavior of the classmates they liked - especially if these classmates were well-liked by peers in general. In addition, adolescents low in likeability were more susceptible to this influence than adolescents high in likeability. The influence resulted both in increases and - especially - decreases in prosocial behavior, depending on the level of prosociality of the liked peer. Findings suggest that likeability represents an important aspect of peer status that may be crucial for understanding the significance of peer influence with respect to prosocial behaviors during adolescence. Pre-Registration: https://osf.io/u4pxm .

Magnetic Resonance Imaging or Computed Tomography for Suspected Acute Stroke: Association of Admission Image Modality with Acute Recanalization Therapies, Workflow Metrics, and Outcomes.

OBJECTIVE: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door-to-needle (DTN) time, door-to-puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT). METHODS: An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss-Stroke-Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed-effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0-2) at 90 days. RESULTS: Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0-6] vs 4 [1-11]), and presented later after symptom onset (150 vs 123 min, p < 0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73-0.96), but not with MT (aOR 1.11, 0.93-1.34); longer adjusted DTN (+22 min [13-30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30-1.81). INTERPRETATION: We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue-based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184-194.

Dexmedetomidine Sedation Combined With Remifentanil in MitraClip Procedures is Feasible and Improves Hemodynamics.

OBJECTIVES: The objective of the study was to compare the overall feasibility, respiratory and hemodynamic stability, as well as process times of a dexmedetomidine-based sedative regimen compared with general anesthesia among patients undergoing MitraClip procedures. DESIGN: A retrospective cohort study. SETTING: A single tertiary care university center. PARTICIPANTS: The study included 79 patients. INTERVENTIONS: Dexmedetomidine sedation versus general anesthesia. MEASUREMENTS AND MAIN RESULTS: Seventy-nine MitraClip procedures in dexmedetomidine/remifentanil conscious sedation (DCS, n = 26) or general anesthesia (GA, n = 53), performed between 2018 and 2020 at Charité - Universitätsmedizin Berlin, were analyzed retrospectively. Patients' median age was 81 years in both groups without differences in preinterventional EuroScore I (DCS 6 [5; 8], GA 7 [6; 8]) or systolic function (left ventricular ejection fraction: DCS 50% [32; 60] v. GA 50% [36; 60]; tricuspid annular plane systolic excursion: DCS 19 mm [16; 22] v GA 19 mm [15; 22]). During MitraClip procedures, respiratory parameters revealed no differences between groups, whereas patients under DCS showed higher mean arterial pressures (DCS 64 mmHg [59; 74] v GA 58 mmHg [53; 66]) and needed less norepinephrine (DCS 0.0µg/kg/min [0.0; 0.2] v GA 0.08 µg/kg/min [0.05; 0.15]). Emergence from both anesthesia regimens to readiness for intensive care unit transfer was faster in DCS (8 min [4; 18] v GA 16 min [11; 23]); however, total process time was comparable between groups (DCS 128 min [104; 155] v GA 142 min [117; 190]). Two patients required a switch from DCS to GA due to oral bleeding or prolonged procedure time. Both were excluded from the analysis. There was no switch to open surgery and no differences in postoperative complications between DCS and GA. CONCLUSION: Dexmedetomidine/remifentanil sedation appears to be feasible and a safe option for MitraClip procedures, and provides better hemodynamic stability with faster emergence times compared with general anesthesia.

A comprehensive echocardiographic analysis during simulated hypovolaemia: An observational study.

BACKGROUND: Peri-operative and critically ill patients often experience mild to moderate hypovolaemic shock with preserved mean arterial pressure (MAP), heart rate (HR) and decreased stroke volume index (SVI). OBJECTIVES: The aim of this study was to evaluate echocardiographic parameters during simulated mild to moderate central hypovolaemia. DESIGN: This was a prospective preclinical study. SETTING: Laboratory trial performed in Charité-Universitätsmedizin Berlin, Germany. PATIENTS AND METHODS: Thirty healthy male volunteers underwent graded central hypovolaemia using a lower body negative pressure (LBNP) chamber with a stepwise decrease to simulate a mild (-15 mmHg), mild-to-moderate (-30 mmHg), and moderate state of hypovolaemic shock (-45 mmHg). During every stage, a transthoracic echocardiography examination (TTE) was performed by a certified examiner. MAIN OUTCOME MEASURES: Systolic and diastolic myocardial performance markers, as well as cardiac volumes were recorded during simulated hypovolaemia and compared to baseline values. RESULTS: During simulated hypovolaemia via LBNP, SVI decreased progressively at all stages, whereas MAP and HR did not consistently change. Left ventricular (LV) ejection fraction decreased at -30 and -45 mmHg. Simultaneously with SVI decline, LV global longitudinal strain (LV GLS), tricuspid annular plain systolic excursion (TAPSE), and right ventricular RV S' and left-atrial end-systolic volume (LA ESV) decreased compared to baseline at all stages. CONCLUSIONS: In this study, simulated central hypovolaemia using LBNP did not induce consistent changes in MAP and HR. SVI decreased and was associated with deteriorated right- and left-ventricular function, observed with echocardiography. The decreased filling status was characterised by decreased LA ESV. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT03481855.

Intraoperative Beat-to-Beat Pulse Transit Time (PTT) Monitoring via Non-Invasive Piezoelectric/Piezocapacitive Peripheral Sensors Can Predict Changes in Invasively Acquired Blood Pressure in High-Risk Surgical Patients.

BACKGROUND: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. METHODS: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson's correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). RESULTS: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). CONCLUSIONS: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis.

BACKGROUND: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. METHODS: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. RESULTS: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). CONCLUSIONS: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Association of the COVID-19 outbreak with acute stroke care in Switzerland.

BACKGROUND AND PURPOSE: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. METHODS: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. RESULTS: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). CONCLUSIONS: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained.

Isolated Ruptured Paravisceral Penetrating Aortic Ulcers.

BACKGROUND: The goal of this study is to investigate the clinical presentation, treatment options, and outcomes of the patients with isolated ruptured paravisceral penetrating aortic ulcers (PV-PAU). METHODS: All patients presenting with acute aortic syndrome from 2015 to 2020 were screened, of which patients with isolated ruptured PV-PAU were included in this retrospective study. Study endpoints were the assessment of treatment options, technical success, and clinical outcome. Outcome measures included major perioperative complications and mortality. RESULTS: Sixteen patients (11 men; median age 68; IQR 60 - 75 years) presented with isolated ruptured PV-PAU were included in this study. The median follow-up was 25 months (range 1 - 51). Ruptured PV-PAUs represented 12.3% of the ruptured aortic aneurysms in all locations. PV-PAUs were found in segment A (n = 8, 50%), segment B (n = 5, 31%), and segment C (n = 3, 19%). PV-PAUs showed a mean protrusion distance of 27±10 mm, a mean neck diameter of 21 ± 7 mm, and maximal aortic diameter of 50 ± 11 mm. Five patients (31%) showed hemodynamic instability on admission and needed intense fluid resuscitation. Of those, 2 patients needed urgent laparotomy with a fast transabdominal supraceliac aortic clamping, one needed an aortic balloon occlusion to obtain rapid aortic control. The open aortic repair was the most frequently performed surgery (11/16, 69%), followed by hybrid procedures (3/16) and parallel graft chimney technique (2/16). Two patients died during the follow-up, calculating for in-hospital and 1-year mortality rates of 6 - 12%, respectively. The postoperative morbidity rate was 31%. Postoperative complications included acute renal failure (31%), pneumonia (25%), and 1case of ischemic colitis (6%). No spinal cord ischemia was reported. CONCLUSIONS: Ruptured PV-PAU is a rare and challenging diagnostic and therapeutic entity. Open aortic repair seems to be a reliable option in treating patients with isolated ruptured PV-PAUs. Hybrid procedures and parallel stent-graft techniques can only be used in selected patients.

Bidirectional Associations of Prosocial Behavior with Peer Acceptance and Rejection in Adolescence.

As most studies on the link between peer status and prosocial behavior are cross-sectional, conducted with children, and operationalize status as the difference between acceptance and rejection, it remains unclear whether peer acceptance and rejection are consequences or prerequisites of prosocial behavior in adolescence. To fill this gap, this study examines the bidirectional associations of prosocial behavior with peer acceptance and peer rejection with data collected at 3 time points, 6 months apart, in a sample of 660 early Chilean adolescents (M = 12.94, SD = 0.62; 55.1% boys). Cross-lagged panel analyses showed that prosocial behavior positively predicted future peer acceptance, whereas peer acceptance had no significant effect on future prosocial behavior. The association between rejection and prosocial behavior was negative and bidirectional between Time 1 and Time 2. When a new academic year began, between Time 2 and Time 3, prosocial behavior negatively predicted rejection, whereas rejection in the previous grade level was positively associated with prosocial behavior at the beginning of the next grade. Multi-group panel analyses did not detect significant differences between boys and girls in the cross-lagged associations of prosociality with peer acceptance and peer rejection. The results suggest that acting prosocially can make adolescents better liked by their peers and highlight the possible importance of the transition to a new academic year for the prosocial behavior of previously rejected students. Implications for future research on peer relations are discussed.

Preoperative and ICU Scoring Models for Predicting the In-Hospital Mortality of Patients With Ruptured Abdominal Aortic Aneurysms.

OBJECTIVES: This study's objective was to compare several preoperative and intensive care unit (ICU) prognostic scoring systems for predicting the in-hospital mortality of ruptured abdominal aortic aneurysms (RAAAs). DESIGN: Retrospective cohort study. SETTING: Single tertiary university center. PARTICIPANTS: The study comprised 157 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 157 patients (82% male) presented with RAAA at Charité University Hospital from January 2011 to December 2020. The mean age was 74 years (standard deviation ten years). In-hospital mortality was 29% (n = 45), of whom nine patients (6%) died en route to the operating room, 13 (8%) on the operating table, and 23 (15%) in the ICU. A total of 135 patients (86%) were admitted to the ICU. All six models demonstrated good discriminating performance between survivors and nonsurvivors. Overall, the area under the curve (AUC) for RAAA preoperative scores was greater than those for ICU scores. The largest AUC was achieved with the Vascular Study Group of New England (VSGNE) RAAA risk score (AUC = 0.87 for all patients, AUC = 0.84 for patients admitted to the ICU), followed by Hardman Index (AUC = 0.83 for all patients, AUC = 0.81 for patients admitted to the ICU), and Glasgow Aneurysm Score (AUC = 0.74 for all patients, AUC = 0.83 for patients admitted to the ICU). The largest AUC for ICU scores (only patients admitted to the ICU) was achieved with Simplified Acute Physiology Score II (0.75), followed by Sepsis-related Organ Failure Assessment (0.73), and Acute Physiology and Chronic Health Evaluation II (0.71). CONCLUSIONS: Preoperative and ICU scores can predict the mortality of patients presenting with RAAA. In addition, the discriminatory ability of preoperative scores between survivors and nonsurvivors was larger than that for ICU scores.

The role of perspective-taking and low social class prejudice on cross-ethnic friendship formation.

Cross-ethnic friendships offer a unique opportunity for improving intergroup relations and reduce prejudice, yet ethnic segregation of friendship networks is often seen as a major obstacle to the integration of immigrant students in educational contexts. This article examines the role of perspective-taking abilities and prejudice towards low social class peers on the probability of cross-ethnic friendships in a sample of 242 students from five multicultural classrooms in Chile (Mage = 12.3; SD = 0.69, 45% girls). It was expected that students who reported high levels of perspective-taking abilities and low levels of prejudice towards low social class peers were more likely to form and maintain cross-ethnic friendships. Longitudinal network analysis (RSiena) was used to examine these hypotheses, confirming the role of both variables in fostering (and reducing) friendships among Chilean and immigrant adolescents. Results are discussed in light of an intersectional framework between social class and ethnicity. Implications for social-emotional interventions in multicultural educational contexts are also discussed.

Temperature-responsive miRNAs in Drosophila orchestrate adaptation to different ambient temperatures.

The majority of Drosophila genes are expressed in a temperature-dependent manner, but the way in which small RNAs may contribute to this effect is completely unknown as we currently lack an idea of how small RNA transcriptomes change as a function of temperature. Applying high-throughput sequencing techniques complemented by quantitative real-time PCR experiments, we demonstrate that altered ambient temperature induces drastic but reversible changes in sequence composition and total abundance of both miRNA and piRNA populations. Further, mRNA sequencing reveals that the expression of miRNAs and their predicted target transcripts correlates inversely, suggesting that temperature-responsive miRNAs drive adaptation to different ambient temperatures on the transcriptome level. Finally, we demonstrate that shifts in temperature affect both primary and secondary piRNA pools, and the observed aberrations are consistent with altered expression levels of the involved Piwi-pathway factors. We further reason that enhanced ping-pong processing at 29°C is driven by dissolved RNA secondary structures at higher temperatures, uncovering target sites that are not accessible at low temperatures. Together, our results show that small RNAs are an important part of epigenetic regulatory mechanisms that ensure homeostasis and adaptation under fluctuating environmental conditions.

Adolescents' Friendships, Academic Achievement, and Risk Behaviors: Same-Behavior and Cross-Behavior Selection and Influence Processes.

This study examined to what extent adolescents' and their friends' risk behaviors (i.e., delinquency and alcohol use) hinder or promote their academic achievement (grade point average [GPA]), and vice versa. Longitudinal data were used (N = 1,219 seventh- to ninth-grade adolescents; Mage  = 13.69). Results showed that risk behaviors negatively affected adolescents' GPA, whereas GPA protected against engaging in risk behaviors. Moreover, adolescents tended to select friends who have similar behaviors and friends' behaviors became more similar over time (same-behavior selection and influence). Furthermore, although same-behavior effects seemed to dominate, evidence was found for some cross-behavior selection effects and a tendency in seventh grade for cross-behavior influence effects. Concluding, it is important to investigate the interplay between different behaviors with longitudinal social network analysis.

Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila.

During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.

Combination of problem-based learning with high-fidelity simulation in CPR training improves short and long-term CPR skills: a randomised single blinded trial.

BACKGROUND: Performance of sufficient cardiopulmonary resuscitation (CPR) by medical personnel is critical to improve outcomes during cardiac arrest. It has however been shown that even health care professionals possess a lack of knowledge and skills in CPR performance. The optimal method for teaching CPR remains unclear, and data that compares traditional CPR instructional methods with newer modalities of CPR instruction are needed. We therefore conducted a single blinded, randomised study involving medical students in order to evaluate the short- and long-term effects of a classical CPR education compared with a bilateral approach to CPR training, consisting of problem-based learning (PBL) plus high fidelity simulation. METHODS: One hundred twelve medical students were randomized during a curricular anaesthesiology course to a control (n = 54) and an intervention (n = 58) group. All participants were blinded to group assignment and partook in a 30-min-lecture on CPR basics. Subsequently, the control group participated in a 90-min tutor-guided CPR hands-on-training. The intervention group took part in a 45-min theoretical PBL module followed by 45 min of high fidelity simulated CPR training. The rate of participants recognizing clinical cardiac arrest followed by sufficiently performed CPR was the primary outcome parameter of this study. CPR performance was evaluated after the intervention. In addition, a follow-up evaluation was conducted after 6 months. RESULTS: 51.9% of the intervention group met the criteria of sufficiently performed CPR as compared to only 12.5% in the control group on the day of the intervention (p = 0.007). Hands-off-time as a marker for CPR continuity was significantly less in the intervention group (24.0%) as compared to the control group (28.3%, p = 0.007, Hedges' g = 1.55). At the six-month follow-up, hands-off-time was still significantly lower in the intervention group (23.7% vs. control group: 31.0%, p = 0.006, Hedges' g = 1.88) but no significant difference in sufficiently performed CPR was detected (intervention group: 71.4% vs. control group: 54.5%, p = 0.55). CONCLUSION: PBL combined with high fidelity simulation training leads to a measurable short-term increase in initiating sufficient CPR by medical students immediately after training as compared to classical education. At six month post instruction, these differences remained only partially.

The Interplay of Adolescents' Aggression and Victimization with Friendship and Antipathy Networks within an Educational Prosocial Intervention.

How the interplay between peer relationships and behaviors unfolds and how this differs between classrooms is an understudied topic. This study examined whether adolescents befriend or dislike peers whom they consider as aggressor or victim and whether these results differ in classrooms that received an intervention to promote prosocial behavior compared to classrooms without the intervention. The sample was composed of 659 seventh graders (Mage = 12.32; 48% girls) from nine intervention and seven control classrooms in eight schools in Santiago, Chile. It was hypothesized that adolescents in intervention classrooms would be less befriended and more disliked by classmates who considered them as aggressors, and more befriended and less disliked by classmates who considered them as victims, compared to control classrooms. Longitudinal multiplex social network analyses (RSiena) indicate that antipathies toward peers considered as aggressive and victimized were significantly lower in intervention classrooms than in control classrooms, but no significant differences were found for friendships. These findings suggest that the impact of an educational intervention may go beyond changing individual behavior and extend to the way peer relations develop in classrooms.