AMPD1 polymorphism and response to regadenoson

AIMS: AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. SUBJECTS & METHODS: Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. RESULTS: Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). CONCLUSION: AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects

Generation of human-like motion on anthropomorphic systems using inverse dynamics

This work deals with the generation of human-like whole-body movements on anthropomorphic systems. We propose a general framework to generate robot movements from the definition of ordered stack of tasks and a global resolution scheme that enables to consider different kinds of constraints. We compare qualitatively the robot movements generated from this software with similar recorded human movements. We start with a direct global comparison of body movements. Then we analyze the magnitude of the reconstructed human torques and compare with the simulated robot torques during the motion

Mixed lineage kinase 3 negatively regulates IKK activity and enhances etoposide-induced cell death

AbstractMixed lineage kinase 3 (MLK3) is a mitogen activated protein kinase kinase kinase (MAP3K) that activates multiple MAPK signaling pathways. Nuclear factor kappa B (NF-κB) is a transcription factor that has important functions in inflammation, immunity and cell survival. We found that silencing mlk3 expression with RNA interference (RNAi) in SKOV3 human ovarian cancer epithelial cells and NIH-3T3 murine fibroblasts led to a reduction in the level of the inhibitor of kappa B alpha (IκBα) protein. In addition, we observed enhanced basal IκB kinase (IKK) activity in HEK293 cells transiently transfected with MLK3 siRNA and in NIH3T3 cells stably expressing MLK3 shRNA (shMLK3). Furthermore, the basal level of NF-κB-dependent gene transcription was elevated in shMLK3 cells. Silencing mlk3 expression conferred resistance of cells to etoposide-induced apoptotic cell death and overexpression of wild type MLK3 (MLK3-WT) or kinase-dead MLK3 (MLK3-KD) promoted apoptotic cell death and cleavage of poly (ADP-ribose) polymerase (PARP). Overexpression of MLK3-WT or MLK3-KD enhanced etoposide-induced apoptotic cell death and cleavage of PARP. These data suggest that MLK3 functions to limit IKK activity, and depleting MLK3 helps protect cells from etoposide-induced cell death through activation of IKK-dependent signaling

Climatological variations of total alkalinity and total dissolved inorganic carbon in the Mediterranean Sea surface waters

Abstract. A compilation of data from several cruises between 1998 and 2013 was used to derive polynomial fits that estimate total alkalinity (AT) and total dissolved inorganic carbon (CT) from measurements of salinity and temperature in the Mediterranean Sea surface waters. The optimal equations were chosen based on the 10-fold cross-validation results and revealed that second- and third-order polynomials fit the AT and CT data respectively. The AT surface fit yielded a root mean square error (RMSE) of ± 10.6 μmol kg−1, and salinity and temperature contribute to 96 % of the variability. Furthermore, we present the first annual mean CT parameterization for the Mediterranean Sea surface waters with a RMSE of ± 14.3 μmol kg−1. Excluding the marginal seas of the Adriatic and the Aegean, these equations can be used to estimate AT and CT in case of the lack of measurements. The identified empirical equations were applied on the 0.25° climatologies of temperature and salinity, available from the World Ocean Atlas 2013. The 7-year averages (2005–2012) showed that AT and CT have similar patterns with an increasing eastward gradient. The variability is influenced by the inflow of cold Atlantic waters through the Strait of Gibraltar and by the oligotrophic and thermohaline gradient that characterize the Mediterranean Sea. The summer–winter seasonality was also mapped and showed different patterns for AT and CT. During the winter, the AT and CT concentrations were higher in the western than in the eastern basin. The opposite was observed in the summer where the eastern basin was marked by higher AT and CT concentrations than in winter. The strong evaporation that takes place in this season along with the ultra-oligotrophy of the eastern basin determines the increase of both AT and CT concentrations

Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH)

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017–January 2018), N = 3188 individuals participated [n = 1594 child–caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6–19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children’s well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent–child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: [email protected]). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00127-022-02228-8

The Effectiveness of School-Based Skills-Training Programs Reducing Performance or Social Anxiety: Two Randomized Controlled Trials

Background: Given that high levels of stress during adolescence are associated with negative consequences, it is important that adolescents with psychological needs are supported at an early stage, for instance with interventions at school. However, knowledge about the potential of school-based programs targeting adolescents with psychological needs, aimed at reducing school or social stress, is lacking. Objective: The current study aimed to investigate the effectiveness of two targeted school-based skills-training programs, addressing either skills to deal with performance anxiety or social skills. Methods: Two randomized controlled trials were performed with participants who self-selected to one of the programs. The sample comprised of N = 361 adolescents (Mage = 13.99 years, SD = 0.83) from various educational levels and ethnic identity backgrounds. The performance anxiety program included N = 196 participants (N = 95 in the experimental group), while the social skills program included N = 165 participants (N = 86 in the experimental group). MANCOVA’s were performed. Results: The performance anxiety program had a small effect on reducing adolescents’ test anxiety. Furthermore, for adolescents who attended more than half of the sessions, the program had small effects on reducing test anxiety and fear of failure. The program did not improve adolescents’ coping skills or mental health. The social skills program was not effective in improving social skills, social anxiety, and mental health. Conclusions: A relatively short, targeted program addressing skills to deal with performance anxiety can have the potential to reduce adolescents’ performance anxiety. Trial registration: International Clinical Trials Registry Platform (Netherlands Trial Register, number NTR7680). Registered 12 December 2018. Study protocol van Loon et al., (2019)

CanStem111P trial: A Phase 3 Study of napabucasin (NAPA) plus nab-paclitaxel (nPTX) with gemcitabine (Gem) in adult patients with metastatic pancreatic adenocarcinoma (mPDAC) - Trial in progress

n/

Effect of C-2 substitution on the stability of non-traditional cephalosporins in mouse plasma

This work is licensed under a Creative Commons Attribution 4.0 International License.A systematic study of the stability of a set of cephalosporins in mouse plasma reveals that cephalosporins lacking an acidic moiety at C-2 may be vulnerable to β-lactam cleavage in mouse plasma