Lehmanlausten8638

Objective The aim of this study is to examine factors associated with early neonatal (death within first 7 days of birth) and infant (death during the first year of life) mortality among infants born with myelomeningocele. Study design We examined linked data from the California Perinatal Quality Care Collaborative, vital records, and hospital discharge records for infants born with myelomeningocele from 2006 to 2011. Survival probability was calculated using Kaplan-Meier Product Limit method and 95% confidence intervals (CI) using Greenwood's method; Cox proportional hazard models were used to estimate unadjusted and adjusted hazard ratios (HR) and 95% CI. click here Results Early neonatal and first-year survival probabilities among infants born with myelomeningocele were 96.0% (95% CI 94.1-97.3%) and 94.5% (95% CI 92.4-96.1%), respectively. Low birthweight and having multiple co-occurring birth defects were associated with increased HRs ranging between 5 and 20, while having congenital hydrocephalus and receiving hospital transfer from the birth hospital to another hospital for myelomeningocele surgery were associated with HRs indicating a protective association with early neonatal and infant mortality. Conclusion Maternal race/ethnicity and social disadvantage did not predict early neonatal and infant mortality among infants with myelomeningocele; presence of congenital hydrocephalus and the role of hospital transfer for myelomeningocele repair should be further examined. Key points · Mortality in myelomeningocele is a concern. · Social disadvantage was not associated with death. · Hospital-based factors should be further examined.Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain's MOR availability was measured with positron emission tomography (PET) using an agonist radioligand [11C]carfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.Previous research has implicated the serotonin-2B (5-HT2B) receptor as a possible contributor to the antidepressant-like response. Aripiprazole has been successfully used in combination with selective serotonin reuptake inhibitors (SSRIs) in treatment-resistant depression and it, among all receptors, exhibits the highest affinity for the 5-HT2B receptor. However, the potential contribution of such an antagonistic action on 5-HT2B receptors in the context of adjunct therapy is not known. In vivo electrophysiological recordings of ventral tegmental area (VTA) dopamine (DA) neurons, dorsal raphe nucleus (DRN) 5-HT neurons and pyramidal neurons in the medial prefrontal cortex (mPFC), and the hippocampus were conducted in anaesthetized Sprague-Dawley rats after the administration of 5-HT2B receptor ligands alone or in combination with the SSRI escitalopram. An escitalopram-induced decrease in DA, but not 5-HT firing activity, was rescued by 2-day co-administration of the selective 5-HT2B receptor antagonist LY266097. In the mPFC, 14-day escitalopram administration alone had no effect on pyramidal neuron firing and burst activity, whereas, aripiprazole administered alone or in combination with escitalopram for 14 days increased pyramidal neuron firing and burst activity. Likewise, the administration of LY266097 alone or its addition on the last 3 days of a 14-day escitalopram regimen increased pyramidal neuron firing and burst activity. These results indicated that 5-HT2B receptors play, at least in part, a role in this enhancement. In the hippocampus, 5-HT2B receptor activation by BW723c86 decreased escitalopram-induced inhibition of 5-HT reuptake, which was reversed by a 5-HT2B receptor antagonist. Altogether, these results put into evidence the possibility that 5-HT2B receptor blockade contributes to the therapeutic effect of aripiprazole addition to SSRIs in depression.Functional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects. Our main analysis showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. In our exploratory analysis, we found that MPH-induced regional variations in the DAT and NET-enriched FC maps were significantly correlated with some of the inter-individual differences on key behavioural responses associated with the reinforcement-learning task. Our findings show that main MPH-related FC changes at rest can be understood through the distribution of DAT in the brain. Furthermore, they suggest that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to engagement of distinct molecular targets.Objectives To investigate whether tethered swimming (TS) performed 8 minutes before a 50-m freestyle swimming sprint could be an effective postactivation potentiation method to improve performance in young swimmers. Methods Fourteen regional-level male adolescent swimmers (age 13.0 [2.0] y; height 161.1 [12.4] cm; body mass 52.5 [9.5] kg) underwent 2 trial conditions in a randomized and counterbalanced order (1 experimental [TS], 1 control) on different days. During the experimental session, the participants performed a standard warm-up of 1200 m followed by a TS exercise, which consisted of 3 × 10-second maximal efforts of TS with 1-minute rests between bouts. In the control condition, the warm-up phase was immediately followed by 200 m at a moderate pace (same duration as the TS in the experimental session). Performance (time trial); biomechanical (stroke length), physiological (blood lactate concentrations), and psychophysiological (ratings of perceived exertion) variables; and countermovement-jump (CMJ) flight time were collected. Results TS warm-up had no significant effect on 50-m swimming performance (P = .27), postexercise ratings of perceived exertion, stroke length, or CMJ flight time (P ≥ .05). Blood lactate concentrations significantly increased at the end of the warm-up in the TS condition only (interaction effect F1.91,29.91 = 4.91, P = .01, η2 = .27) and after the 50-m trial in both conditions (F1.57,20.41 = 62.39, P = .001, η2 = .82). Conclusions The present study demonstrated that 3 × 10-second TS exercises performed 8 minutes prior to the event did not affect ratings of perceived exertion, stroke length, or CMJ flight time. In addition, tethered swimming did not affect 50-m freestyle sprint performance in young swimmers.Purpose To analyze the acute and short-term physical and metabolic responses to resisted sprint training with 5 different loading conditions (0%, 20%, 40%, 60%, and 80% body mass). Methods Fifteen male participants performed 8 × 20-m sprints with 2-minute rests between sprints with 5 different loading conditions. Subjects performed a battery of tests (creatine kinase and lactate concentrations, countermovement jump, 20-m sprint, and isokinetic knee extension and flexion contractions) at 3 different time points (preexercise [PRE], postexercise [POST], and 24-h postexercise [POST24H]). Results Results revealed significant increases in blood lactate for all loading conditions; however, as sled loadings increased, higher blood lactate concentrations and increments in sprint times during the training session were observed. Significant increases in creatine kinase concentration were observed from PRE to POST24H for all loading conditions. Concerning physical performance, significant decreases in countermovement-jump height from PRE to POST were found for all loading conditions. In addition, significant decreases in 20-m sprint performance from PRE to POST were observed for 0% (P = .05) and 80% (P = .02). No significant differences with PRE were observed for the physical-performance variables at POST24H, except for 20% load, which induced a significant decrease in mean power during knee flexion (P = .03). Conclusions These results suggest that the higher the load used during resisted sprint training, the higher the physical-performance impairments and metabolic response produced, although all loading conditions led to a complete recovery of sprint performance at POST24H.