Adipose tissue has traditionally been viewed as an energy sink that can store the excess calorie in the form of triglycerides and then release non-esterified fatty acids (NEFA) and glycerol into the blood circulation during lipolysis of triglyceride.
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Arthrogryposis multiplex congenita affects approximately 1 in 3,000 individuals of different ethnic backgrounds and displays an equal incidence in males and females. The underlying mechanism for congenital contracture of the joints is decreased fetal movement during intrauterine development. This disorder is associated with over 400 medical conditions and 350 known genes that display considerable variability in phenotypic expression. In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as the principal diagnostic method of lethal forms of skeletal muscle disorders that present with arthrogryposis and muscle amyoplasia/hypoplasia. Molecular diagnosis provides an opportunity for studying patterns of inheritance and for family counseling concerning future pregnancies.
In the original publication of the article, the first sentence was published incorrectly under the section "Patients and preoperative assessment". The correct sentence should read as, "The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)".
Cav3.1 (α1G) T-type Ca2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular nodal (AVN) cells and contributes to heart rate genesis and AV conduction. However, its role in heart rate (HR) regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear, which is the topic of this study.
L- (ICa-L) and T-type (ICa-T) Ca2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. ICa-T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of ISO were infused through jugular vein and the heart rate was recorded. The EC50 of HR response to isoproterenol was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by isoproterenol was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after isoproterenol; TG SANCs had similar basal beating rates as control SANCs probably due to decreased ICa-L but greater response to isoproterenol than control SANCs. ICa-T in SANCs was significantly increased by isoproterenol.
ICa-T upregulation by β-adrenergic stimulation contributes to HR and conduction regulation by the SAS. TTCC can be a target for slowing heart rates.
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Objectives To describe the implementation of the first phase of a regional perinatal data repository and to provide a roadmap for others to navigate technical, privacy, and data governance concerns in implementing similar resources. Methods Our implementation integrated regional physician billing records with maternal and infant electronic health records from an academic delivery hospital. These records, representing births during 2013–2015, constituted a data core supporting linkage to additional ancillary data sets. Measures obtained from pediatric follow-up, urgent care, emergency, and inpatient encounters were linked at the individual level as were measures obtained by home visitors during pre- and postnatal encounters. Residential addresses were geocoded supporting linkage to area-level measures. Results Integrated data contained regional billing records for 69,290 newborns representing approximately 81% of all regional live births and nearly 95% of live births in the region's most populous county. Billing records linked to 7293 infant delivery hospital records and 7107 corresponding maternal hospital records. Manual review demonstrated 100% validity of matches among audited records. Additionally, 2430 home visiting records were linked to the data core as were pediatric primary care, urgent care, emergency department, and inpatient visits representing 42,541 children. More than 99% of the newborn billing records were geocoded and assigned a census tract identifier. Conclusions for Practice Our approach to methodological and regulatory challenges affords opportunities for expansion of systems to integrate electronic health records originating from additional medical centers as well as individual- and area-level linkage to additional data sets relevant to perinatal health.
In older children, different electroencephalogram-based algorithms for measuring depth of anesthesia displayed a similar performance as in adults, but in infants they have not displayed the same reliability so far. According to the individual developmental state, the Narcotrend distinguishes "differentiated" electroencephalograms, which can be classified using the full Narcotrend Index scale, from "undifferentiated" electroencephalograms, which are classified using a scale with fewer stages.
The objective of this prospective clinical observational study was to assess the feasibility and performance of the Narcotrend monitor in children <2 years within a clinical setting.
Sixty-one children aged 0-24 months undergoing general anesthesia with sevoflurane and remifentanil for elective pediatric surgery were studied. We investigated the percentage of differentiated electroencephalograms and the correlation between multiples of minimal alveolar sevoflurane concentration and the Narcotrend Index according to age groups. Prediction probability was used to evaluate the performance of the Narcotrend Index for differentiation between consciousness and unconsciousness and between different sevoflurane concentrations.
The percentage of differentiated electroencephalograms increased with increasing age (0-3 months: 23.8%, 4-5 months: 87.5%, 6-11 months: 92.3%, 12-24 months: 100%). The overall prediction probability of Narcotrend Index was 1.0 (SE 0.05) for differentiation between awake and loss of consciousness and 1.0 (SE 0.01) for differentiation between anesthetized and return of consciousness. Spearman correlation analysis revealed a significant negative correlation between sevoflurane concentration and the Narcotrend Index (r = −0.78, P < .0001, 95%CI: −0.81 to −0.74). Overall prediction probability of Narcotrend Index to sevoflurane concentration was 0.8 (95%CI: 0.78-0.82).
The Narcotrend monitor indicated a Narcotrend Index in most infants and young children starting from 4 months with significant correlation to and acceptable prediction probability for minimal alveolar sevoflurane concentration.
In the presence of the A-type K+ channel blocker 4-aminopyrdine, spontaneous synchronous network activity develops in the neocortex of mice of either sex. This aberrant synchrony persists in the presence of excitatory amino acid receptor antagonists (EAA blockers), and is thought to arise from synchronous firing of cortical interneurons (INs). Whereas much attention has been given to the mechanisms underlying this GABAergic synchrony, the contribution of specific IN subtypes to the generation of these long-lasting discharges (LLDs) is incompletely understood. We employed genetically-encoded channelrhodopsin and archaerhodopsin opsins to investigate the sufficiency and necessity, respectively, of activation of parvalbumin (PV), somatostatin (SST) and vasointestinal peptide (VIP)-expressing INs for the generation of synchronous neocortical GABAergic discharges. We found light-induced activation of PV or SST INs to be equally sufficient for the generation of LLDs, whereas activation of VIP INs was not. In contrast, light-induced inhibition of PV INs strongly reduced LLD initiation whereas suppression of SST or VIP IN activity only partially attenuated LLD magnitude. These results suggest neocortical INs perform cell type-specific roles in the generation of aberrant GABAergic cortical network activity.
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