Brugada Syndrome and Kawasaki Disease in a Two-Year-Old: A Case of Double Jeopardy.

Brugada syndrome (BrS) is a genetic channelopathy that may predispose to ventricular arrhythmia. It is inherited as an autosomal dominant pattern with incomplete penetrance. Fever can unmask Brugada syndrome in children who have a genetic predisposition.

RORc expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions.

Background And Aims: RORc-expressing immune cells play important roles in inflammation, autoimmune disease and cancer. They are required for lymphoid organogenesis and have been implicated in tertiary lymphoid structure (TLS) formation. TLSs are formed in many cancer types and have been correlated with better prognosis and response to immunotherapy.

Protein-free media for cardiac differentiation of hPSCs in 2000 mL suspension culture.

Background: Commonly used media for the differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CMs) contain high concentrations of proteins, in particular albumin, which is prone to quality variations and presents a substantial cost factor, hampering the clinical translation of in vitro-generated cardiomyocytes for heart repair. To overcome these limitations, we have developed chemically defined, entirely protein-free media based on RPMI, supplemented with L-ascorbic acid 2-phosphate (AA-2P) and either the non-ionic surfactant Pluronic F-68 or a specific polyvinyl alcohol (PVA).

Methods And Results: Both media compositions enable the efficient, directed differentiation of embryonic and induced hPSCs, matching the cell yields and cardiomyocyte purity ranging from 85 to 99% achieved with the widely used protein-based CDM3 medium.

A Possible Role of Tetrodotoxin-Sensitive Na Channels for Oxidation-Induced Late Na Currents in Cardiomyocytes.

An accumulation of reactive oxygen species (ROS) in cardiomyocytes can induce pro-arrhythmogenic late Na currents by removing the inactivation of voltage-gated Na channels including the tetrodotoxin (TTX)-resistant cardiac α-subunit Nav1.5 as well as TTX-sensitive α-subunits like Nav1.2 and Nav1.

Rapid sequential clustering of NMDARs, CaMKII, and AMPARs upon activation of NMDARs at developing synapses.

Rapid, synapse-specific neurotransmission requires the precise alignment of presynaptic neurotransmitter release and postsynaptic receptors. How postsynaptic glutamate receptor accumulation is induced during maturation is not well understood. We find that in cultures of dissociated hippocampal neurons at 11 days (DIV) numerous synaptic contacts already exhibit pronounced accumulations of the pre- and postsynaptic markers synaptotagmin, synaptophysin, synapsin, bassoon, VGluT1, PSD-95, and Shank.

Extensive elimination of acinar cells during normal postnatal pancreas growth.

While programmed cell death plays important roles during morphogenetic stages of development, post-differentiation organ growth is considered an efficient process whereby cell proliferation increases cell number. Here we demonstrate that early postnatal growth of the pancreas unexpectedly involves massive acinar cell elimination. Measurements of cell proliferation and death in the human pancreas in comparison to the actual increase in cell number predict daily elimination of 0.

MAP3D: An explorative approach for automatic mapping of real-world eye-tracking data on a virtual 3D model.

Mobile eye tracking helps to investigate real-world settings, in which participants can move freely. This enhances the studies' ecological validity but poses challenges for the analysis. Often, the 3D stimulus is reduced to a 2D image (reference view) and the fixations are manually mapped to this 2D image.

Selectively Tuning the Substrate Adhesion Strength of Aligned Carbon Nanotube Arrays via Thermal Postgrowth Processing.

The excellent intrinsic properties of aligned nanofibers, such as carbon nanotubes (CNTs), and their ability to be easily formed into multifunctional 3D architectures motivate their use for a variety of commercial applications, such as batteries, chemical sensors for environmental monitoring, and energy harvesting devices. While controlling nanofiber adhesion to the growth substrate is essential for bulk-scale manufacturing and device performance, experimental approaches and models to date have not addressed tuning the CNT array-substrate adhesion strength with thermal processing conditions. In this work, facile "one-pot" thermal postgrowth processing (at temperatures = 700-950 °C) is used to study CNT-substrate pull-off strength for millimeter-tall aligned CNT arrays.

Investigating visual expertise in sculpture: A methodological approach using eye tracking.

Research on visual expertise has progressed significantly due to the availability of eye tracking tools. However, attempts to bring together research on expertise and eye tracking methodology provoke several challenges, because visual information processes should be studied in authentic and domain-specific environments. Among the barriers to designing appropriate research are the proper definition of levels of expertise, the tension between internal (experimental control) and external (authentic environments) validity, and the appropriate methodology to study eye movements in a three-dimensional environment.

Erratum to 'Total Hip Arthroplasty for Ankylosis Requiring Rotational Rectus Femoris Flap and Skin Graft for Wound Closure' [Arthroplasty Today 6 (2020) 141-145].

[This corrects the article DOI: 10.1016/j.artd.

Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia.

Schizophrenia is a psychiatric disorder that affects over 20 million people globally. Notably, schizophrenia is associated with decreased density of dendritic spines and decreased levels of d-serine, a co-agonist required for opening of the N-methyl-d-aspartate receptor (NMDAR). We hypothesized that lowered d-serine levels associated with schizophrenia would enhance ion flux-independent signaling by the NMDAR, driving destabilization and loss of dendritic spines.

Ion flux-independent NMDA receptor signaling.

NMDA receptors play vital roles in a broad array of essential brain functions, from synaptic transmission and plasticity to learning and memory. Historically, the fundamental roles of NMDARs were attributed to their specialized properties of ion flux. More recently, it has become clear that NMDARs also signal in an ion flux-independent manner.

The alcohol industry's involvement with road safety NGOs.

Background: Road crashes are a major cause of death among all age groups and the leading cause of death among persons 5-29 years, according to the World Health Organization. One key risk factor is drink-driving. While the world's leading beer, wine, and spirit producers have pledged to combat drink-driving, there is increasing evidence showing the alcohol industry's promotion of solutions which minimally impact sales.

miRNA-Guided Imaging and Photodynamic Therapy Treatment of Cancer Cells Using Zn(II)-Protoporphyrin IX-Loaded Metal-Organic Framework Nanoparticles.

An analytical platform for the selective miRNA-21-guided imaging of breast cancer cells and miRNA-221-guided imaging of ovarian cancer cells and the selective photodynamic therapy (PDT) of these cancer cells is introduced. The method is based on Zn(II)-protoporphyrin IX, Zn(II)-PPIX-loaded UiO-66 metal-organic framework nanoparticles, NMOFs, gated by two hairpins H/H through ligation of their phosphate residues to the vacant Zr-ions associated with the NMOFs. The hairpins are engineered to include the miRNA recognition sequence in the stem domain of H, and in the H and H, partial locked stem regions of G-quadruplex subunits.

Secondary Traumatic Stress and Vigor Among Neonatal Intensive Care Unit Personnel: The Moderator Role of Coping Flexibility.

Background: The demanding and highly stressful work environment of the neonatal intensive care unit (NICU) has led to the identification of a possible psychological stress reaction among NICU nurses and physicians, termed secondary traumatic stress (STS).

Purpose: The current study aimed to explore the association between vigor at work (as an energy resource) and STS, while considering their association with the professional role (nurses/physicians-as a condition resource) as well as with coping flexibility (as a personal resource).

Methods: In this cross-sectional study physicians and nurses working in NICUs across Israel completed a questionnaire comprising sections on demographics and professional characteristics, self-rated health, STS, coping flexibility, and vigor.

Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning.

Dynamic control of protein degradation via the ubiquitin proteasome system (UPS) is thought to play a crucial role in neuronal function and synaptic plasticity. The proteasome subunit Rpt6, an AAA ATPase subunit of the 19S regulatory particle (RP), has emerged as an important site for regulation of 26S proteasome function in neurons. Phosphorylation of Rpt6 on serine 120 (S120) can stimulate the catalytic rate of substrate degradation by the 26S proteasome and this site is targeted by the plasticity-related kinase Ca/calmodulin-dependent kinase II (CaMKII), making it an attractive candidate for regulation of proteasome function in neurons.

Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines.

Experience-dependent refinement of neuronal connections is critically important for brain development and learning. Here, we show that ion-flow-independent NMDA receptor (NMDAR) signaling is required for the long-term dendritic spine growth that is a vital component of brain circuit plasticity. We find that inhibition of p38 mitogen-activated protein kinase (p38 MAPK), which is downstream of non-ionotropic NMDAR signaling in long-term depression (LTD) and spine shrinkage, blocks long-term potentiation (LTP)-induced spine growth but not LTP.

Substrate adhesion evolves non-monotonically with processing time in millimeter-scale aligned carbon nanotube arrays.

The advantageous intrinsic and scale-dependent properties of aligned nanofibers (NFs) and their assembly into 3D architectures motivate their use as dry adhesives and shape-engineerable materials. While controlling NF-substrate adhesion is critical for scaled manufacturing and application-specific performance, current understanding of how this property evolves with processing conditions is limited. In this report, we introduce substrate adhesion predictive capabilities by using an exemplary array of NFs, aligned carbon nanotubes (CNTs), studied as a function of their processing.

Total Hip Arthroplasty for Ankylosis Requiring Rotational Rectus Femoris Flap and Skin Graft for Wound Closure.

We present a case report of a 51-year-old Ghanaian immigrant who underwent total hip arthroplasty in the setting of spontaneous ankylosis of unknown etiology. The increase in offset of the patient's limb through reconstruction, in combination with severe soft-tissue atrophy of the lower extremity, resulted in a soft-tissue defect that could not be closed primarily. This ultimately required a rectus femoris rotational flap and skin grafting for coverage.

Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling in Dendritic Spine Shrinkage.

Structural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength.

UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma.

Although clonal neo-antigen burden is associated with improved response to immune therapy, the functional basis for this remains unclear. Here we study this question in a novel controlled mouse melanoma model that enables us to explore the effects of intra-tumor heterogeneity (ITH) on tumor aggressiveness and immunity independent of tumor mutational burden. Induction of UVB-derived mutations yields highly aggressive tumors with decreased anti-tumor activity.

Aligned carbon nanotube morphogenesis predicts physical properties of their polymer nanocomposites.

Carbon nanostructure (CNS) based polymer nanocomposites (PNCs) are of interest due to the superior properties of the CNS themselves, scale effects, and the ability to transfer these properties anisotropically to the bulk material. However, measurements of physical properties of such materials are not in agreement with theoretical predictions. Recently, the ability to characterize the 3D morphology of such PNCs at the nanoscale has been significantly improved, with rich, quantitative data extracted from tomographic transmission electron microscopy (TEM).

Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2.

Reprogrammed glucose metabolism of enhanced aerobic glycolysis (or the Warburg effect) is known as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer metabolism at the level of both glycolysis and gluconeogenesis are mostly unknown. We previously showed that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a proto-oncogene in hepatocellular carcinoma (HCC).

microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.

Background & Aims: We performed an integrated analysis to identify microRNAs (miRNAs) and messenger RNAs (mRNAs) with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.

Methods: We analyzed miRNA and mRNA expression profiles of liver tissues from mice with diethylnitrosamine-induced hepatocarcinogenesis, conditional expression of lymphotoxin alpha and lymphotoxin beta, or inducible expression of a Myc transgene (Tet-O-Myc mice), as well as male C57BL/6 mice (controls). miRNA mimics were expressed and miRNAs and mRNAs were knocked down in human (Huh7, Hep3B, JHH2) hepatoma cell lines; cells were analyzed for viability, proliferation, apoptosis, migration, and invasion.