Brain damage caused by neonatal hypoxia-ischemia and the effects of hypothermia in severe combined immunodeficient (SCID) mice.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of brain damage in newborns. Although therapeutic hypothermia has been shown to be neuroprotective against neonatal HIE in clinical trials, its effect is not satisfactory. Cell-based therapies have attracted much attention as novel treatments for HIE.

Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains.

Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 10 cells after 48 h.

Allergen immunotherapy in atopic dermatitis: Light and shadow in children.

Atopic dermatitis (AD) is a chronic remitting-relapsing inflammatory skin disorder. Due to the multifactorial pathogenesis, there are numerous therapeutic management approaches, mainly based on symptomatic treatments. In recent years, allergen immunotherapy (AIT) has been progressively advanced as targeted disease-modifying treatment of allergic disease.

Blastomere removal affects homeostatic control leading to obesity in male mice.

Preimplantation embryos are particularly vulnerable to environmental perturbations, including those related to assisted reproductive technologies. Invasive embryo manipulations, such as blastomere biopsy, are applied worldwide in clinical settings for preimplantation genetic testing. Mouse models have previously shown that blastomere biopsy may be associated with altered phenotypes in adult offspring.

Predicting Neuropsychological Impairment in Relapsing Remitting Multiple Sclerosis: The Role of Clinical Measures, Treatment, and Neuropsychiatry Symptoms.

Objective: This retrospective observational study aimed to define neuropsychological impairment (NI) profiles and determine the influence of clinical, demographic, and neuropsychiatric measures in specific cognitive domains in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients.

Methods: Ninety-one RRMS patients underwent a neurological examination and a brief neuropsychological assessment. Patients were classified according to the disease-modifying therapies (DMTs) received (platform or high-efficacy).

Individual test-retest reliability of evoked and induced alpha activity in human EEG data.

Diverse psychological mechanisms have been associated with modulations of different EEG frequencies. To the extent of our knowledge, there are few studies of the test-retest reliability of these modulations in the human brain. To assess evoked and induced alpha reliabilities related to cognitive processing, EEG data from twenty subjects were recorded in 58 derivations in two different sessions separated by 49.

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset.

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety.

Long-latency optical responses from the dorsal inferior colliculus of Seba's fruit bat.

We used a novel microendoscope system to record simultaneously optical activity (fluorescence of a calcium indicator dye) and electrical activity (multi-unit activity and local field potentials) from the dorsal inferior colliculus of the echolocating bat, Carollia perspicillata. Optically recorded calcium responses to wide-band noise and to frequency-modulated bursts were recorded at probe depths down to 1300 µm, with the majority of active sites encountered at more shallow depths down to 800 µm. Calcium activity exhibited long latencies, within the time span of 50-100 ms after stimulus onset, significantly longer than onset latencies of either multi-unit activity or local field potentials.

Structural and Functional Refinement of the Axon Initial Segment in Avian Cochlear Nucleus during Development.

The axon initial segment (AIS) is involved in action potential initiation. Structural and biophysical characteristics of the AIS differ among cell types and/or brain regions, but the underlying mechanisms remain elusive. Using immunofluorescence and electrophysiological methods, combined with super-resolution imaging, we show in the developing nucleus magnocellularis of the chicken in both sexes that the AIS is refined in a tonotopic region-dependent manner.

Evaluation of Obesity Management Recorded in Electronic Clinical History: A Cohort Study.

Background: The prevalence of obesity is increasing worldwide. Because of their close proximity to the population, primary care physicians and nurses are in a unique position to motivate and advise patients with obesity on a healthy diet and increased physical activity. Drawing from information recorded in electronic clinical records, we evaluated how the general recommendations included in obesity guidelines are being implemented in routine clinical practice.

Pulmonary function testing in children's interstitial lung disease.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.

Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3.

Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG).

Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133 bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0).

New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease.

We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection.

Principal component analysis of data from NMR titration experiment of uniformly N labeled amyloid beta (1-42) peptide with osmolytes and phenolic compounds.

A simple NMR method to analyze the data obtained by NMR titration experiment of amyloid formation inhibitors against uniformly N-labeled amyloid-β 1-42 peptide (Aβ(1-42)) was described. By using solution nuclear magnetic resonance (NMR) measurement, the simplest method for monitoring the effects of Aβ fibrilization inhibitors is the NMR chemical shift perturbation (CSP) experiment using N-labeled Aβ(1-42). However, the flexible and dynamic nature of Aβ(1-42) monomer may hamper the interpretation of CSP data.

Multi-angle development of therapeutic methods for Alzheimer's disease.

Recent clinical trial results support the idea that treatment based on the so-called amyloid hypothesis is a promising approach in Alzheimer's disease (AD), but actually, developing effective treatments for AD remains highly challenging. The discovery that neuron-specific sodium pump activity is impaired in AD and other neurodegenerative diseases such as Parkinson's disease has suggested a role for the sodium pump in the pathogenesis of these diseases. This opens up new possibilities for intervention, such as inhibiting the aberrant interaction of the sodium pump with the disease-specific ligand(s) or activating the sodium pump itself or its downstream signalling.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

Objective: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth.

Study Design: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 24 to 31 weeks of gestation.

HHEX promotes myeloid transformation in cooperation with mutant ASXL1.

Additional sex combs-like 1 (ASXL1), an epigenetic modulator, is frequently mutated in myeloid neoplasms. Recent analyses of mutant ASXL1 conditional knockin (ASXL1-MT-KI) mice suggested that ASXL1-MT alone is insufficient for myeloid transformation. In our previous study, we used retrovirus-mediated insertional mutagenesis, which exhibited the susceptibility of ASXL1-MT-KI hematopoietic cells to transform into myeloid leukemia cells.

Cilostazol, a Phosphodiesterase 3 Inhibitor, Moderately Attenuates Behaviors Depending on Sex in the Ts65Dn Mouse Model of Down Syndrome.

People with Down syndrome, which is a trisomy of chromosome 21, exhibit intellectual disability from infancy and neuropathology similar to Alzheimer's disease, such as amyloid plaques, from an early age. Recently, we showed that cilostazol, a selective inhibitor of phosphodiesterase (PDE) 3, promotes the clearance of amyloid β and rescues cognitive deficits in a mouse model of Alzheimer's disease. The objective of the present study was to examine whether cilostazol improves behaviors in the most widely used animal model of Down syndrome, i.

Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal lung with limited therapeutic options and poor prognosis. Here, we show that conditional deletion of the ubiquitin ligase Nedd4-2 (Nedd4l) in lung epithelial cells in adult mice produces chronic lung disease sharing key features with IPF including progressive fibrosis and bronchiolization with increased expression of Muc5b in peripheral airways, honeycombing and characteristic alterations in the lung proteome. NEDD4-2 is implicated in the regulation of the epithelial Na channel critical for proper airway surface hydration and mucus clearance and the regulation of TGFβ signaling, which promotes fibrotic remodeling.

Comprehensive plaque assessment with serial coronary CT angiography: translation to bedside.

The purpose of this review is to highlight the utility of comprehensive plaque assessment by serial coronary computed tomography angiography (CCTA) to understand atherosclerosis and its effect on cardiovascular risk stratification and management. CCTA is a validated, noninvasive imaging modality for coronary atherosclerotic plaque characterization. Numerous clinical trials have used approach of serial CCTA to demonstrate the potential benefits of multiple treatment strategies to reduce coronary plaque progression and its translation to benefits with cardiovascular outcomes.

Region- and neuronal-subtype-specific expression of Na,K-ATPase alpha and beta subunit isoforms in the mouse brain.

Na,K-ATPase is a ubiquitous molecule contributing to the asymmetrical distribution of Na and K ions across the plasma membrane and maintenance of the membrane potential, a prerequisite of neuronal activity. Na,K-ATPase comprises three subunits (α, β, and FXYD). The α subunit has four isoforms in mice, with three of them (α1, α2, and α3) expressed in the brain.

The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc.

Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder characterized by intellectual disability, developmental delays, microcephaly, and characteristic dysmorphisms. Biallelic mutations of UBE3B, encoding for a ubiquitin ligase E3B are causative for KOS. In this report, we characterize neuronal functions of its murine ortholog Ube3b and show that Ube3b regulates dendritic branching in a cell-autonomous manner.

Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.

Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice.