Construct validity and responsiveness of ASAS Health Index assessed in two longitudinal studies of tumour necrosis factor alpha inhibitor initiation and dose reduction in patients with axial spondyloarthritis.

Background: The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a novel questionnaire of global functioning for patients with axial spondyloarthritis (SpA).

Objective: The objective was to assess the construct validity, discriminatory ability and responsiveness of ASAS HI in relation to patient-reported outcome measures (PROMs), MRI and radiography.

Methods: Data from two longitudinal studies with tumour necrosis factor inhibitor (TNFi) initiation (novel MRI And biomarkers in Golimumab-treated patients with axial spondyloarthritis (MANGO): n=45) respectively tapering (Dose adjustment of Biological treatment in patients with SpA (DOBIS): n=106) were used.

Comparing Time to Recovery Between Initial and Repeat Concussion in Athletes.

Objective: Compare time to recovery between initial and repeat concussions.

Design: Retrospective review of electronic medical record.

Setting: An interdisciplinary concussion clinic.

Orthostatic Vital Signs After Sport-Related Concussion: A Cohort Study.

Background: The 6th International Consensus Statement on Concussion in Sport guidelines identified that measuring autonomic nervous system dysfunction using orthostatic vital signs (VSs) is an important part of the clinical evaluation; however, there are limited data on the frequency of autonomic nervous system dysfunction captured via orthostatic VSs after concussion.

Purpose: To compare orthostatic changes in heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between athletes with acute sport-related concussion (SRC) and control athletes.

Study Design: Cross-sectional study; Level of evidence, 3.

Headache Characteristics of Pediatric Sport-Related Concussion.

Background: Headache is among the most common symptoms following concussion, yet headache after concussion (HAC) remains poorly characterized. This study describes headache characteristics over the first four weeks following pediatric sport-related concussion.

Methods: This is a retrospective case series of 87 athletes (mean: 14.

Antimetastatic effect of intratumoral Treg antagonists in mice with renal cancer.

The interplay of regulatory T cells (Tregs) within the tumour microenvironment presents a significant challenge in anticancer immunotherapy. This study investigates the potential of Treg blockade to enhance the efficiency of effector T cells. Two distinct treatment cocktails were examined: 3p-hpRNA (5' triphosphate hairpin RNA) combined with unmethylated CpG oligonucleotide (CpG); CpG in combination with OX40 receptor-specific monoclonal antibody (anti-OX40).

A CTB-SARS-CoV-2-ACE-2 RBD Mucosal Vaccine Protects Against Coronavirus Infection.

Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity.

Unpacking the modeling process for energy policy making.

This article explores how the modeling of energy systems may lead to an undue closure of alternatives by generating an excess of certainty around some of the possible policy options. We retrospectively exemplify the problem with the case of the International Institute for Applied Systems Analysis (IIASA) global modeling in the 1980s. We discuss different methodologies for quality assessment that may help mitigate this issue, which include Numeral Unit Spread Assessment Pedigree (NUSAP), diagnostic diagrams, and sensitivity auditing (SAUD).

Long-Term Follow-Up of a Family with Retinal Dystrophy Caused by RPE65 Mutation.

We present here the case histories of two siblings, a boy and a girl, with Leber's congenital amaurosis (LCA). The diagnosis was based on non-recordable full-field electroretinogram (ffERG). The long-term ophthalmologic follow-up included kinetic perimetry (Goldmann), visual evoked potentials with flash stimulation, optical coherence tomography (OCT: B-scan images at the area of fovea), and multifocal ERG.

Closed-loop brain stimulation augments fear extinction in male rats.

Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing.

Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents.

Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents.

Asymptomatic and Mild SARS-CoV-2 Infections in a Hungarian Outpatient Cohort in the First Year of the COVID-19 Pandemic.

We aimed to estimate the proportion of the population infected with SARS-CoV-2 in the first year of the pandemic. The study population consisted of outpatient adults with mild or no COVID-19 symptoms and was divided into subpopulations with different levels of exposure. Among the subpopulation without known previous COVID-19 contacts, 4143 patients were investigated.

HCN channels and absence seizures.

Hyperpolarization-activation cyclic nucleotide-gated (HCN) channels were for the first time implicated in absence seizures (ASs) when an abnormal I (the current generated by these channels) was reported in neocortical layer 5 neurons of a mouse model. Genetic studies of large cohorts of children with Childhood Absence Epilepsy (where ASs are the only clinical symptom) have identified only 3 variants in HCN1 (one of the genes that code for the 4 HCN channel isoforms, HCN1-4), with one (R590Q) mutation leading to loss-of-function. Due to the multi-faceted effects that HCN channels exert on cellular excitability and neuronal network dynamics as well as their modulation by environmental factors, it has been difficult to identify the detailed mechanism by which different HCN isoforms modulate ASs.

Metal-oxide inhalation induced fever - Immuntoxicological aspects of welding fumes.

Metal fume fever is a well-known occupational disease that arises from prolonged exposure to subtoxic levels of zinc oxide-containing fumes or dust. This review article aims to identify and examine the possible immunotoxicological effects of inhaled zinc oxide nanoparticles. The current most widely accepted pathomechanism for the development of the disease involves the formation of reactive oxygen species following the entry of zinc oxide particles into the alveolus resulting the release of pro-inflammatory cytokines by activation of the Nuclear Factor Kappa B transcriptional signal, thus evoking the symptoms.

Differential Serotonergic Modulation of Synaptic Inputs to the Olfactory Cortex.

Serotonin (5-hydroxytriptamine, 5-HT) is an important monoaminergic neuromodulator involved in a variety of physiological and pathological functions. It has been implicated in the regulation of sensory functions at various stages of multiple modalities, but its mechanisms and functions in the olfactory system have remained elusive. Combining electrophysiology, optogenetics and pharmacology, here we show that afferent (feed-forward) pathway-evoked synaptic responses are boosted, whereas feedback responses are suppressed by presynaptic 5-HT receptors in the anterior piriform cortex (aPC) in vitro.

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges of absence seizures.

Spike-and-wave discharges (SWDs), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence seizures (ASs). SWDs begin in a cortical initiation network in both humans and animal models, including the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), where it is located in the primary somatosensory cortex (S1). The behavioral manifestation of an AS occurs when SWDs spread from the cortical initiation site to the whole brain, however, the mechanisms behind this rapid propagation remain unclear.

Epigenetic Mechanisms Governing Female and Male Germline Development in Mammals.

Background: DNA methylation (DNAme) and histone posttranslational modifications (PTMs) play an integral role in the transcriptional regulation of specific sets of genes and retrotransposons. In turn, these chromatin marks are essential for cellular reprogramming, including during germline development. While DNAme is stably propagated in most somatic tissues, this epigenetic mark undergoes cycles of widespread erasure and re-establishment in the early embryo as well as in the germline.

Effects of the combination of a monoclonal agonistic mouse anti-OX40 antibody and toll-like receptor agonists: Unmethylated CpG and LPS on an MB49 bladder cancer cell line in a mouse model.

Purpose: The basis of the antitumor immunotherapy, of which the purpose is the stimulation of the immune system. We have used two of the Pathogen Associated Molecular Patterns: unmethylated CpG oligonucleotide, a ligand of Toll-like receptor 9 (TLR9), and lipopolysaccharide (LPS) which is recognized by TLR4, combined with an agonistic OX40 receptor-specific monoclonal antibody (anti-OX40), which is expressed by activated regulatory T-cells (and by other activated T-cell populations as well). The objective of this study was to prove the effectiveness of the aforementioned compounds in an animal model, on a bladder cancer cell line.

Profiling Histone Methylation in Low Numbers of Cells.

Chromatin immunoprecipitation (ChIP) enables the study of DNA-protein interactions. When coupled with high-throughput sequencing (ChIP-seq), this method allows the generation of genome-wide profiles of the distribution of specific proteins in a given cellular context. Typical ChIP-seq experiments require millions of cells as input material and thus are not ideal to study many in vivo cell populations.

Differential Serotonergic Modulation of Principal Neurons and Interneurons in the Anterior Piriform Cortex.

Originating from the brainstem raphe nuclei, serotonin is an important neuromodulator involved in a variety of physiological and pathological functions. Specific optogenetic stimulation of serotonergic neurons results in the divisive suppression of spontaneous, but not sensory evoked activity in the majority of neurons in the primary olfactory cortex and an increase in firing in a minority of neurons. To reveal the mechanisms involved in this dual serotonergic control of cortical activity we used a combination of electrophysiological recordings from identified neurons in the primary olfactory cortex, optogenetics and pharmacology and found that serotonin suppressed the activity of principal neurons, but excited local interneurons.

Temporally Targeted Interactions With Pathologic Oscillations as Therapeutical Targets in Epilepsy and Beyond.

Self-organized neuronal oscillations rely on precisely orchestrated ensemble activity in reverberating neuronal networks. Chronic, non-malignant disorders of the brain are often coupled to pathological neuronal activity patterns. In addition to the characteristic behavioral symptoms, these disturbances are giving rise to both transient and persistent changes of various brain rhythms.