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Although several adult rat models of medial temporal lobe epilepsy (mTLE) have been described in detail, our knowledge of mTLE epileptogenesis in infant rats is limited. Here, we present a novel infant rat model of mTLE (InfRPil‐mTLE) based on a repetitive, triphasic injection regimen consisting of low‐dose pilocarpine administrations (180 mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The model had a survival rate of >80% and exhibited characteristic spontaneous recurrent electrographic seizures (SRES) in both the hippocampus and cortex that persisted into adulthood. Using implantable video‐EEG radiotelemetry, we quantified a complex set of seizure parameters that demonstrated the induction of chronic electroencephalographic seizure activity in our InfRPil‐mTLE model, which predominated during the dark cycle. We further analyzed selected candidate genes potentially relevant to epileptogenesis using a RT‐qPCR approach. Several candidates, such as the low‐voltage‐activated Ca2+ channel Cav3.2 and the auxiliary subunits β1 and β2, which were previously reported to be upregulated in the hippocampus of the adult pilocarpine mTLE model, were found to be downregulated (together with Cav2.1, Cav2.3, M1, and M3) in the hippocampus and cortex of our InfRPil‐mTLE model. From a translational point of view, our model could serve as a blueprint for childhood epileptic disorders and further contribute to antiepileptic drug research and development in the future. [ABSTRACT FROM AUTHOR]

Background: Variant-adapted COVID-19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre-existing immunity by original vaccines or prior infections., Aim: To assess whether such immunity sufficiently combats the highly immune-evasive SARS-CoV-2 JN.1 variant., Methods: Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5-adapted vaccines (IBD: n = 18). Neutralisation and anti-receptor-binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild-type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines (secondary outcomes)., Results: Following original vaccines, JN.1 neutralisation was lower than wild-type neutralisation in all study groups (healthy, anti-TNF and non-anti-TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti-TNF: 98.3% and non-anti-TNF: 92.3%). Confounder-adjusted multivariable modelling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre-vaccination vs. 44.4% post-vaccination; p = 0.003)., Conclusions: Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID-19 surges., (© 2024 John Wiley & Sons Ltd.)

Background: Despite findings from translational and genetic studies in the event-related potential (ERP) literature, the validity and reliability of P50 suppression as a schizophrenia spectrum endophenotype has been questioned. Here, we aimed to examine sensory registration and gating measures derived from P50 and N100 amplitude, as well as N100 area-a novel approach proposed herein-in early psychosis versus health., Methods: Individuals at clinical high risk for psychosis (CHR; n = 77), first-episode psychosis (FE; n = 52), and healthy controls (HC; n = 65) were assessed in a paired-click auditory ERP paradigm. Eight CHR converted to psychosis (CHRC) and 39 did not (CHR-NC) by 24 months, while 30 CHR were lost to follow-. Group differences, test-retest reliability, and associations with neurocognitive function were assessed in nine ERP measures., Results: Significant differences were observed in N100 S1 amplitude, S1 area, and area difference between HC and FE, as well as in N100 S1 area between HC and CHR, among the total population. Furthermore, significant differences were found in N100 S1 area between HC and CHR-NC (Cliff's delta, Δ = 0.32), as well as in N100 area difference between HC and CHR-C (Δ = 0.55). Both N100 S1 area and area difference demonstrated moderate to acceptable reliability (intraclass correlation coefficients: 0.61-0.78). Processing speed negatively correlated with both N100 S1 area and area difference, while executive function negatively correlated with N100 S1 area alone in CHR and FE., Conclusion: Among the ERP measures studied, N100 area measures may serve as a reliable biomarker of aberrant sensory processing and neurocognition in early psychosis., Competing Interests: Declaration of competing interest Drs. Cadenhead, Light, and Braff contributed to the design of the study. Drs. Machiraju, Wyss and Cadenhead performed the data analyses. Dr. Machiraju assisted with the writing of the manuscript, along with other authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Rapidly progressive osteoarthritis of the hip is an unusual subset of hip osteoarthritis in which a >2 mm/yr rate of joint space narrowing occurs. Rapidly progressive osteoarthritis of the hip has been associated with intra-articular steroid injection, with the incidence of rapidly progressive osteoarthritis of the hip after intra-articular steroid injection ranging from 2.8% to 21%. The occurrence of rapidly progressive osteoarthritis of the hip unrelated to intra-articular steroid injection is rare, and not frequently reported. This report presents a unique case of rapidly progressive osteoarthritis of the hip in the bilateral hips of one patient. The first hip developed rapidly progressive osteoarthritis of the hip within 6 mos after an intra-articular steroid injection. Three years later, the second hip developed rapidly progressive osteoarthritis of the hip within 4 mos without any injection or use of systemic steroid medication. The etiology of rapidly progressive osteoarthritis of the hip in the absence of intra-articular steroid injection is unclear, and this case presents the opportunity to observe the development of rapidly progressive osteoarthritis of the hip due to different causes within the same individual., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The interspinous region is an atypical source of low back pain, and it can often be difficult to identify. There are many structural components in the interspinous region that can contribute to interspinous pain, including the interspinous ligament, which plays a role in providing stabilization to the spine. Successful treatments of interspinous pain have not been well characterized in the literature. This case presents the first documentation of the use of extracorporeal shockwave therapy as a noninvasive treatment for refractory interspinous-related low back pain. Extracorporeal shockwave therapy has previously been shown to facilitate regeneration and tissue healing in tendons and ligaments but has not previously been used to treat interspinous pain. A 24-yr-old former collegiate softball player presented with 5 mos of low back pain; the interspinous ligament was clinically suspected as a pain generator, and this was confirmed via an ultrasound-guided injection. She underwent a course of physical therapy that improved function but did not improve pain, and nonsteroidal anti-inflammatory drugs only provided minimal and temporary relief. Three consecutive extracorporeal shockwave therapy treatment sessions provided 90% improvement in pain and function, and she was able to return to exercise and recreational sports. At more than 6 mos after extracorporeal shockwave therapy treatment, she reported no recurrences or functional limitations., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Liver steatosis is the most frequent liver disorder and its advanced stage, non-alcoholic steatohepatitis (NASH), will soon become the main reason for liver fibrosis and cirrhosis. The "multiple hits hypothesis" suggests that progression from simple steatosis to NASH is triggered by multiple factors including the gut microbiota composition. The Epstein Barr virus induced gene 2 (EBI2) is a receptor for the oxysterol 7a, 25-dihydroxycholesterol synthesized by the enzymes CH25H and CYP7B1. EBI2 and its ligand control activation of immune cells in secondary lymphoid organs and the gut. Here we show a concurrent study of the microbial dysregulation and perturbation of the EBI2 axis in a mice model of NASH.We used mice with wildtype, or littermates with CH25H -/- , EBI2 -/- , or CYP7B1 -/- genotypes fed with a high-fat diet (HFD) containing high amounts of fat, cholesterol, and fructose for 20 weeks to induce liver steatosis and NASH. Fecal and small intestinal microbiota samples were collected, and microbiota signatures were compared according to genotype and NASH disease state.We found pronounced differences in microbiota composition of mice with HFD developing NASH compared to mice did not developing NASH. In mice with NASH, we identified significantly increased 33 taxa mainly belonging to the Clostridiales order and/ or the family, and significantly decreased 17 taxa. Using an Elastic Net algorithm, we suggest a microbiota signature that predicts NASH in animals with a HFD from the microbiota composition with moderate accuracy (area under the receiver operator characteristics curve = 0.64). In contrast, no microbiota differences regarding the studied genotypes (wildtype vs knock-out CH25H -/- , EBI2 -/- , or CYP7B1 -/- ) were observed.In conclusion, our data confirm previous studies identifying the intestinal microbiota composition as a relevant marker for NASH pathogenesis. Further, no link of the EBI2 - oxysterol axis to the intestinal microbiota was detectable in the current study., (© 2024. The Author(s).)

Purpose: Pediatric patients with cancer often develop chemotherapy-induced fever in neutropenia (FN), requiring emergency broad-spectrum antibiotics. Continuous temperature monitoring can lead to earlier FN detection and therapy with improved outcomes. We aimed to compare the feasibility of continuous core temperature monitoring with timely data availability between two wearable devices (WDs) in pediatric oncology patients undergoing chemotherapy., Methods: In this prospective observational two-center study, 20 patients (median age: 8 years) undergoing chemotherapy simultaneously wore two WDs (CORE®, Everion®) for 14 days. The predefined goal was core temperature recorded in sufficient quality and available within ≤ 30 min during ≥ 18/24 h for ≥ 7/14 days in more than 15 patients., Results: More patients reached the goal with CORE® (n = 13) versus Everion® (n = 3) (difference, 50% p < 0.001). After correcting for the transmission bottleneck caused by two WDs transmitting via one gateway, these numbers increased (n = 15 versus n = 14; difference, 5%; p = 0.69). CORE® measurements corresponded better to ear temperatures (n = 528; mean bias, - 0.07 °C; mean absolute difference, 0.35 °C) than Everion® measurements (n = 532; - 1.06 °C; 1.10 °C). Acceptance rates for the WDs were 95% for CORE® and 89% for Everion®., Conclusion: The CORE® fulfilled the predefined feasibility criterion (15 of 20 patients) after correction for transmission bottleneck, and the Everion® nearly fulfilled it. Continuous core temperature recording of good quality and with timely data availability was feasible from preschool to adolescent patients undergoing chemotherapy for cancer. These results encourage the design of randomized controlled trials on continuously monitored core temperature in pediatric patients., Clinicaltrials: gov (NCT04914702) on June 7, 2021., (© 2024. The Author(s).)

Fluent and automatized handwriting frees cognitive resources for more complex elements of writing (i.e., spelling or text generation) or even math tasks (i.e., operating) and is therefore a central objective in primary school years. Most previous research has focused on the development of handwriting automaticity across the school years and characteristics of handwriting difficulties in advanced writers. However, the relative and absolute predictive power of the different kinematic aspects for typically developing beginning handwriting remains unclear. The purpose of the present study was to investigate whether and to what extent different kinematic aspects contribute to handwriting proficiency in typically developing beginning handwriters. Further, we investigated whether gender, socioeconomic background, or interindividual differences in executive functions and visuomotor integration contribute to children's acquisition of handwriting. Therefore, 853 first-grade children aged seven copied words on a digitized tablet and completed cognitive performance tasks. We used a confirmatory factor analysis to investigate how predefined kinematic aspects of handwriting, specifically the number of inversions in velocity (NIV), pen stops, pen lifts, and pressure on the paper, are linked to an underlying handwriting factor. NIV, pen stops, and pen lifts showed the highest factor loadings and therefore appear to best explain handwriting proficiency in beginning writers. Handwriting proficiency was superior in girls than boys but, surprisingly, did not differ between children from low versus high socioeconomic backgrounds. Handwriting proficiency was related to working memory but unrelated to inhibition, shifting, and visuomotor integration. Overall, these findings highlight the importance of considering different kinematic aspects in children who have not yet automatized pen movements. Results are also important from an applied perspective, as the early detection of handwriting difficulties has not yet received much research attention, although it is the base for tailoring early interventions for children at risk for handwriting difficulties., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Truxius et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)