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Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.

Abstract Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P

Background: Audiovestibular disorders in childhood occur with considerable frequency. However, the difficulty of obtaining medical history, the nonspecificity of symptoms, and the lack of cooperation during complementary tests often contribute significantly to diagnostic biases, attributing clinical presentations to psychosomatic disorders. The objectives of this work are, firstly, to characterize, from an auditory and vestibular perspective, the most frequent causes of vertigo in childhood and a possible relationship with emotional symptoms. On the other hand, to propose the usefulness of the MSSQ-Short questionnaire as a predictive variable in the evolution of children diagnosed with recurrent vertigo of childhood (RVC). Methods: An observational cross-sectional study was designed with retrospective data collection at three tertiary hospitals. Results: Among the 117 patients recruited between 2016 and 2024, 32 patients (27.35%) were diagnosed with an anxious-depressive syndrome prior to audiovestibular testing. The mean age was 11.19 ± 5.61 years and the most frequent final diagnoses were vestibular migraine (VM) with 41.03% and RVC with 23.93%. Patients with VM, compared with RVC, are approximately 1.12 times more likely to have psychosomatic pathology (CI 0.39 to 3.25). The most sensitive and frequently altered test was VEMPS (39.32%), with statistical significance in VM and otic capsule dehiscence, while regarding the MSSQ-Short questionnaire, the linear regression of 0.28 indicates an increase in clinical duration with high questionnaire scores. Conclusions: Vestibular disorders causing dizziness and vertigo are challenging to diagnose, often due to lack of cooperation and/or symptom nonspecificity. A thorough medical history and complementary tests, including audiovestibular and imaging studies, are advisable, thus avoiding systematically attributing children’s complaints to other psychosomatic disorders.

This study used the Community of Inquiry framework to examine how university instructors designed, facilitated, and supported social and cognitive processes in online courses, and how instructors and students experienced these processes. In early 2021, 25 online focus groups were organized with instructors (n = 52) and students (n = 44) from all faculties of a large Dutch university to discuss this. In terms of design, instructors restructured their courses (e.g. reduced group sizes to intensify interaction and implemented a flipped classroom approach) and communicated more explicitly about the course structure and expectations to better enable students to self-regulate their learning process. During the course, instructors orchestrated cognitive and social processes by facilitating discourse (e.g. breakout room activities and collaboration activities) and offering direct support (e.g. online progress monitoring and "being there" for students). The analysis illustrated how teaching presence plays a crucial role in fostering cognitive and social processes in online courses. This study contributes to a better understanding of the role of teaching presence in a community of inquiry, while providing insights that can inform the development of effective online teaching strategies.

The objective of this work is to create, and validate, a questionnaire aimed at assessing those actions undertaken by school management teams to promote inclusion in compulsory education sector in Spain. It is based on the perspective of teaching teams (members of management teams and teachers). To determine the psychometric properties of the questionnaire a descriptive, exploratory factorial and confirmatory factorial analysis was performed. In the pilot phase of the instrument, 243 members of teaching teams participated. The results obtained confirm that it is a valid and reliable scale with a bifactorial structure. The first of these factors includes actions carried out by the management teams to energise inclusive culture in their schools and thus turn them into inclusive communities. The other set of actions includes interventions with the aim of improving the training of students and creating professional learning communities.

This study analyses teachers' opinions concerning the actions taken by management teams in favor of policies which address inclusion in compulsory education schools in Granada (Spain). This is quantitative research in which the LIE-Q-Teaching Team has been used. Two hundred forty-three teachers participated in this study which involved a descriptive and inferential analysis. Results show that the actions promoting inclusion mainly relate to the management of teaching-learning processes and professional development. Results also reveal that there are significant differences based on the ownership of the school, its educational level and the socio-economic status of the area in which it is located.

Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1+ cells located within the arachnoid beneath and separate from E-cadherin+ arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.

Objective: The COVID-19 pandemic affected neuro-oncological patients and their caregivers regarding tumor care and emotional functioning, including Quality of Life (QoL). This study aimed to understand how COVID-19 affected their psychological state and the relations between patients and health personnel in neuro-oncology. Methods: A cross-sectional study was conducted on neuro-oncological patients and their caregivers. Results: A total of 162 patients and 66 caregivers completed the questionnaire. Altogether, 37.5% of patients perceived a greater risk of contracting COVID-19 compared to the general population. On a 0–10 scale, the patients’ tumor-related anxiety score was 5.8, and their COVID-19-related score was 4.6. The caregivers reported 7.7 and 5.5, respectively. QoL was described as at least good in 75% of both patients and caregivers; the caregivers’ care burden increased in 22.7% of cases during the pandemic, with no correlation with QoL. Future perception often changed, both in patients and caregivers. In 18% of cases, the cancer treatment schedule was changed, either by patient decision or by medical decision. However, 93.5% of patients were satisfied with their overall care. Conclusions: A considerable proportion of patients and caregivers still perceived the tumor disease as more burdensome than the pandemic, and their future as more uncertain. Such data suggest the need to build a productive alliance between patients and health professionals.

Background Music, a profound human expression, can have physical implications for its practitioners. Musicians face various physical challenges that can impact their well-being, with craniofacial and temporomandibular pain being prevalent yet understudied. Temporomandibular joint disorder (TMJD) affects up to one-third of the population, though prevalence varies by study. While musculoskeletal issues like carpal tunnel syndrome are well-documented in musicians, craniofacial and temporomandibular pain is less explored. This study aims to determine the differences in TMJD frequency among music students of different instrumental specialties. Methods The sample was composed of students between 12 and 25 years of age from the National University of Music of Peru. A stratified random probability sample was chosen. Data were collected using a structured instrument covering general data, academic information, dental malocclusion, the Fonseca Simplified Anamnestic Index, and the Global Stress Perception Scale. Statistical analysis included Pearson's Chi-square test and a generalized linear model regression. Results The sample included 71.4% males with a median age of 23 years. Class II dental occlusion was most common (51.4%). TMJD prevalence was: 14.3% no TMJD, 60.0% mild TMJD, 22.9% moderate TMJD, and 2.9% severe TMJD. Metal wind (PR=0.04, 95%CI [0.00; 50.04], p=0.002) and woodwind players (PR=0.03, 95%CI [0.00; 0.56], p=0.018) had lower TMJD prevalence compared to plucked string and percussion players. Post-regression analysis indicated significant differences between metal wind and percussion students (p=0.030) and between percussion and woodwind students (p=0.025). These results are supported by the adjusted ratio of proportions analysis, which maintains statistical significance. Conclusion We found significant differences in TMJD prevalence among music students based on their instrumental specialty, with lower rates in metal wind and woodwind players compared to plucked string and percussion players.

Summary: Background: Paediatric acute bronchiolitis normally occurs from October to April in the temperate northern hemisphere, peaking in January. Nonpharmacological measures to control the spread of COVID-19 resulted in a decrease in the number of cases of bronchiolitis during the 2020–21 season. The discontinuation of these measures created an uncertain scenario. Aim: To describe the epidemiological evolution of acute bronchiolitis seasons and the changes in the demographics of the affected population before, during, and after the implementation of nonpharmacological interventions for COVID-19 in Spain. Methods: This was a multicentre and descriptive study. A total of 6,334 infants aged up to 12 months who were diagnosed with acute bronchiolitis were recruited from sixteen Spanish hospitals. We collected data from participants from September 1st, 2021, through August 31st, 2023, as part of the ECEALHBA research project. The study periods were before (P1), during (P2), and after (P3) the COVID-19 pandemic. Findings: In P2 and after the discontinuation of nonpharmacological interventions, an unexpected increase in the number of acute bronchiolitis cases was observed from June–August 2021, resulting in an out-of-season peak. A subsequent peak was observed in November 2021, earlier than expected for the 2021-22 season. In the 2022-23 season, admissions followed a historical trend, with a greater number of cases than in the two previous seasons. Statistically significant differences in the length of stay (p

PURPOSEGallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations.METHODSPatients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets.RESULTSA total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024).CONCLUSIONThe prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2–targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.