Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation

alexandrossfakianakis shared this article with you from Inoreader Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation via Brain Pathology Abstract Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug-resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, a nd organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia-mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; loc al treatment with anticomplement drugs could in principle modify the course of disease in these patients. View on Web

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Epstein–Barr virus‐positive diffuse large B‐cell lymphoma onset as familial hemophagocytic lymphohistiocytosis in an infant

alexandrossfakianakis shared this article with you from Inoreader Epstein–Barr virus‐positive diffuse large B‐cell lymphoma onset as familial hemophagocytic lymphohistiocytosis in an infant via Pediatric Blood & Cancer View on Web

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Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper via Pediatric Blood & Cancer Abstract A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology. View on Web

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Omicron infection increases IgG binding to spike protein of predecessor variants

alexandrossfakianakis shared this article with you from Inoreader Omicron infection increases IgG binding to spike protein of predecessor variants via Journal of Medical Virology Abstract Background SARS-CoV-2 transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Objectives Residual archival sera (N=81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N=18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). Results We found ~2-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared to the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36-49%) was observed to Omicron spike protein. Conclusions Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants. This article is protected by copyright. All rights reserved. View on Web

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The varied spectrum of nephroblastomatosis, nephrogenic rests, and Wilms tumors: Review of current definitions and challenges of the field

alexandrossfakianakis shared this article with you from Inoreader The varied spectrum of nephroblastomatosis, nephrogenic rests, and Wilms tumors: Review of current definitions and challenges of the field via Pediatric Blood & Cancer Abstract The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care. View on Web

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the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM‐Pt)

alexandrossfakianakis shared this article with you from Inoreader The Portuguese version of the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM‐Pt): translation, cultural adaptation, and multicenter validation study in professional orchestra musicians via Pain Practice Abstract Objectives We aim to assess the validity and reliability of the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM) and to add to its cross-cultural adaptation process by translating, culturally adapting and validating the MPIIQM into European Portuguese language in the population of Portuguese musicians. Methods A Portuguese version of the MPIIQM (MPIIQM-Pt) was created through a process of forward and back translation, pilot testing and cultural adaptation by expert panel evaluation. The psychometric evaluation was performed in a validation sample of 134 musicians, at baseline and after seven days. Results The high degree of internal consistency and the substantial test-retest reliability coefficients were demonstrated for each subscale (α = 0,896 and ICC = 0,997 for "pain intensity", and α = 0,879 and ICC = 0,999 for "pain interference", respectively). Exploratory factor analysis indicated two-factor structure (pain intensity and interference) that explained 75,5% of the variance. Both convergent and divergent validity are well demonstrated, confirming more than 90% of the previously defined hypotheses regarding correlations with other measures. Discussion MPIIQM-Pt is the first validated questionnaire to evaluate pain among Portuguese musicians. It showed excellent psychometric properties, both in terms of internal consistency, test-retest reliability, factor analysis, and construct validity. Therefore, it is a valid and reliable tool suitable for both research and clinical practice purposes. MPIIQM-Pt will allow the development of more robust studies on pain among musicians and the improved assessment and monitoring of pain in this population, filling an important gap in this field of Pain Medicine. View on Web

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Development of machine learning models for the prediction of positive surgical margins in transoral robotic surgery (TORS)

alexandrossfakianakis shared this article with you from Inoreader Development of machine learning models for the prediction of positive surgical margins in transoral robotic surgery (TORS) via Head & Neck Abstract Purpose To develop machine learning (ML) models for predicting positive margins in patients undergoing transoral robotic surgery (TORS). Methods Data from 453 patients with laryngeal, hypopharyngeal, and oropharyngeal squamous cell carcinoma were retrospectively collected at a tertiary referral center to train (n = 316) and validate (n = 137) six two-class supervised ML models employing 14 variables available pre-operatively. Results The accuracy of the six ML models ranged between 0.67 and 0.75, while the measured AUC between 0.68 and 0.75. The ML algorithms showed high specificity (range: 0.75–0.89) and low sensitivity (range: 0.26–0.64) in detecting patients with positive margins after TORS. NPV was higher (range: 0.73–0.83) compared to PPV (range: 0.45–0.63). T classification and tumor site were the most important predictors of positive surgical margins. Conclusions ML algorithms can identify patients with low risk of positive margins and therefore amenable to TORS. View on Web

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