Metformin and Infections: What Is the Next Step in This Decades-Long Story?

alexandrossfakianakis shared this article with you from Inoreader Metformin and Infections: What Is the Next Step in This Decades-Long Story? via Clinical Infectious Diseases Advance Access metforminmedical historyadjunctive therapyinfectious diseases View on Web

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Bartonella quintana transmitted by head lice: an outbreak of trench fever in Senegal

alexandrossfakianakis shared this article with you from Inoreader Bartonella quintana transmitted by head lice: an outbreak of trench fever in Senegal via Clinical Infectious Diseases Advance Access Abstract Background Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse faeces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood. Methods In Senegal, the implementation of a permanent local surveillance system in a Point-of-Care laboratory (POC) allows the monitoring of emerging diseases. Here, we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of two isolated strains of B. quintana were sequenced and analysed. Results A total of 2,289 blood samples were collected in the 2010-2015 period. From 2010-2013, B. quintana DNA was detected by PCR in 0.25% (4/1,580). In 2014, 228 blood samples were collected, along with 161 head lice from five individuals. B. quintana DNA was detected in 4·4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61·7%, 50/81) and non-febrile patients (61·4%, 43/70). Two B. quintana strains were isolated from blood and head lice from two different patients. Genomic sequence analysis showed 99·98% overall similarity between both strains. Conclusion The presence of live B. quintana in head lice, and the genetic identity of strains from patients' blood and head lice during a localised outbreak in Senegal, supports the evidence of head lice vectorial capacity. View on Web

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Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033

alexandrossfakianakis shared this article with you from Inoreader Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033 via Neuro-Oncology Advance Access Abstract Background Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas. Methods An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) hi stologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power. Results Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm 2) significantly influences PFS (p = 0.0098) and marginally the OS (p = 0.07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data. Conclusion The mitotic index (cut-off 2 per 10 40x HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status. View on Web

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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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