Epidemiology and genetic characterization of human metapneumovirus in pediatric patients

alexandrossfakianakis shared this article with you from Inoreader Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China via Journal of Medical Virology Abstract Human metapneumovirus (HMPV), which is distributed worldwide, is a significant viral respiratory pathogen responsible for causing acute respiratory tract infections (ARTIs) in children. The aim of the present study was to investigate the epidemiological and genetic characteristics of HMPV in pediatric patients in Hangzhou China following the peak of onset of COVID-19. A total of 1,442 throat swabs were collected from the pediatric patients with a diagnosis of ARTI from November 2020 to March 2021. The following viruses were detected by real-time PCR analysis: HMPV, RSV, adenovirus, hPIV1-3, influenza A, and influenza B. A two-step method was used to amplify the F genes of the HMPV-positive samples. Following sequencing, phylogenetic analyses were conducted using the MEGA version 7 software package. Among the 1,442 samples, 103 (7.14%) were positive for HMPV. No significant differences were observed in the gender distribution. The highest incidence of HMPV oc curred in children older than 6 years and the lowest was noted in children younger than 6 months. Lower respiratory tract infections were diagnosed at a higher rate than upper respiratory tract infections in HMPV-infected children. Only 10 HMPV-infected children (5.41%) were inpatients compared with 93 outpatients (7.39%). Co-infection was observed in 31 HMPV-positive samples including 24 samples of double infection and 7 samples of triple infection. A total of 61 F gene fragments of HMPV, which were approximately 727 bp in length were successfully sequenced. All the HMPVs belonged to the genotype B and were clustered into subgenotypes B1 (1.6%, 1/61) and B2 (98.4%, 60/61). A total of 4 specific amino acid substitutions were noted as follows: aa280, aa296, aa392, and aa396. These substitutions were present between sequences derived from the subgenotypes B1 and B2 in the fusion open reading frame from position 244 to 429. In conclusion, the present study provided significant informat ion regarding the epidemiological and genetic characteristics of HMPV in children living in Hangzhou. Following the first peak of the COVID-19 pandemic, HMPV was considered an important viral respiratory pathogen present in children with ARTI. This article is protected by copyright. All rights reserved. View on Web

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Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis

alexandrossfakianakis shared this article with you from Inoreader Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis via Neuro-Oncology Advance Access Abstract Background Patients with HER2-positive breast cancer (HER2+BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer. Leptomeningeal progression results in a drastically altered prognosis with limited therapeutic options. This phase II study was conducted in order to assess the efficacy of intrathecal (IT) trastuzumab in HER2+BC patients with leptomeningeal metastasis (LM), based on a phase I dose-escalation study that had determined the recommended weekly dose of 150 mg for phase II. Methods Eligible patients received weekly administrations of 150 mg of IT trastuzumab. The primary endpoint was clinical neurologic progression-free survival (LM-related-PFS) after 8 weeks. Overall survival (OS), toxicities and quality of life (QoL) were secondary endpoints. Results Among the 19 enrolled patients, 16 (84%) had concomitant brain metastases, 15 of them had re ceived prior radiotherapy to the brain. All patients had received at least one line of systemic anti-HER2 therapy.After 8 weeks, 14 patients (74%) were free of neurological progression. The median LM-related-PFS was 5.9 months and the median OS was 7.9 months. According to the QLQ-C30 and BN20 scales, the global health-related QoL status seemed preserved and no toxicity above grade 3 was observed. Conclusions Conducting studies on patients with LM poses significant challenges and ethical dilemmas inherent to this population. Despite some limits, this phase II study's findings in terms of clinical neurologic response and quality of life's control confirms weekly administration of 150 mg of IT trastuzumab as a valuable option for HER+BC patients with LM and support the interest for further investigations. View on Web

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Atypical TDP‐43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP

alexandrossfakianakis shared this article with you from Inoreader Atypical TDP‐43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP via Brain Pathology In this study Cooper-Knock et al identified an autosomal dominant ALS pedigree associated with p.Y374X-TARDBP. In patient tissue the authors confirmed reduced TDP-43 protein expression, abnormal TDP-43 fragmentation and deficient TDP-43-mediated splicing. This work extends the phenotypes associated with TDP-43 mutations. Abstract We describe an autosomal dominant, multi-generational, amyotrophic lateral sclerosis (ALS) pedigree in which disease co-segregates with a heterozygous p.Y374X nonsense mutation within TDP-43. Mislocalization of TDP-43 and formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions is the hallmark pathology in >95% of ALS patients. Neuropathological examination of the single case for which CNS tissue was available indicated typical TDP-43 pathology within lower motor neurons, but classical TDP-43-positive inclusions were absent from motor cortex. The mutated allele is transcribed and translated in patient fibroblasts and motor cortex tissue, but overall TDP-43 protein expression is reduced compared to wild-type controls. Despite absence of TDP-43-positive inclusions we confirmed deficient TDP-43 splicing function within motor cortex tissue. Furthermore, urea fractionation and mass spectrometry of motor cortex tissue carrying the mutation revealed atypical TDP-43 prote in species but not typical C-terminal fragments. We conclude that the p.Y374X mutation underpins a monogenic, fully penetrant form of ALS. Reduced expression of TDP-43 combined with atypical TDP-43 protein species and absent C-terminal fragments extends the molecular phenotypes associated with TDP-43 mutations and with ALS more broadly. Future work will need to include the findings from this pedigree in dissecting the mechanisms of TDP-43-mediated toxicity. View on Web

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A reappraisal of microbiome dysbiosis during experimental periodontitis”

alexandrossfakianakis shared this article with you from Inoreader A reappraisal of microbiome dysbiosis during experimental periodontitis" via Molecular Oral Microbiology Abstract Periodontitis is a chronic inflammatory disease associated with the presence of dysbiotic microbial communities. Several studies interrogating periodontitis pathogenesis have utilized the murine ligature-induced periodontitis (LIP) model, and have further examined the ligature-associated microbiome relying on 16SrRNA-based sequencing techniques. However, it is often very challenging to compare microbial profiles across studies, due to important differences in bioinformatic processing and databases used for taxonomic assignment. Thus, our study aim was to re-analyze microbiome sequencing data-sets from studies utilizing the LIP model, through a standardized bioinformatic analysis pipeline, generating a comprehensive overview of the microbial dysbiosis during experimental periodontitis. We conducted a re-analysis of 16SrRNA gene sequencing datasets from 9 published studies utilizing the LIP model. Reads were grouped according the hypervariable region of the 16SrRNA gene amplified (V1-V3 and V4), preprocessed, binned into Operational Taxonomical Units (OTUs) and classified utilizing relevant databases. Alpha and beta-diversity analyses were conducted, alongside relative abundance profiling of microbial communities. Our findings revealed similar microbial richness and diversity across studies, and determined shifts in microbial community structure determined by periodontitis induction and study of origin. Clear variations in the relative abundance of bacterial taxa were observed starting day 5 after ligation and onwards, consistent with a distinct microbial composition during health and experimental periodontitis. We also uncovered differentially represented bacterial taxa across studies, dominating periodontal health and LIP-associated communities. Collectively, this re-analysis provides a unified overview of microbial dysbiosis during the LIP model, providing new insights that aim to inform further studies dedicated to unravelling oral host-microbial interactions. This article is protected by copyright. All rights reserved View on Web

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Protein interactome mapping of Porphyromonas gingivalis provides insights into the formation of the PorQ‐Z complex of the type IX secretion system

alexandrossfakianakis shared this article with you from Inoreader Protein interactome mapping of Porphyromonas gingivalis provides insights into the formation of the PorQ‐Z complex of the type IX secretion system via Molecular Oral Microbiology Abstract Porphyromonas gingivalis is an anaerobic gram-negative human oral pathogen highly associated with the more severe forms of periodontal disease. P. gingivalis utilizes the type IX secretion system (T9SS) to transport ∼30 cargo proteins including multiple virulence factors to the cell surface. The T9SS is a multi-protein complex consisting of at least 19 proteins and recently we characterised the protein interactome of these components. Like the T9SS, almost all biological processes are mediated through protein-protein interactions (PPIs). Therefore, mapping PPIs are important to understand the biological functions of many proteins in P. gingivalis. Herein, we provide native migration profiles of over 1000 P. gingivalis proteins. Using the T9SS, we demonstrate that our dataset is a useful resource for identifying novel protein interactions. Using this dataset and further analysis of T9SS P. gingivalis mutants we discover new mechanistic insights into the formation of the PorQ-Z complex of the T9SS. This dataset is a valuable resource for studies of P. gingivalis. This article is protected by copyright. All rights reserved View on Web

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Analysis of Th cell subsets in local and systemic environments from experimental periodontitis rats

alexandrossfakianakis shared this article with you from Inoreader Analysis of Th cell subsets in local and systemic environments from experimental periodontitis rats via Molecular Oral Microbiology Abstract Objectives: To explore the effect of periodontitis on Th cell subsets in local and systemic environments. Methods: 32 male Sprague-Dawley rats were randomly divided into periodontitis and control groups. Silk ligatures were applied to the mandibular first (M1) molars in the periodontitis group. Inflammation and alveolar bone loss around the M1 molars were analyzed by histological staining and micro-computed tomography. The mRNA expression of IFN-γ, IL-4, IL-17 and IL-10 in the gingiva were detected by qRT-PCR. The proportions of Th1, Th2, Th17 and Treg cells in the submandibular lymph nodes, peripheral blood and jaw bone marrow were tested using flow cytometry. Results: More inflammatory cells and alveolar bone resorption was found in the periodontitis group, with upregulated mRNA expression of IFN-γ, IL-17 and IL-10. The proportion of Th1 and Th17 cells was significantly elevated in submandibular lymph nodes, and the proportion of Th1, Th2 and Th17 cells was significantly elevated in peripheral blood, while the proportion of Th1, Th17 and Treg cells was significantly elevated in jaw bone marrow in the periodontitis group. Conclusion: This study suggests periodontitis affects the differentiation of Th cell subsets in both local and systemic environments, resulting in an increased proportion of proinflammatory cells. This article is protected by copyright. All rights reserved View on Web

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Circadian Pain Patterns in Human Pain Conditions – A Systematic Review

alexandrossfakianakis shared this article with you from Inoreader Circadian Pain Patterns in Human Pain Conditions – A Systematic Review via Pain Practice Abstract Background Chronobiology is the science of how physiological processes in the body follow a pattern of time. Pain has been shown to follow a circadian rhythm, with different types of pain having variable expression along this rhythm. Objective This article reviews the nature of diurnal variations in pain along with a discussion of the mechanisms of circadian rhythm of pain. Evidence Review We conducted a literature search on the PubMed and Google Scholar electronic databases, through April 2022. Publications were screened for English language, full-text availability, and human subjects. Randomized controlled trials and observational trials were included. Data was extracted from studies on patients with acute or chronic pain phenotypes, which provide pain severity data and corresponding diurnal time points. Findings The literature search led to the inclusion of 39 studies. A circadian pattern of pain was found to be present in nociceptive, neuropathic, central and mixed pain states. Postoperative pain, fibromyalgia, trigeminal neuralgia and migraines were associated with higher pain scores in the morning. Temporomandibular joint pain, neuropathic pain, labor pain, biliary colic and cluster headaches increased throughout the day to reach a peak in the evening or night. Arthritis and cancer pain were not associated with any circadian rhythmicity. Furthermore, the circadian rhythm of pain was not found to be altered in patients on analgesics. Conclusion The results of this review suggest that an understanding of diurnal variation may help improve therapeutic strategies in pain management, for instance through analgesic titration. View on Web

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Presenting Symptomatology for Patients With Nasal Septal Perforation: Application of the NOSE‐Perf Scale

alexandrossfakianakis shared this article with you from Inoreader Presenting Symptomatology for Patients With Nasal Septal Perforation: Application of the NOSE‐Perf Scale via The Laryngoscope The NOSE-Perf scale is a patient-reported outcome measure specific to nasal septal patients. NOSE-Perf data are presented for a large heterogenous group of patients. Objective To objectively identify and quantitate presenting nasal symptoms in patients with a septal perforation using the validated NOSE-Perf scale. Study Design Case series retrospective review. Methods The medical records from August 2018 through January 2022 of patients at a tertiary care academic center with a septal perforation, and who completed the NOSE-Perf questionnaire, were reviewed. Perforation symptoms were identified and quantified using the 12-item NOSE-Perf scale (score range 0–48). NOSE-Perf findings were correlated to patient demographics, perforation etiology, and perforation length. NOSE-Perf scores of patients who pursued treatment were compared with those who did not. Results NOSE-Perf data were collected from 202 patients. Nasal crusting was noted in 94.1% of patients and was the most severe symptom reported (mean 2.9 of 4.0). Nasal congestion, difficulty breathing, and nasal obstruction followed in prevalence and severity. The mean total NOSE-Perf score was 23.7. Linear regression analysis demonstrated a weakly negative association of NOSE-Perf score with patient age and weakly positive association with increasing perforation length. NOSE-Perf scores were significantly higher in women and in patients pursuing treatment. Conclusion This is the first study to use the validated NOSE-Perf scale to objectively characterize and establish baseline septal perforation symptomatology. The NOSE-Perf scale can play a role in the standardization of perforation evaluation and treatment outcomes assessment. Laryngoscope, 2022 View on Web

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