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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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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Concordance of B and T cell responses to SARS‐CoV‐2 infection, irrespective of symptoms suggestive of COVID‐19

alexandrossfakianakis shared this article with you from Inoreader Concordance of B and T cell responses to SARS‐CoV‐2 infection, irrespective of symptoms suggestive of COVID‐19 via Journal of Medical Virology Abstract Objectives To assess T cell responses in individuals with and without a positive antibody response to SARS-CoV-2, in symptomatic and asymptomatic individuals during the COVID-19 pandemic. Methods Participants were drawn from the TwinsUK cohort, grouped by a) presence or absence of COVID-associated symptoms (S+, S-), logged prospectively through the COVID Symptom Study app, and b) Anti-IgG Spike and anti-IgG Nucleocapsid antibodies measured by ELISA (Ab+, Ab-), during the first wave of the UK pandemic. T cell helper and regulatory responses after stimulation with SARS-CoV-2 peptides were assessed. Results 32 participants were included in final analysis. 14 of 15 with IgG Spike antibodies had a T cell response to SARS-CoV-2-specific peptides; none of 17 participants without IgG Spike antibodies had a T cell response (Chi-squared 28.2, p<0.001). Quantitative T cell responses correlated strongly with fold-change in IgG Spike antibody titre (rho=0 .79, p<0.0001) but not to symptom score (rho=0.17, p=0.35). Conclusions Humoral and cellular immune responses to SARS-CoV-2 are highly correlated. We found no evidence of cellular immunity suggestive of SARS-CoV2 infection in individuals with a COVID-19-like illness but negative antibodies. This article is protected by copyright. All rights reserved. View on Web

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Sustained within-season vaccine effectiveness against influenza-associated hospitalization in children: Evidence from the New Vaccine Surveillance Network, 2015-2016 through 2019-2020

alexandrossfakianakis shared this article with you from Inoreader Sustained within-season vaccine effectiveness against influenza-associated hospitalization in children: Evidence from the New Vaccine Surveillance Network, 2015-2016 through 2019-2020 via Clinical Infectious Diseases Advance Access Abstract Background Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited. Methods We conducted a prospective, test-negative study of children 6 months–17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression. Results Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were v accinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant. Conclusions We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children. View on Web

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DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients

alexandrossfakianakis shared this article with you from Inoreader DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients via Neuro-Oncology Advance Access Abstract Background DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. Methods Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as surgical benefit for recurrent glioblastoma. Results 345 patients (80.2%) fulfilled the inclusion criteria. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (p = 0.06). 305 Patients receiving combined adjuvant therapy (RTK I: Ref. ; RTK II: HR 0.9 [95% CI, 0.64-1.28]; p = 0.56; MES: 0.69 [0.47-1.02]; p = 0.06). RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36-6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80-9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68-3.09]; p = 0.33). Therapy response-predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19-0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34-0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27-1.02]; p = 0.06). For local recurrence (n=112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33). Conclusion We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at tim e of recurrence. View on Web

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Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia‐Pacific

alexandrossfakianakis shared this article with you from Inoreader Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia‐Pacific via Journal of Medical Virology Abstract Introduction: Liver disease is a growing burden among PLHIV in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Methods: Patients on cART with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels >5 times its upper limit of normal) were analysed using repeated measure logistic regression over a ten-year follow-up period. Liver cirrhosis was defined as having an APRI score >1.5, FIB-4 score >3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyse factors associated with cirrhosis among those in follow-up after 2015. Results: Of 5182 patients, 101 patients (1.9%) had high ALT levels with HCV-antibody positive (OR 4.98, 95%CI 2.82-8.77, p <0.001) an d ever high alcohol consumption (OR 2.33, 95% CI 1.00-5.46, p=0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate= 0.82 per 100 person-years). Those HCV-antibody positive (HR 5.54, 95% CI 3.75-8.18, p<0.001) and had high alcohol consumption (HR 2.06, 95%CI 1.23-3.45, p=0.006) were associated with liver cirrhosis. Conclusion: HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reduce the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol. This article is protected by copyright. All rights reserved. View on Web

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Interferon‐gamma inducible protein 16 and type I interferon receptors expression in experimental apical periodontitis induced in wild type mice

alexandrossfakianakis shared this article with you from Inoreader Interferon‐gamma inducible protein 16 and type I interferon receptors expression in experimental apical periodontitis induced in wild type mice via International Endodontic Journal Abstract Aim The aim of this study was to evaluate the IFI16 and IFN-α/β receptors expression during the genesis and development of experimental apical periodontitis (AP) in mice teeth. Methodology AP was induced in the lower first molars of 40 C57BL/6 mice. They were divided according to the experimental periods 2, 7, 14, 21 and 42 days (n=8 per group). Five animals were used as a control group (without AP). Specimens were submitted to histological processing for description of the inflammatory process, immunostaining for the presence/absence and localization of IFI16 and IFN-α/β receptors (qualitative and semi-quantitative analysis), and tartrate-resistant acid phosphatase (TRAP) histoenzimology. Results The results showed a gradual development of AP over the experimental times. The expression of IFI16 was noticeably more exacerbated in the experimental early period (day 2) while the lowest expression was observed in the control group (p=0.02). For IFN-α/β receptors, a higher intensity staining was observed 42 days after AP induction, that was statistically different from the control group (p=0.02). Also, the number of TRAP positive cells was higher on the later periods (days 21 and 42) (p<0.001). Conclusion IFI16 protein expression was highest during the early periods after apical periodontitis induction in mice teeth, whilst IFN-α/β receptors expression was highest after apical periodontitis became established. View on Web

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Protective Effects of Cannabis sativa on chemotherapy‐induced nausea

alexandrossfakianakis shared this article with you from Inoreader Protective Effects of Cannabis sativa on chemotherapy‐induced nausea in a rat: Involvement of CB1 receptors via Fundamental & Clinical Pharmacology Abstract Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa (C. sativa) and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (8 animals per group): Group 1: Normal control (saline i.p). Group 2: rats received cyclophosphamide (200 mg/kg i.p) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg ip) across days 1 – 7 and C. sativa (20 and 40 mg/kg sc) was administered on cyclophosphamide days 4 – 7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestina l homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5HT, dopamine and noradrenaline, as well as, decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa, also, improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R. View on Web

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Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

alexandrossfakianakis shared this article with you from Inoreader Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation via Transplant Infectious Disease Abstract Background Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified. Methods We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic SCT recipients. Patients who underwent SCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control. Results The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs 71.6%, P < 0.05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs 19.8%, P < 0.05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (HR = 2.76, 95% confidence interval 1.14 – 6.68, P < 0.05). Conclusion Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis. This article is protected by copyright. All rights reserved View on Web

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