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Δευτέρα 25 Ιουλίου 2022

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

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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.

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

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

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

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Κυριακή 24 Ιουλίου 2022

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

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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.

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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

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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.
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A soluble DR5‐Fc chimeric protein (sDR5‐Fc) attenuates inflammatory responses induced by coronavirus MHV‐A59 and SARS‐CoV‐2

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Abstract

Mortality in COVID-19 patients has been linked to the presence of "cytokine storm" induced by SARS-CoV-2 infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, no significant efficacy has been observed yet, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 (MHV-A59) and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocking the TRAIL-DR5 interaction. Our finding indicates that blocking TRAIL-DR5 pathway through sDR5-Fc chimeric protein is a promising strategy to treat with COVID-19 severe patients requiring ICU admission or with chronic metabolic diseases.

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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

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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.

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Protective Effects of Cannabis sativa on chemotherapy‐induced nausea

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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.

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

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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.

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Πέμπτη 21 Ιουλίου 2022

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial

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Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increas...
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Three-dimensional evaluation of postoperative stability: a comparative study between surgery-first and surgery-late protocols

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The main objective of this study was to compare the stability of the surgery-first and surgery-late approaches according to the standardized centre protocols, by three-dimensional evaluation after 1 year of follow-up. A retrospective study was designed that included a test group (surgery-first protocol) and a control group (surgery-late protocol), with a follow-up period of at least 1 year (average 14 months; range 12 –24 months). Stability was evaluated using linear and angular measurements by superimposing cone beam computed tomography images obtained at specific points in time: preoperatively, 1 month after surgery, and at the end of the orthodontic treatment. (Source: International Journal of Oral and Maxillofacial Surgery)
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