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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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Endoscopic trans‐lateral oropharyngeal wall approach to the petrous apex and the petroclival region

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Abstract

Background

A trans-lateral oropharyngeal wall approach (TLOWA) to the petrous apex has not been previously defined. This study aims to assess the feasibility of a TLOWA for surgical access to the petrous apex and the petroclival region.

Methods

An endoscopic TLOWA for exposure of the petrous apex and petroclival region was performed on five cadaveric specimens (10 sides). Associated anatomical landmarks were defined, and the strategies for maximal exposure of the internal carotid artery (ICA) were explored.

Results

Via a TLOWA, the parapharyngeal ICA was widely exposed in all 10 sides. Following transection of the Eustachian tube, the inferior petrous apex and petroclival region could be sufficiently exposed. After drilling the anteroinferior bony canal, the horizontal petrous ICA, foramen lacerum, and the paraclival ICA could be adequately revealed.

Conclusion

The TLOWA may provide an alternative corridor for access to the petrous apex and the petroclival region. The parapharyngeal, petrous, lower paraclival ICAs, and the foramen lacerum could be adequately exposed via the TLOWA.

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

alexandrossfakianakis shared this article with you from Inoreader

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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