Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, May 3, 2022

Comprehensive Role of SARS‐CoV‐2 Spike Glycoprotein in Regulating Host Signaling Pathway

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Abstract

Since the outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literatures, the characters and pathogenic mechanisms of the virus, epidemiological and clinical features of the disease are rapidly discovered. The spike glycoprotein (S protein), as a key antigen of SARS-CoV-2 for developing vaccines, antibodies, and drug targets, has been shown to play an important role in viral entry, tissue tropism, and pathogenesis. In this review, we summarize the molecular mechanisms of interaction between S protein and host factors, especially receptor-mediated viral modulation of host signaling pathways, and highlight the progression on potential therapeutic targets, prophylactic and therapeutic agents for prevention and treatment of SARS-CoV-2 infection.

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The impact of hyperbaric oxygen therapy on late irradiation injury in oral microcirculation

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Abstract

Background

Late side effects of radiotherapy in patients with head and neck cancer (HNCPs) result in decreased tissue vascularity, a compromised healing capacity and spontaneous breakdown of tissue. The aim of this study was to examine the in vivo effect of hyperbaric oxygen therapy (HBOT) on the microcirculation in irradiated oral tissue.

Methods

Using a handheld microscope, the effect of HBOT on oral mucosal microcirculation parameters was measured in 34 previously irradiated HNCPs prior to HBOT and at 4 weeks and 6 months posttreatment.

Results

A significant increase in mean buccal vessel density and decrease in buccal vessel diameter was found 6 months after HBOT compared to baseline, 22 ± 11 versus 25 ± 7 cpll/mm2 (p < 0.05) and 20 ± 4 versus 16 ± 5 μm (p < 0.05), respectively.

Conclusion

Our results indicate that oral microcirculation histopathology associated with irradiation is able to respond to HBOT by redirecting oral microcirculation parameters towards values consistent with healthy tissue.

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Efficacy of the systemic co-administration of vitamin D3 in reversing the inhibitory effects of sodium alendronate on orthodontic tooth movement: A preliminary experimental animal study

alexandrossfakianakis shared this article with you from Inoreader

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Publication date: Available online 29 April 2022

Source: American Journal of Orthodontics and Dentofacial Orthopedics

Author(s): Mehrnaz Moradinejad, Marzie Yazdi, Seyed Ali Mard, Seyed Mohammad Razavi, Milad Shamohammadi, Fatemeh Shahsanaei, Vahid Rakhshan

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Verapamil down‐regulates iron uptake and up‐regulates divalent metal transporter 1 expression in H9C2 cardiomyocytes

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Abstract

Belgrade rats have a defect in divalent metal transport 1 (DMT1) with a reduced heart iron, indicating that DMT1 plays a physiological role in non-transferrin-bound iron (NTBI) uptake by cardiomyocytes. However, LVDCC (L-type voltage-dependent Ca2+ channel) blockers were recently demonstrated to significantly reduce NTBI uptake by cardiomyocytes, implying that LVDCC plays a dominant role in NTBI uptake by cardiomyocytes under iron-overloaded conditions. These findings led us to hypothesize that the LVDCC blocker-induced reduction in NTBI uptake might result not only from the inhibition of LVDCC-mediated NTBI uptake but also from the suppression of DMT1-mediated NTBI uptake. We therefore investigated the effects of the LVDCC blocker verapamil on NTBI uptake as well as DMT1 expression in H9C2 cells by the measurement of radio-labeled 55Fe(II), RT-PCR and western blot analysis. We demonstrated that verapamil induced a significant reduction in NTBI uptake by H9C2 cells, but also unexpectedly a remarkable increase rather than decrease in the expression of DMT1 mRNA and protein in H9C2 cells. Our findings imply that the verapamil-induced reduction in NTBI uptake by H9C2 cells is not associated with DMT1, and also indicate that verapamil stimulates rather than inhibits DMT1 expression and DMT1–mediated iron uptake by heart cells.

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Level Ib CTV delineation in nasopharyngeal carcinoma based on lymph node distribution and topographic anatomy

alexandrossfakianakis shared this article with you from Inoreader

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Publication date: Available online 29 April 2022

Source: Radiotherapy and Oncology

Author(s): Yue Zhao, Xiongfei Liao, Yiling Wang, Wanying Lan, Jing Ren, Ningjing Yang, Churong Li, Jingyi Lang, Shichuan Zhang

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Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

alexandrossfakianakis shared this article with you from Inoreader

Abstract

We aimed to assess longitudinal changes in clinical indexes of Covid-19 patients with mild pulmonary infection during 5 days of remdesivir therapy, and determine the effect of age and gender on remdesivir adverse effects (AE). Patients' clinical data including inflammatory markers, liver and renal function tests, and heart rate (HR) were extracted from medical records. Linear mixed model (LMM) was used to analyze longitudinal changes in patients' clinical indexes. Gender and age were inserted in LMM as covariates to find their correlation with AE and clinical indexes. Of 84 patients, 35 patients met our criteria for the study. There were significant increases in mean levels of white blood cell (WBC) (p=0.005), alanine aminotransferase (ALT) (p=0.001), aspartate aminotransferase (AST) (p=0.001), blood urea nitrogen (BUN) (p=0.001), and creatinine (p=0.006) while mean levels of erythrocyte sedimentation rate (ESR) (p=0.005), C-reactive protein (CRP) (p=0.001), alkaline phosphatase (ALP) (p=0.001), and potassium (p=0.003) decreased, significantly. Estimated glomerular filtration rate (eGFR) (p=0.001) and HR (p=0.001) showed a notable decline over the course of treatment. LMM analysis showed that mean changes in WBC (β=0.94, p=0.029), creatinine (β=0.12, p=0.020), and HR (β=6.47, p=0.008) were greater in males than females. Also, age of patients had a significant effect on the mean changes of WBC (β= -0.02, p=0.023), sodium (β= -0.06, p=0.010), BUN (β=0.23, p=0.001), and HR (β= -0.29, p=0.001). Despite no renal and liver dysfunction, Covid-19 patients with mild pulmonary infection may develop some remdesivir AE, and attributed side effects might be affected by gender and age of patients.

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HIV is associated with elevated FibroScan-AST (FAST) score

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Background & Aims
Whether HIV infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-AST (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort.
Approach
Vibration controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women living with HIV (WLWH) and 381 women living without HIV (WLWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score.
Results
Median age of WLWH and WLWOH was 51 years and 48 years, respectively. Most (90%) WLWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WLWH compared to WLWOH, 6.3% vs 1.8% (p=0.001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (p=0.002) and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (p<0.001). In analysis limited to WLWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score.
Conclusions
Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons living with HIV are warranted.
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Relative Vaccine Effectiveness of a SARS-CoV-2 mRNA Vaccine Booster Dose Against the Omicron Variant

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Background
The current SARS-CoV-2 vaccines may be less effective against the Omicron variant. With recent resurgence of SARS-CoV-2 cases, the role of booster doses of the vaccine needs to be highlighted.
Methods
Using a retrospective cohort study design emulating a target trial, we determined the relative effectiveness of a homologous booster dose of a SARS-CoV-2 mRNA vaccine compared with primary series alone in preventing infection, hospitalization, a nd intensive care unit (ICU) admission, and death in the Department of Veterans Affairs healthcare system in the US. Among infection-free survivors who received two doses of an mRNA vaccine prior to April 30, 2021, we identified those who received a booster between September 22 and December 25, 2021 and 1:1 matched individuals who did not receive a booster.
Results
Among 2,384,272 previously uninfected persons with two doses of an mRNA vaccine by April 30, 2021, we identified 462,950 booster recipients between September 22 and December 25, 2021 who were matched 1:1 with non-booster recipients. RVE (95% CI) was 19% (17-22%) for confirmed infection, 52% (46-57%) for hospitalization, and 83% (65-92%) for ICU admission or death. Recipients of the mRNA-1273 vaccine had a lower cumulative incidence of infections and hospitalizations compared with BNT-162b2 vaccine (log-rank p-value <0.001 for both comparisons).
Conclusion
While the RVE of SARS-CoV-2 mRNA booster vacci ne dose in preventing infection against the Omicron variant is low, the RVE is substantial in preventing hospitalization and high in preventing the most severe/critical disease.
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Gratitude, relatedness needs satisfaction, and negative psychological outcomes during the COVID‐19 pandemic: A short‐term longitudinal study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objectives

Although gratitude relates to coronavirus disease 2019 (COVID-19) well-being outcomes in the United States, more evidence is needed to understand how this psychological strength reciprocally relates to mental health during this pandemic. This study examines the association of gratitude with stress, anxiety, and depression among undergraduate students in the United States via a longitudinal design.

Methods

An online survey was administered to 643 undergraduate students in a public university located in the southeastern region of the United States. There was a 1-month interval between the first and second waves of data collection.

Results

Cross-lagged panel structural equation modeling showed that whereas gratitude positively predicted subsequent relatedness needs satisfaction, it negatively predicted later stress, anxiety, and depression. Relatedness needs satisfaction was reciprocally linked to subsequent gratitude.

Conclusion

Results suggest that gratitude might serve as a protective psychological resource against the detrimental mental health impacts of the COVID-19 pandemic.

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Investigating the efficacy of attentional bias modification on individuals with spider phobia through the emotional attention network test

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objectives

This study aimed to investigate the attention network function of spider phobics before and after attentional bias modification (ABM) through conduction of an emotional attention network test (eANT).

Methods

Scores from an eANT, an approach–avoidance task, and various scales were used to examine the training effect of a single ABM session among participants (30 individuals with spider phobia and 30 controls).

Results

At baseline, alertness scores in response to spider images were higher in the phobia group than in the control group ( = 51.81 vs. 30.35 ms). After ABM, this score decreased in the phobia group, indicating their lower susceptibility to distraction by images of spiders. However, ABM training did not considerably alleviate their fear of and avoidance behavior toward spiders.

Conclusion

This study elucidates the (1) vigilance–avoidance pattern among individuals with spider phobia when encountering spider-related stimuli and (2) change in underlying attentional mechanisms after ABM training.

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Incidence, etiology, risk factors and outcomes of pre‐engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

With increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT.

Materials and methods

This is a retrospective study of 284 patients who underwent first allo-HCT and 37 patients after the second allo-HCT at the National Research Center for Hematology in Moscow, Russia, from January 2018 till September 2021.

Results

Cumulative incidence of pre-engraftment BSI was 29.9% after the first allo-HCT and 35.1% after the second (p = 0,805). Median time to the first BSI was 9 days (range 0–61 days) after the first and 16 days (range 1–28 days) after the second allo-HCT (p = 0.014). A total of 113 pathogens were isolated during 94 BSI episodes after the first allo-HCT (gram-negative bacteria 52.2%; gram-positive bacteria 47.7%). Fourteen pathogens were isolated during 14 BSI episodes after the second allo-HCT (gram-negative bacteria 50.0%; gram-positive bacteria 50.0%). The only significant difference was found in the rate of carbapenem-resistant gram-negative bacteria, which was higher after the second allo-HCT compared to the first (57.1% vs. 13.6%; p = 0.048).

Mismatched unrelated donor (HR 3.01; 95% CI:1.62-5.60; p<0.0001) and haploidentical donor transplantations (HR 1.84; 95% CI:1.02-3.33; p = 0.042) were the only independent risk factors associated with the higher risk of pre-engraftment BSI.

Overall 30-day survival after all BSI episodes was 94.4%,. Survival was lower after BSI during the second allo-HCT compared to the first (71.4% vs. 97.9%; p<0,0001), particularly after BSI caused by carbapenem-resistant gram-negative bacteria (25.0% vs. 100.0%; p = 0.0023). Non-relapse mortality rate at day +60 was 4.0%, and the risk was highly associated with primary graft failure (HR 9.62; 95% CI: 1.33-71.43), second allo-HCT (HR 6.80; 95% CI: 1.36-34.48), and pre-engraftment BSI caused by carbapenem-resistant gram-negative bacteria (HR 32.11; 95% CI: 4.91-210.15).

Conclusions

Pre-engraftment BSI is still a common complication after allo-HCT, particularly after mismatched unrelated and haploidentical donor transplantations. BSI incidence was slightly higher after the second allo-HCT with significantly higher rate of carbapenem-resistant BSI. Although pre-engraftment BSI would generally follow benign clinical course, survival was dramatically lower during the second allo-HCT especially after carbapenem-resistant BSI.

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Clinical evaluation of the GSD NovaPrime® SARS-CoV-2 RTq-PCR assay

alexandrossfakianakis shared this article with you from Inoreader

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Publication date: Available online 3 May 2022

Source: Diagnostic Microbiology and Infectious Disease

Author(s): Marie Tré-Hardy, Sébastien Piteüs, Ingrid Beukinga, Laurent Blairon

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