Safety and Immunogenicity of a Recombinant Receptor Binding Domain‐Based Protein Subunit Vaccine (Noora Vaccine™) Against COVID‐19 in Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Phase 1 Trial

alexandrossfakianakis shared this article with you from Inoreader Safety and Immunogenicity of a Recombinant Receptor Binding Domain‐Based Protein Subunit Vaccine (Noora Vaccine™) Against COVID‐19 in Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Phase 1 Trial via Journal of Medical Virology Abstract The development of a safe and effective vaccine is essential to protect populations against COVID-19. There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in adults. This phase 1 trial is a randomized, double-blind, placebo-controlled study to evaluate the safety and immunogenicity of the recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this st udy. Secondary outcomes including the humoral and cellular immunity (including anti-RBD IgG antibody and neutralizing antibody) were measured on days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti-RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, P<0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this ph ase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial. This article is protected by copyright. All rights reserved. View on Web

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Elevated preradiotherapy serum lactate dehydrogenase predicts distant metastasis for lymphoepithelial carcinoma of major salivary gland following postoperative radiotherapy

alexandrossfakianakis shared this article with you from Inoreader Elevated preradiotherapy serum lactate dehydrogenase predicts distant metastasis for lymphoepithelial carcinoma of major salivary gland following postoperative radiotherapy via Head & Neck Abstract Background To evaluate the predicting factors associated with distant metastasis (DM) for lymphoepithelial carcinoma of salivary gland (LECSG) following postoperative radiotherapy (PORT). Methods We retrospectively collected 160 eligible patients from two cancer institutions. The DM rate was evaluated using competing risk method. Results The median follow-up time was 65.6 months. Elevated preradiotherapy serum LDH (ratio >0.5) (p = 0.006) and N classification (N2-3) (p = 0.001) were independently associated with DM for the LECSG. After the risk stratification, the high-risk subgroup was defined as the patients presented higher risk score (score >0), whereas 5-year cumulative incidence of DM in the high- and low-risk group was 30.9% and 6.0%, respectively (p < 0.001). Moreover, a significantly worse overall survival (OS) was observed in the high-risk patients compared with the low-risk subgroup (5-year OS: 83.9% vs. 97.8%, p = 0.006). Conclusion Elevated preradiotherapy serum LDH could serve as a predictive factor for DM in the LECSG following PORT. View on Web

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Curcumin reduces inflammation in rat apical periodontitis

alexandrossfakianakis shared this article with you from Inoreader Curcumin reduces inflammation in rat apical periodontitis via International Endodontic Journal Abstract Aim To evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP). Methodology Forty male Wistar rats weighing 250-280g each, age 2.5 months, were distributed into four groups (n=10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP), and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a program specific for micro-CT. The jaws were processed for analysis of the inflammatory process using Haemotoxylin and Eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6, and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyze the resorptive process on the bone surface of periapical area. Kruskal–Wallis with Dunn's test was performed for nonparametric data, and ANOVA with Tukey's test for parametric data, p < .05. Results Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6, and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05). Conclusions Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development. View on Web

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Risk Factors for Recurrence of Peritonsillar Abscess

alexandrossfakianakis shared this article with you from Inoreader Risk Factors for Recurrence of Peritonsillar Abscess via The Laryngoscope Objectives This study aimed to investigate the risk factors associated with peritonsillar abscess (PTA) recurrence in adult patients. Methods This retrospective cohort study used a nationwide insurance claims database in Japan. Adult patients (aged ≥ 20 years) who received intravenous antibiotics or surgical therapy within 5 days of their first PTA diagnosis were included. Multivariable Cox proportional modeling was used to investigate the risk factors for PTA recurrence using the variables: age, sex, comorbidities, tobacco use, history of recurrent tonsillitis, duration of intravenous antibiotics, and surgical therapy for PTA. Results This study included 12,012 patients (8784 men, 73.1%). Of them, 1358 (11.3%) experienced PTA recurrence. An age ≥40 years and treatment with intravenous antibiotics for 3 days or more were associated with a lower risk of PTA recurrence (aged ≥ 40 years: adjusted hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.62–0.78, treated with intravenous antibiotics for 3 days or more: adjusted HR: 0.85; 95% CI: 0.76–0.96). Patients with a history of recurrent tonsillitis were associated with a higher risk of recurrence (adjusted HR: 1.79; 95% CI: 1.47–2.19). Conclusion A median age of 20–39 years, a history of recurrent tonsillitis, and less than 3 days of intravenous antibiotic therapy may be risk factors for PTA recurrence among adult patients. Further studies exploring more detailed clinical data are necessary to confirm the risk factors for PTA recurrence. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Infants Receiving Very Early ART Have High CD4 Counts in the First Year of Life

alexandrossfakianakis shared this article with you from Inoreader Infants Receiving Very Early ART Have High CD4 Counts in the First Year of Life via Clinical Infectious Diseases Advance Access ABSTRACT We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At Weeks 24 and 48, ≥80% had CD4 ≥ 1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. View on Web

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Coinfections in hospitalized patients with severe fever with thrombocytopenia syndrome: a retrospective study

alexandrossfakianakis shared this article with you from Inoreader Coinfections in hospitalized patients with severe fever with thrombocytopenia syndrome: a retrospective study via Journal of Medical Virology Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotics therapy. Study design A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. Results A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospital were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in respiratory tract and bloodstream were associated with a higher risk of death than that in urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. Conclusion The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS. This article is protected by copyright. All rights reserved. View on Web

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Fra‐1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury

alexandrossfakianakis shared this article with you from Inoreader Fra‐1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury via Brain Pathology Schematic illustration depicting the mechanism by which Fra-1-mediated S100A8/TLR4/NF-κB and ERK signaling in the regulation of apoptosis and neuroinflammation during spinal I/R. Abstract Spinal cord ischemia/reperfusion injury (SCII) is a severe complication driven by apoptosis and neuroinflammation. An increase in the expression of c-Fos, a member of the AP-1 family, is known as a neuronal activation marker in SCII. The AP-1 family is composed of Jun, Fos, and is associated with the regulation of cytokines expression and apoptosis. Fra-1 is a member of the Fos family, however, the contribution of Fra-1 to SCII is still unclear. In our study, Fra-1 was highly upregulated especially in neurons and microglia and promoted apoptosis by changing the expression of Bax/Bcl-2 after SCII. Furthermore, we found that Fra-1 directly regulated the transcription expression of S100A8. We demonstrated that knockdown of Fra-1 alleviated S100A8 mediated neuronal apoptosis and inflammatory factor release, thus improved motor function after SCII. Interestingly, we showed that administration of TAK-242, the TLR4 inhibitor, to the ischemia/reperfusion (I/R) injury induced rats suppress ed the activation of the ERK and NF-κB pathways, and further reduced Fra-1 expression. In conclusion, we found that Fra-1-targeted S100A8 was expressed the upstream of Fra-1, and the Fra-1/S100A8 interaction formed a feedback loop in the signaling pathways activated by SCII. View on Web

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