SARS‐CoV‐2 ORF10 antagonizes STING‐dependent interferon activation and autophagy

alexandrossfakianakis shared this article with you from Inoreader SARS‐CoV‐2 ORF10 antagonizes STING‐dependent interferon activation and autophagy via Journal of Medical Virology Abstract A characteristic feature of COVID-19, the disease caused by SARS-CoV-2 infection, is the dysregulated immune response with impaired type I and III interferon (IFN) expression and an overwhelming inflammatory cytokine storm. RIG-I-like receptors (RLRs) and cGAS-STING signaling pathways are responsible for sensing viral infection and inducing IFN production to combat invading viruses. Multiple proteins of SARS-CoV-2 have been reported to modulate the RLR signaling pathways to achieve immune evasion. Although SARS-CoV-2 infection also activates the cGAS-STING signaling by stimulating micronuclei formation during the process of syncytia, whether SARS-CoV-2 modulates the cGAS-STING pathway requires further investigation. Here, we screened 29 SARS-CoV-2-encoded viral proteins to explore the viral proteins that affect the cGAS-STING signaling pathway and found that SARS-CoV-2 ORF10 targets STING to antagonize IFN activation. Overexpression of ORF10 inhibits cGAS-ST ING-induced IRF3 phosphorylation, translocation, and subsequent IFN induction. Mechanistically, ORF10 interacts with STING, attenuates the STING-TBK1 association, and impairs STING oligomerization and aggregation and STING-mediated autophagy; ORF10 also prevents the endoplasmic reticulum (ER)-to-Golgi trafficking of STING by anchoring STING in the ER. Taken together, these findings suggest that SARS-CoV-2 ORF10 impairs the cGAS-STING signaling by blocking the translocation of STING and the interaction between STING and TBK1 to antagonize innate antiviral immunity. This article is protected by copyright. All rights reserved. View on Web

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Voice Therapy Improves Acoustic and Auditory‐Perceptual Outcomes in Children

alexandrossfakianakis shared this article with you from Inoreader Voice Therapy Improves Acoustic and Auditory‐Perceptual Outcomes in Children via The Laryngoscope This study examined the effects of voice therapy in 129 children diagnosed with benign vocal fold lesions. Significant improvements were observed in auditory-perceptual assessments, jitter, Noise-to-Harmonic Ratio (NHR), and cepstral peak prominence (CPP) on sustained vowels, as well as CPP and Low-to-High Ratio (LHR) on connected speech. CPP effectively quantified voice therapy gains and allowed for analysis of connected speech. These findings demonstrate the value of CPP as a tool in assessing pediatric voice therapy outcomes and support the efficacy of voice therapy for children presenting with benign vocal fold lesions. Purpose This study employed acoustic measures as well as auditory-perceptual assessments to examine the effects of voice therapy in children presenting with benign vocal fold lesions. Methods A retrospective, observational cohort design was employed. Sustained vowels produced by 129 children diagnosed with benign vocal fold lesions were analyzed, as well as connected speech samples produced by 47 children. Treatment outcome measures included Consensus of Auditory-Perceptual Evaluation of Voice (CAPE-V), jitter, shimmer, Noise-to-Harmonic Ratio (NHR), cepstral peak prominence (CPP), and Low-to-High Ratio (LHR) on sustained vowels, and CPP and LHR on connected speech. Results Following voice therapy, significant improvements in CAPE-V ratings (p < 0.001) were observed. Additionally, jitter (p = 0.041), NHR (p = 0.019), and CPP (p < 0.01) on sustained vowels, and CPP (p = 0.002), and LHR (p = 0.008) on connected speech significantly improved following voice therapy. CPP increased with age in males but did not change in females. CAPE-V ratings and perturbation measures indicated that dysphonia was more severe in younger children pre and post-therapy. Conclusions Auditory-perceptual and acoustic measures demonstrated improved voice quality following voice therapy in children with dysphonia. CPP effectively quantified voice therapy gains and allowed for analysis of connected speech, in addition to sustained vowels. These findings demonstrate the value of CPP as a tool in assessing therapy outcomes and support the efficacy of voice therapy for children presenting with vocal fold lesions. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Hypothyroidism After Using Superior Thyroid Artery as A Recipient Artery

alexandrossfakianakis shared this article with you from Inoreader Hypothyroidism After Using Superior Thyroid Artery as A Recipient Artery via The Laryngoscope The aim of this study was to evaluate whether the use of the superior thyroid artery (SThA) as a recipient vessel affect thyroid dysfunction in patients undergoing TPLE combined with hemithyroidectomy. Our study revealed there was no significant difference in the postoperative hypothyroidism between patients with SThA used and not. We suggest that even after hemithyroidectomy, with inferior thyroid arteries are preserved, the SThA can be used as a recipient vessel. Objective Superior thyroid artery (SThA) is a common recipient artery in free tissue transfer even after total pharyngolaryngoesophagectomy (TPLE) with hemithyroidectomy. The aim of this study was to evaluate whether the use of SThA as a recipient vessel affect thyroid function in patients undergoing TPLE with hemithyroidectomy. Methods From 2011 to 2020, 91 patients who underwent free jejunum transfer after TPLE with hemithyroidectomy were divided into two groups. In Group1 (n = 47), the contralateral SThA was used for the anastomosis. In Group2 (n = 44), other vessels were used. Retrospective chart review was performed comparing postoperative thyroid function between two groups. Results In group1, 17 patients presented hypothyroidism, 21 presented latent hypothyroidism and 9 presented no thyroid dysfunction comparing 15, 19, and 10 respectively in group 2. There were no significant differences between the two groups. Conclusion Even after hemithyroidectomy, with inferior thyroid arteries are preserved, the SThA can be used as a recipient vessel. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Proteomic analysis of infected root canals with apical periodontitis in patients with type 2 diabetes mellitus: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader Proteomic analysis of infected root canals with apical periodontitis in patients with type 2 diabetes mellitus: a cross‐sectional study via International Endodontic Journal Abstract Aim This study aimed to quantitatively and qualitatively determine the proteomic profile of apical periodontitis (AP) in Type 2 Diabetes Mellitus (T2DM) patients in comparison to systemically non-compromised patients, and to correlate the protein expression of both groups with their biological functions. Methodology The sample consisted of 18 patients with asymptomatic AP divided into two groups according to the presence of T2DM: diabetic group - patients with T2DM (n = 9) and control group - systemically healthy patients (n = 9). After sample collection, the root canal samples were prepared for proteomic analysis using reverse-phase liquid chromatography mass spectrometry. Label-free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in protein expression between groups were calculated using t-test (p < 0.05). Biological functions were analyzed using the Homo sapiens UniProt database. Results A total of 727 human proteins were identified in all samples. Among them, 124 proteins common to both groups were quantified, out of which 65 proteins from the diabetic group showed significant differences compared with the control: 43 up-regulated (p < 0.05) and 22 down-regulated (p < 0.05) proteins. No significant differences in protein expression were seen for the remaining 59 proteins (p > 0.05). Most proteins with differences in expression were related to immune/inflammatory response. Neutrophil gelatinase-associated lipocalin, Plastin-2, Lactotransferrin, and 13 isoforms of immunoglobulins were up-regulated. In contrast, Protein S100-A8, Protein S100-A9, Histone H2B, Neutrophil defensin 1, Neutrophil defensin 3, and Prolactin-inducible protein were down-regulated. Conclusions Quantitative differences were demonstrated in the expression of proteins common to diabetic and control groups, mainly related to immune response, oxidative stress, apoptosis, and proteolysis. These findings revealed biological pathways that provide the basis to support clinical findings on the relationship between AP and T2DM. View on Web

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The impact of midazolam used in cataract surgery sedation on frontal QRS‐T angle

alexandrossfakianakis shared this article with you from Inoreader The impact of midazolam used in cataract surgery sedation on frontal QRS‐T angle via Journal of Clinical Pharmacy and Therapeutics Only 177 patients who underwent elective cataract surgery were included in the study. Surgery in patients was planned with at least moderate sedation. This target was determined to be a 5–6 on the Ramsay Sedation Scale. Before the procedure, a venous route from the forearm was used to administer midazolam for sedation. The sedative effect was evaluated 2–3 minutes after a 0.05 mg/kg dose of midazolam was given. Sedation was assessed again by giving 0.5 mg every 2–3 minutes until the desired level of sedation was achieved. Electrocardiographic recordings were taken just before and within the first 5 minutes after surgery. QT, QTc intervals, Tp-e interval, Tp-e/QT, Tp-e/QTc and frontal QRS-T angle measurements got from ECG recordings. There was no significant difference between all values measured before and after the procedure. As a result, providing sedanalgesia using midazolam does not cause any change in ECG markers showing ventricular repolarization. Th erefore, the use of midazolam is safe for developing cardiac arrhythmias. Abstract What is known and objective Midazolam is one of the most commonly used drugs in procedures requiring sedoanalgesia. It affects the myocardium's ventricular depolarization and repolarization. Previous studies examining the arrhythmogenic effects of midazolam yielded conclusive results. These studies are based on QT and Tp -e distances. The frontal QRS-T angle (f-[QRS-T]a) is a new electro cardiac parameter that shows the heterogeneity of ventricular electrical activity. This study aims to examine the effect of midazolam on f-(QRS- T)a and other depolarization-repolarization parameters in patients who have had cataract surgery. Methods The study included 177 patients administered midazolam as a sedoanalgesia during cataract surgery. The sedative effect was evaluated 2–3 minutes after a 0.05 mg/kg dose of midazolam was given. Sedation was assessed again by giving 0.5 mg every 2–3 minutes until the desired level of sedation was achieved. 12-lead electrocardiogram (ECG) recordings of all patients were taken just before and immediately after surgery. ECGs were used to calculate the QT interval, QTc interval, Tp -e interval, Tp -e/QT, Tp -e/ QTc ratios and f-(QRS-T)a. Results and discussion After cataract surgery, f-(QRS-T)a was unchanged compared to presurgery (29.14 ± 4.52 vs. 29.18 ± 5.39, p = 0.852). In addition, no significant change in QT(351.32 ± 21.98 vs. 351.94 ± 22.44, p = 0.091), QTc (384.05 ± 24.52 vs. 385.19 ± 26.12, p = 0.819), Tp -e interval (93.12 ± 9.60 vs. 94.44 ± 8.82, p = 0.179) and Tp -e/QT (0.27 ± 0.02 vs. 0.28 ± 0.03, p = 0.664), Tp -e/ QTc ratios (0.28 ± 0.02 vs. 0.29 ± 0.03, p = 0.655) was observed after surgery when compared to presurgery values. Significant ventricular and supraventricular arrhythmias were not observed in any patient during the operation. What is new and conclusion Midazolam did not affect f -(QRS-T) with classical repolarization parameters in patients who underwent cataract surgery, according to this study. Midazolam has been found to be safe for the heart in sedoanalgesia. These results show that sedation with midazolam can be performed without electrocardiogram monitoring. View on Web

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Comparison of transfusion reactions in children and adults: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Comparison of transfusion reactions in children and adults: A systematic review and meta‐analysis via Pediatric Blood & Cancer Abstract Background There are no international standards or normalizations for diagnosing and treating complications from blood transfusions. We comprehensively compared the incidence of adverse blood transfusions in children and adults. Methods Available literature on blood transfusion adverse reactions in children and adults prior to November 27, 2021 was collected from several electronic databases. This meta-analysis was performed using Revman 5.2 and Stata 15.1. Results The incidence of transfusion reactions is higher in children than in adults. Children transfused with red blood cells and platelets exhibited a higher incidence of transfusion reaction than that of adults. Moreover, the incidence of allergic and febrile non-hemolytic transfusion reactions was significantly higher in children than in adults. The incidence of some rare transfusion reactions was also significantly higher in children than in adults. Conclusion The incidence of transfusion reactions in children and adults is varied. Guidelines for children are necessary. View on Web

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Safety and value of pre‐transplant antibiotic allergy delabeling in a quaternary transplant center

alexandrossfakianakis shared this article with you from Inoreader Safety and value of pre‐transplant antibiotic allergy delabeling in a quaternary transplant center via Transplant Infectious Disease Abstract Background Self-reported antibiotic allergies, also known as antibiotic allergy labels, are common and may lead to worse patient outcomes. Within immunocompromised patients, antibiotic allergy labels can lead to inappropriate use of antimicrobials and may limit options for prophylactic and therapeutic options in the post-transplant period. While antibiotic allergy delabeling is considered an important aspect of antibiotic stewardship protocols, evidence and awareness of its application in transplant recipients is limited. Methods We describe our experience with an antibiotic allergy delabeling intervention in the pre-transplant evaluation period and its impact on post-transplant antimicrobial utilization. This was a retrospective analysis of patients with an antibiotic allergy label who underwent evaluation for solid organ or stem cell transplantation between 2015–2020. Patients included in this analysis were those who completed pre-transplant antibiotic allergy delabeling through our Drug Allergy Clinic and were retained in care for six months after transplant. Results Twenty-six of 27 patients underwent pre-transplant antibiotic allergy delabeling and safely received the delabeled antibiotic post-transplant. There were no reported side effects to the delabeled antibiotic within 6 months post-transplant. Specific examination of sulfonamide (sulfa)-antibiotic delabeling showed cost savings of $254 to $2,910 per patient in the post-transplant period compared to the use of alternative antibiotics for prophylaxis protocol. Conclusion Antibiotic allergy delabeling prior to transplant is safe, is of high value, and should be considered in the pre-transplant evaluation period. More resources are needed for the development of delabeling guidelines and support for broad implementation of pre-transplant antibiotic allergy delabeling programs. This article is protected by copyright. All rights reserved View on Web

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Evaluation of soft tissue and labial plate of bone stability with immediate implant in direct contact versus gap with socket shield: A randomized clinical trial with 1 year follow‐up

alexandrossfakianakis shared this article with you from Inoreader Evaluation of soft tissue and labial plate of bone stability with immediate implant in direct contact versus gap with socket shield: A randomized clinical trial with 1 year follow‐up via Clinical Implant Dentistry and Related Research Abstract Objective In the anterior region, the resorption of the buccal plate of bone after tooth extraction leads to contraction of the overlying soft tissues, resulting in an esthetic problem. In the socket shield technique, the buccal root section of the tooth is maintained, to preserve the buccal bone for immediate implant placement. The aim of this randomized clinical trial was to investigate the effect of leaving a gap or not between implant and retained root fragment on bone dimensions and soft tissue esthetics. Methods This was a two armed parallel group randomized clinical trial with allocation ratio 1:1. Patients were eligible in case they needed immediate implant replacing teeth in esthetic zone with sufficient buccal bone support. CBCT was performed immediately after the intervention and 12 months later. Results Forty six patients (26 females and 20 males) were enrolled in the study with 23 of them placed in contact with shield and 23 were placed palatal leaving a gap to graft with a xenograft. After 12 months, excellent soft tissue stability was reported (mean pink esthetic score at placement group A: 12.00 ± 1.60 after 12 months 12.90 ± 1.69, group B 12.62 ± 2.07 and after 12 months 12.38 ± 2.20) Using both surgical techniques. Radiographic crestal bone level changes mean for group A was −0.26 ± 0.52 and for group B -0.34 ± 0.31. There was a strong positive correlation between clinical and radiographic bone width values which was statistically significant (r = 0.782, p < 0.001). Width and thickness of keratinized gingiva showed no significant difference between values measured in both groups. Nonsignificant difference between studied groups according to the labial plate of bone clinical and radiographic changes after i mmediate implantation. Conclusion Within the limitations of this study, the present data seem to support that the clinical outcome of the socket shield technique with immediate implant placement placed in contact or leaving a gap gave excellent esthetic results. View on Web

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Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume

alexandrossfakianakis shared this article with you from Inoreader Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume via Brain Pathology The complex formation of post-ICH brain edema. Abstract We aimed to analyze the inflammatory and oxidative stress (OS) markers after intracerebral hemorrhage (ICH) and their temporal changes, interaction effects, and prognostic values as biomarkers for the prediction of the edema volume. Our prospective, longitudinal study included a cohort group of 73 conservatively treated patients with ICH, without hematoma expansion or intraventricular bleeding, which were initialized with the same treatment and provided with the same in-hospital care during the disease course. Study procedures included multilevel comprehensive analyses of clinical and neuroimaging data, aligned with the exploration of 19 inflammatory and five OS markers. White blood cells (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophilia, and lymphopenia peaked 3 days post-ICH, and they showed much stronger correlations with clinical and neuroimaging variables, when compared to the admission values. An intricate interplay among inflammatory (WBC , CRP, neutrophils, neutrophil-to-lymphocyte ratio [NLR], interleukin (IL)-6, and IL-10) and OS mechanisms (catalase activity and advanced oxidation protein products [AOPP]) was detected operating 3-days post-ICH, being assessed as relevant for prediction of the edema. The overall results suggested complex pathology of formation of post-ICH edema, via: (A) Not additive, but statistically significant synergistic interactions between CRP-ESR, neutrophils-CRP, and neutrophils-IL-6 as drivers for the edema formation; (B) Significant antagonistic effect of high protein oxidation on the CRP-edema dependence, suggesting a mechanism of potential OS-CRP negative feedback loop and redox inactivation of CRP. The final multiple regression model separated the third-day variables NLR, CRP × AOPP, and WBC, as significant prognostic biomarkers for the prediction of the edema volume, with NLR being associated with the highest effect size. Our developed mathematical equation with 3D modeling for prediction and quantification of the edema volume might be beneficial for taking timely adequate strategies for prevention of delayed neurological deteriorations. View on Web

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