Effect of sintering on the translucency of CAD‐CAM lithium disilicate restorations: a comparative in vitro study

alexandrossfakianakis shared this article with you from Inoreader Effect of sintering on the translucency of CAD‐CAM lithium disilicate restorations: a comparative in vitro study via Journal of Prosthodontics Abstract Purpose The available independent data on the translucency of novel pre and fully sintered chair-side computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate are limited. This comparative in vitro study evaluated the translucency degree of pre and fully sintered chairside CAD-CAM lithium disilicate crowns after optional, required, and additional firing processes. Materials and Methods One hundred and five maxillary left central incisor crowns manufactured by three different CAD-CAM lithium disilicate brands shade A1 were assigned into 7 groups as follows (n = 15): (1) n!ce Straumann without sintering; (2) n!ce Straumann with one additional sintering process; (3) n!ce Straumann with two additional sintering processes; (4) Amber Mill with one sintering process; (5) Amber Mill with two sintering processes; (6) IPS e.max CAD with one sintering process; (7) IPS e.max CAD with two sintering processes. The translucency of all crowns was evaluated with a color imaging spectrophotometer. All statistical analyses were performed using statistical software. A standard level of significance was set at α < 0.05. Results All the milled crowns presented different degrees of translucency, and additional sintering processes altered it. IPS E.max CAD with two (4.33 ± 0.26) and one (4.01 ± 0.15) sintering processes displayed the highest translucency, whereas n!ce Straumann with no sintering process provided the lowest value (2.82 ± 0.16). Conclusions The translucency of chairside lithium disilicate single-unit full-coverage restorations manufactured with subtractive technology was significantly influenced by the brand and the number of sintering processes. The traditional presintered IPS e.max CAD and the fully crystallized glass-ceramic n!ce Straumann considerably increased the translucency after one additional firing process, whereas Amber Mill decreased its translucency. This article is protected by copyright. All rights reserved View on Web

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Nirmatrelvir‐ritonavir for the treatment of COVID‐19 patients: a systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Nirmatrelvir‐ritonavir for the treatment of COVID‐19 patients: a systematic review and meta‐analysis via Journal of Medical Virology Abstract Nirmatrelvir-ritonavir (Paxlovid™) is an oral antiviral that has been approved for the treatment of mild-to-moderate COVID-19. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of nirmatrelvir-ritonavir in COVID-19 patients. Various databases including PubMed, the Cochrane Library, medRxiv and Embase were searched from inception till 10 October 2022 and results from 12 studies (two randomized controlled trials (RCTs) and 10 observational studies) were pooled using a random-effects model with risk ratio (RR) as the effect measure. Nirmatrelvir-ritonavir reduced the risk of mortality (RR 0.24; 95% CI:0.15–0.37, I2=48%; moderate certainty) and hospitalization (RR 0.41; 95% CI:0.29–0.59, I2=90%; low certainty) in both patients with or without previous immunity to SARS-CoV-2 without an increased risk of adverse events. Our study provides encouraging evidence for nirmatrelvir-ritonavir as a safe and efficacious agent for COVID-19 but lar ge-scale RCTs are needed to confirm these findings. This article is protected by copyright. All rights reserved. View on Web

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Outcomes of KTP Laser Ablation in Glottic Neoplasms: A Systematic Review and Meta‐Analysis

alexandrossfakianakis shared this article with you from Inoreader Outcomes of KTP Laser Ablation in Glottic Neoplasms: A Systematic Review and Meta‐Analysis via The Laryngoscope The aim of our review is to evaluate the safety and efficiency of transoral laser microsurgery (TLM) with potassium-titanyl-phosphate (KTP) laser ablation for glottic neoplasms. Eight studies were included. After an average follow-up of 3.3 years, the overall survival and disease-free survival for patients who underwent KTP. KTP is a safe and effective method for treating patients with early glottic neoplasms. Objectives To evaluate the safety and clinical effectiveness of transoral laser microsurgery (TLM) with potassium-titanyl-phosphate (KTP) laser ablation for glottic neoplasms. Data Source MEDLINE via PubMed, SCOPUS, Web of Science, and Cochrane Library. Review Methods A systematic review and meta-analysis of studies assessing the safety and efficacy of KTP laser therapy in patients with early-stage glottic neoplasms. Results Eight studies were included. After an average follow-up of 3.3 years, the overall survival and disease-free survival for patients who underwent KTP were 90.7% (95% CI 85%–96.5%) and 98.5% (95% CI 97.3%–99.8%), respectively. In the single-arm meta-analysis, the pooled estimate of recurrence was 7.7% (95% CI 3.4%–12%). The overall voice handicap index (VHI) estimate attributed to KTP in the single-arm meta-analysis was 6.76 (95% CI [3.05, 10.48]) and 5.21 (95% CI [2.86, 7.56]) within 6 months and after a one-year follow-up, respectively. Conclusion KTP laser ablation is a safe and effective method for treating patients with early glottic neoplasms. Laryngoscope, 2023 View on Web

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Upregulation of PD‐L1 by SARS‐CoV‐2 promotes immune evasion

alexandrossfakianakis shared this article with you from Inoreader Upregulation of PD‐L1 by SARS‐CoV‐2 promotes immune evasion via Journal of Medical Virology Abstract Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T cell sequestration, cytokine storm and mortality. However, it remains largely unknown how SARS-CoV-2 induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network (TO-GCN) approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated NF-κB and IRF1 pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 ChIP-sequencing. Cross-referencing our transcriptomic and epigenomic datasets revealed that coupling NF-κB and IRF1 pathways mediate PD-L1 immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an earl y stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity. This article is protected by copyright. All rights reserved. View on Web

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Single‐cell transcriptomics dissects epithelial heterogeneity in HPV+ cervical adenocarcinoma

alexandrossfakianakis shared this article with you from Inoreader Single‐cell transcriptomics dissects epithelial heterogeneity in HPV+ cervical adenocarcinoma via Journal of Medical Virology Abstract The intra- and inter-tumoral heterogeneity of epithelial cells in human papillomavirus (HPV)+ cervical adenocarcinoma (CEAD) remains largely unknown. To investigate this issue, we performed single-cell RNA sequencing on 19,229 epithelial cells sorted from three tumor samples of three patients with HPV+ CEAD. Six epithelial subclusters (Epi1 to Epi6) were identified that showed distinct gene expression. Among these, Epi1 and Epi4 had apparent tumor hallmarks and metabolic activities. Epi1 was highly enriched in hallmarks of hypoxia, IL2/STAT5 signaling, retinol metabolism, glycolysis, and arachidonic acid metabolism, while Epi4 was highly enriched in hallmarks of G2M checkpoint, E2F targets, DNA repair, PI3K/AKT/MTOR signaling, glycolysis, fatty acid degradation, TCA cycle, and glutathione metabolism. We also investigated inter-tumoral epithelial heterogeneity and found that Patient 1 was highly enriched for KRAS signaling and angiogenesis, while Patient 2 was highly enriched for epithelial-mesenchymal transition and TGF-β signaling, and Patient 3 was highly enriched for hypoxia, DNA repair, G2M checkpoint, and E2F targets. Using single-cell RNA sequencing, we revealed the intra- and inter-tumoral heterogeneity of epithelial cells in HPV+ CEAD, providing insights into the importance of personalized treatment for patients with HPV+ CEAD. This article is protected by copyright. All rights reserved. View on Web

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Effectiveness and pharmacokinetic exposures of first-line drugs used to treat drug-susceptible tuberculosis in children: a systematic review and meta-analysis

alexandrossfakianakis shared this article with you from Inoreader Effectiveness and pharmacokinetic exposures of first-line drugs used to treat drug-susceptible tuberculosis in children: a systematic review and meta-analysis via Clinical Infectious Diseases Advance Access Abstract Background Optimal doses of first line drugs for drug-susceptible tuberculosis (DS-TB) treatment in children and young adolescents remain uncertain. We aimed to determine if children treated using WHO-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic exposures. Methods Titles, abstracts, and full-text articles were screened. We searched Pubmed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children <18 years, being treated for DS-TB with rifampicin, pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO, CRD42021274222. Results Of 304 studies identified, 46 studies were eligible for full-text review and 12 and 18 articles were included for the efficacy and pharmacokinetic analysis, respectively. Of 1,830 children in cluded in the efficacy analysis, 82% had favourable outcomes (range 25%-95%). At WHO-recommended doses, exposures to rifampicin, pyrazinamide, and ethambutol were lower in children as compared to adults. Children ≤6 years have 35% lower AUC than older children (14.4 (9.9-18.8) vs 22.0 (13.8-30.1) μg.h/mL) and children with HIV (CWHIV) had 35% lower rifampicin AUC than HIV negative children (17.3 (11.4-23.2) vs 26.5 (21.3-31.7) μg.h/mL). Heterogeneity and small sample sizes were major limitations. Conclusion There is large variability in outcomes with an average 82% favourable outcomes. Drug exposures are lower in children than in adults. Younger children and CWHIV are underexposed to rifampicin. Standardization of pharmacokinetic paediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing. View on Web

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Are psychedelics the answer to chronic pain: a review of current literature

alexandrossfakianakis shared this article with you from Inoreader Are psychedelics the answer to chronic pain: a review of current literature via Pain Practice Abstract Chronic pain is a common and complex problem, with an unknown etiology. Psychedelics like lysergic acid diethylamide (LSD) and psilocybin, may play a role in the management of chronic pain. Through activation of the serotonin-2A (5-HT2A) receptor, several neurophysiological responses result in the disruption of functional connections in brain regions associated with chronic pain. Healthy reconnections can be made through neuroplastic effects, resulting in sustained pain relief. However, this process is not fully understood and evidence of efficacy is limited and of low quality. In cancer and palliative related pain, the analgesic potential of psychedelics was established decades ago, and the current literature shows promising results on efficacy and safety in patients with cancer-related psychological distress. In other areas, patients suffering from severe headache disorders like migraine and cluster headache who have self-medicated with psychedelics report both acute and prophylactic efficacy of LSD and psilocybin. Randomized control trials are now being conducted to study the effects in cluster headache Furthermore, psychedelics have a generally favorable safety profile especially when compared to other analgesics like opioids. In addition, psychedelics do not have the addictive potential of opioids. Given the current epidemic use of opioids, and that patients are in desperate need of an alternative treatment, it is important that further research is conducted on the efficacy of psychedelics in chronic pain conditions. View on Web

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