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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Plasma Aβ42/Aβ40 ratios are not reduced in older people living with HIV

alexandrossfakianakis shared this article with you from Inoreader Plasma Aβ42/Aβ40 ratios are not reduced in older people living with HIV via Clinical Infectious Diseases Advance Access Abstract Background As people with HIV (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders, e.g., Alzheimer disease (AD), and if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically-available blood biomarker test for AD (plasma Aβ42/Aβ40 ratio), in cognitively-normal (CN) or cognitively-impaired (CI) PWH and people without HIV (PWoH) who were CN or with symptomatic AD. Methods 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, magnetic resonance imaging (MRI), and completed a neuropsychological battery or Clinical Dementia Rating scale (CDR). Participants were categorized by impairment (PWH_CN n = 43; PWH_CI n = 23; PWoH_CN n = 138; PWoH_AD n = 57). Plasma Aβ42 and Aβ40 concentrations were obtained using a liquid chromatography-tandem mass spectrometry method to calculate the PrecivityAD® Amyloid Probability Score (APS). The APS incorporates age and apolipoprotein E proteotype into a risk score for brain amyloidosis. Plasma Aβ42/Aβ40 and APS were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only). Results The plasma Aβ42/Aβ40 ratio was significantly lower, and APS higher, in PWoH_AD compared to other groups. A lower Aβ42/Aβ40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The Aβ42/Aβ40 ratio and APS were not associated with cognition or HIV clinical measures for PWH. Conclusions The plasma Aβ42/Aβ40 ratio can serve as a screening tool for AD and may help differentiate effects of HIV from AD within PWH, but larger studies with older PWH are needed. View on Web

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ACE2 PET to Reveal the Dynamic Patterns of ACE2 Recovery in an Infection Model with Pseudo Corona Virus

alexandrossfakianakis shared this article with you from Inoreader ACE2 PET to Reveal the Dynamic Patterns of ACE2 Recovery in an Infection Model with Pseudo Corona Virus via Journal of Medical Virology Abstract Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potentials to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virus-host interaction, 68Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation, and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period were visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time period-dependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in heart, liver, kidneys, lungs and so on, but liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days P.I., with brain and genitals still of a decreased SUVACE2, meanwhile, kidneys were of an increased SUVACE2. These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was of the superiority on earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUVACE2 and the ACE2 specificity were further confirmed. In conclusion, 68Ga-cyc-DX600 was developed as an ACE2-specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference an d approach to explore the ACE2-related pathological basis of sequelae in long COVID. 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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Drug‐induced radiation recall reactions and non‐anticancer drugs: A descriptive analysis from VigiBase®

alexandrossfakianakis shared this article with you from Inoreader Drug‐induced radiation recall reactions and non‐anticancer drugs: A descriptive analysis from VigiBase® via Fundamental & Clinical Pharmacology Abstract Background Radiation recall reactions are inflammatory reactions confined to previously irradiated tissues, often of drug-induced etiology, particularly with anticancer therapies. Other drugs, in particular COVID-19 vaccines, may also be involved. Objective To describe radiation recall reactions under non-anticancer drugs more precisely. Material and method We extracted the cases of radiation recall reactions associated with non-anticancer drugs from WHO pharmacovigilance database VigiBase®. We performed two analyses from this extraction: a global analysis and an analysis focusing on vaccination-related issues. Results We extracted 120 cases corresponding to 269 drugs, of which 130 were non-anticancer (22 vaccines). Among the non-anticancer drugs, tozinameran was the most reported treatment (4.46% of cases), followed by levofloxacin (2.97%) and folinic acid (2.60%), dexamethasone (2.23), ChAdOx1 nCoV-19 vaccine and prednisone (1.86% each). Among vaccines, tozinameran (54.55% of cases) was the most reported, followed by ChAdOx1 nCoV-19 (22.73%), HPV & inactivated influenza vaccine (9.09% each), and elasomeran (4.55%). Conclusion Our study first describes the occurrence of radiation recall reactions during non-anticancer treatment. It also highlights a potential safety signal with COVID-19 vaccines. View on Web

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Temporal trends in the incidence of malignant and non-malignant primary brain and central nervous system tumors by method of diagnosis in England, 1993-2017

alexandrossfakianakis shared this article with you from Inoreader Temporal trends in the incidence of malignant and non-malignant primary brain and central nervous system tumors by method of diagnosis in England, 1993-2017 via Neuro-Oncology Advance Access Abstract Background Several studies report increasing incidence of primary CNS tumors. The reasons for this are unclear. Methods Data on all 188,340 individuals diagnosed with a primary CNS tumor in England (1993-2017) were obtained from the National Cancer Registry. Data on all CT head and MRI brain scans in England (2013-2017) were obtained from NHS Digital. Age-sex-standardized annual incidence rates per 100,000 population (ASR) were calculated by calendar year, tumor behavior, tumor location and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC). Results The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: 1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: -0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically c onfirmed, the ASR increased modestly (AAPC: 1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those aged 65+. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013-2017, with especially large increases in 65-84 and 85+ year olds (AAPCs: 18.4% and 22.5%). Conclusion Increases in CNS tumor incidence in England are largely attributable to greater detection of benign tumors. This could be the result of increasing use of neuroimaging, particularly CT head scans in A&E in people aged 65+. 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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Rapid Detection of Monkeypox Virus by Multiple Cross Displacement Amplification Combined with Nanoparticle‐based Biosensor platform

alexandrossfakianakis shared this article with you from Inoreader Rapid Detection of Monkeypox Virus by Multiple Cross Displacement Amplification Combined with Nanoparticle‐based Biosensor platform via Journal of Medical Virology Abstract The current outbreak of monkeypox virus (MPXV) has become a public health emergency of international concern that highlights the need for rapid, sensitive MPXV diagnostic assays. Here, we combined isothermal multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow biosensor (LFB) to devise a diagnostic test for the diagnosis of MPXV infection (called MPXV-MCDA-LFB) and differentiation of West and Central African MPXV isolates. The MPXV-MCDA-LFB protocol conducts isothermal MCDA reaction for DNA templates followed by LFB detection of preamplification target sequences. Two MCDA primer sets were designed targeting the D41L and ATI genes of Central and West African MPXV isolates, respectively, and the optimal condition of two MCDA reactions was 64 ºC for 30 min. The two MCDA reactions were decoded by LFB, which was devised for detecting three targets, including two amplicons yielded from two MCDA reactions and a chromatography contr ol. Thus, the MPXV-MCDA-LFB assay could be completed within 50 min including rapid template preparation (15 min), MCDA reaction (30 min) and reporting of result (< 5 min). The MPXV-MCDA-LFB method is very sensitive and can detect the target genes (D14L and ATI) with as low as five copies of plasmid template per reaction and 12.5 copies of pseudovirus in human blood samples. MPXV-MCDA-LFB assay does not cross-react with non-MPXV templates, validating its specificity. Therefore, the MPXV-MCDA-LFB assay developed here is a useful tool for rapid and reliable diagnosis of MPXV infection. 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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