25‐Hydroxycholesterol induces odontoclastic differentiation through RANK–RANKL upregulation and NF‐κB activation in odontoblast‐like MDPC‐23 cells: An in vitro study

alexandrossfakianakis shared this article with you from Inoreader 25‐Hydroxycholesterol induces odontoclastic differentiation through RANK–RANKL upregulation and NF‐κB activation in odontoblast‐like MDPC‐23 cells: An in vitro study via International Endodontic Journal Abstract Aim The physiological effects and cellular mechanism of 25-hydroxycholesterol (25-HC), which is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase (CH25H) expressed under inflammatory conditions, are still largely unknown during odontoclastogenesis. This study aimed to evaluate a 25-HC-induced odontoclastogenesis and its cellular mechanisms in odontoblast-like MDPC-23 cells. Methodology To investigate 25-HC-induced odontoclastogenesis of MDPC-23 cells and its cellular mechanism, haemotoxylin and eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, dentine resorption assay, zymography, reactive oxygen species (ROS) detection, immunocytochemistry, and nuclear translocation were performed. The experimental values are presented as mean ± standard deviation and were compared using analysis of variance, followed by post-hoc multiple comparison (Tukey's test) using SPSS software version 22 (IBM Corp.). A P value <0.05 was considered statistically significant. Results Lipopolysaccharide or receptor activator of nuclear factor-κB ligand (RANKL) induced the synthesis of 25-HC via the expression of CH25H in MDPC-23 cells (p<0.01). Multinucleated giant cells with morphological characteristics and TRAP activity of the odontoclast were increased by 25-HC in MDPC-23 cells (p<0.01). Moreover, 25-HC increased dentine resorption through the expression and activity of matrix metalloproteinases in MDPC-23 cells. It not only increased the expression of odontoclastogenic biomarkers but also translocated cytosolic nuclear factor-κB (NF-κB) to the nucleus in MDPC-23 cells. Additionally, 25-HC not only increased the production of ROS (p<0.01), expression of inflammatory mediators (p<0.01), pro-inflammatory cytokines, receptor activator of NF-κB (RANK), and RANKL but also suppressed the expression of osteoprotegerin (OPG) in MDPC-23 cells. In contrast, CDDO-Me, a chemical NF-κB inhibitor, decreased TRAP activity (p<0.01) and downregulated the expression of the odontoclastogenic biomarkers, including RANK and RANKL, in MDPC-23 cells. Conclusion 25-HC induced odontoclastogenesis by modulating the RANK–RANKL–OPG axis via NF-κB activation in MDPC-23 cells. Therefore, these findings provide that 25-HC derived from cholesterol metabolism may be involved in the pathophysiological etiological factors of internal tooth resorption. View on Web

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Progress of triazole antifungal agent posaconazole in individualized therapy

alexandrossfakianakis shared this article with you from Inoreader Progress of triazole antifungal agent posaconazole in individualized therapy via Journal of Clinical Pharmacy and Therapeutics Posaconazole is a second-generation triazole antifungal agent with a broad antibacterial spectrum, strong antifungal activity, high safety tolerability and cost effectiveness compared to other azole antifungal agents. The literature on posaconazole shows an increasing trend year on year. However, the pharmacokinetic process of the drug is highly individual and its blood concentration is influenced by various factors such as the drug, the patient and the food, resulting in a failure to achieve preventive or therapeutic effects. In this paper, we present a review of the individualized therapy of posaconazole from therapeutic drug monitoring, population pharmacokinetics and Monte Carlo simulation. This review will provide a reference for the rational use of posaconazole and provide theoretical support for further individualized treatment studies. Abstract What is known and objective Posaconazole is the second-generation triazole antifungal agent with widespread clinical application. Posaconazole exposure is influenced by various factors such as drug interactions, disease state and diet, resulting in a high interindividual variability in many patients and failure to ensure therapeutic efficacy. Therefore, it is necessary to conduct individualized therapy on posaconazole to ensure the efficacy and safety of treatment. Methods Articles were identified through PubMed using the keywords such as "posaconazole," "therapeutic drug monitoring" and "Population pharmacokinetics" from 1 January 2001 to 30 April 2022. Results and discussion In this paper, we review the individualized treatment studies of posaconazole from the three aspects of therapeutic drug monitoring, population pharmacokinetic study and Monte Carlo simulation to provide reference for in-depth individualized posaconazole dosing studies. What is new and conclusion This review suggests that therapeutic drug monitoring should be performed in patients taking posaconazole to adjust the dosage and assess the efficacy and cost-effectiveness of posaconazole under different clinical conditions and different dosing regimens through Monte Carlo simulations. In the future, a more detailed delineation and comprehensive examination of posaconazole PPK for specific populations requires further study. View on Web

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In-utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study

alexandrossfakianakis shared this article with you from Inoreader In-utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study via Epidemiology - Published Ahead-of-Print Background: Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy in offspring is limited. We aimed to examine the effects of pre-gestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. Methods: In a population-based study, we included all live births in Ontario, Canada, between 2002–2017 followed up through 2018 (n=2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). Results: During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk {hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]} after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 (0.77, 1.06)). Our mediation analysis estimated that LGA explained 14% of the PDGM–CP association. Conclusions: In this population-based birth cohort study, maternal pre-gestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Constructing a Mixed Simulation With 360° Virtual Reality and a High-Fidelity Simulator: Usability and Feasibility Assessment

alexandrossfakianakis shared this article with you from Inoreader Constructing a Mixed Simulation With 360° Virtual Reality and a High-Fidelity Simulator: Usability and Feasibility Assessment via Computers Informatics Nursing - Published Ahead-of-Print Virtual reality technology has been adopted to overcome barriers of conventional simulation. This study was conducted to determine the impact of mixed simulation (a 360° virtual reality and a high-fidelity simulator) on learning how to provide nursing care for patients with arrhythmia. A total of 49 students were randomly assigned to intervention (n = 25) and control (n = 23) groups. They were given four arrhythmia cases with a 360° virtual reality system first followed by a manikin-based simulation. The mixed simulation group showed greater improvement in knowledge, higher decision-making competency in "knowing and acting" (P = .025) and "seeking information from instructors" (P = .049), and lower anxiety in "using resources to gather information" (P = .031). Study participants achieved a good level of empathy (3.28 ± 0.72) and liked the program (4.56 ± 0.60). They were satisfied with the program (4.48 ± 0.65). These findings provide new insight into learning through blending of new technology. When the 360° virtual reality was used with existing manikin-based simulation, they effectively reinforced one another. The 360° virtual reality can be an effective strategy to ensure active participation to gain a comprehensive understanding of and empathy for patients. View on Web

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The Effect of Two Different Simulation Modalities in Palliative Care Teaching on Nursing Students' Knowledge, Satisfaction, Self-confidence, and Skills: A Randomized Controlled Trial

alexandrossfakianakis shared this article with you from Inoreader The Effect of Two Different Simulation Modalities in Palliative Care Teaching on Nursing Students' Knowledge, Satisfaction, Self-confidence, and Skills: A Randomized Controlled Trial via Computers Informatics Nursing - Published Ahead-of-Print Nursing students from developing countries have limited opportunities to experience palliative care. Standardized patient and low-fidelity simulations can provide realistic palliative care experiences for students. However, limited research is available on simulation-based education in Palestine. Testing and using these two types of simulation methods may be the best solution for developing countries that lack adequate resources. This study aimed to test the effects of low-fidelity simulation compared with standardized patient simulation in palliative care teaching on nursing students' knowledge, satisfaction, confidenc e, and skills. The study was a randomized controlled trial of 70 nursing students in their sophomore year. Students' knowledge was assessed with the Palliative Care Quiz for Nursing test; satisfaction and confidence with the Learner Satisfaction and Self-confidence in Learning; and skills rated by two researchers. Students' knowledge improved significantly on the posttest compared with the pretest, without significant differences between both groups. The findings showed that the utilization of the two methods in students' clinical training for scenario has the same effect on the satisfaction and confidence. The skills of the standardized patient group improved significantly more than the low-fidelity group. The study revealed that both simulation modalities are effective for palliative care nursing students. View on Web

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Higher SARS‐CoV‐2 shedding in exhaled aerosol probably contributed to the enhanced transmissibility of Omicron BA.5 subvariant

alexandrossfakianakis shared this article with you from Inoreader Higher SARS‐CoV‐2 shedding in exhaled aerosol probably contributed to the enhanced transmissibility of Omicron BA.5 subvariant via Journal of Medical Virology Abstract The global pandemic of the BA.5 subvariant had moved from prediction to reality. In this study, we compared SARS-CoV-2 aerosol emissions from patients with BA.2 or BA.5 subvariant infection. First, patients with BA.2 subvariant infection had higher upper respiratory viral loads than patients with BA.5 subvariant infection. However, the average breath emission rate (BER) of patients with BA.5 subvariant infection, which represented the concentration of exhaled SARS-CoV-2 aerosols, was nearly 40 times higher than that of patients with BA.2 subvariant. Second, aerosols exhaled by patients with BA.5 subvariant infection exhibited SARS-CoV-2 RNA detection positive rate than patients with BA.1 or BA.2 subvariant infection. Meanwhile, for BA.5 subvariant infection, patients that exhaled infectious SARS-CoV-2 aerosols accounted for 14.8% of all patients. Third, since the onset of COVID-19, the SARS-CoV-2 RNA detection signals of throat swabs showed a gradual decline trend, although the de cline process was accompanied by fluctuations. Overall, the monitoring of infectious SARS-CoV-2 aerosols may provide the data support for the transmissibility evaluation of the Omicron BA.5 subvariant. This article is protected by copyright. All rights reserved. View on Web

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High incidence of virus among respiratory pathogens in children with lower respiratory tract infection

alexandrossfakianakis shared this article with you from Inoreader High incidence of virus among respiratory pathogens in children with lower respiratory tract infection in northwestern China via Journal of Medical Virology Abstract Background Lower respiratory tract infection (LRTI) is one of the major reasons for the childhood mortality that threaten the health of the public. We aimed to investigate the epidemiological pathogens and their infection analysis among children with LRTI. Methods Sputum specimens were collected for PCR detection and microbiological tests to identify the viral infection and bacterial infection. The serological specimens were separated from venous blood using for Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) detection. Results Virus was confirmed in 86.2% of the children. Human Rhinovirus (HRV, 38.3%), Respiratory Syncytial virus (RSV, 32.1%) and Parainfluenza Virus type 3 (PIV3, 27.2%) were the most frequently identified pathogens. Patients with viral and bacterial co-infection showed younger age (P=0.032), higher propotion of wheezing rales (P=0.032), three depressions sign (P=0.028) and tachypnea (P=0.038), and more likely associated with sever pneumonia (P=0.035). Additionally, older children were more susceptible with viral-atypical bacterial co-infection (P=0.032). Vomiting (P=0.011) and fever (P=0.003) were more likely to occur in children with viral-atypical bacterial co-infection. Conclusions Attention should be paid on the virus infection of LRTI, viral-bacterial co-infection and viral-atypical bacterial co-infection may have detrimental impact on the gravity of LTRI. This article is protected by copyright. All rights reserved. View on Web

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Comparison of Secondary Attack Rate and Viable Virus Shedding between Patients with SARS‐CoV‐2 Delta and Omicron Variants: A Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Comparison of Secondary Attack Rate and Viable Virus Shedding between Patients with SARS‐CoV‐2 Delta and Omicron Variants: A Prospective Cohort Study via Journal of Medical Virology Abstract Backgrounds There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. Methods We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. Results A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further five patients gave undetectable or inconclusive RNA PCR results and one was suspected of being co-infected with both variants. Omicron group had a higher secondary attack rate (31% [38/124]) versus 7% [34/456], p<0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4 days, IQR [1 -7], vs. 8.5 days, IQR [5 – 12 days], p<0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR 1.96), and immunocompromised status (HR 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or 1st booster-vaccinated status (HR 0.49), and Omicron infection (HR 0.44) were independently associated with shorter viable virus s hedding. Conclusion Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections. This article is protected by copyright. All rights reserved. View on Web

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Necrotic facial ulceration caused by cowpox virus

alexandrossfakianakis shared this article with you from Inoreader Necrotic facial ulceration caused by cowpox virus via Journal of Medical Virology Abstract A 56-year-old Caucasian lady presented to the maxillofacial department with a lesion on her left cheek with associated lethargy and fevers This article is protected by copyright. All rights reserved. View on Web

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Tideglusib enhances odontogenic differentiation in human dental pulp stem cells in vitro

alexandrossfakianakis shared this article with you from Inoreader Tideglusib enhances odontogenic differentiation in human dental pulp stem cells in vitro via International Endodontic Journal Abstract Aim Tideglusib is a small molecule agonist of the canonical Wnt pathway. The present study investigated the influence of Tideglusib on human dental pulp stem cell (hDPSC) proliferation, apoptosis, migration, and odonto/osteogenic differentiation. Methodology hDPSCs were treated with 50 nM, 100 nM, or 200 nM Tideglusib. β-catenin accumulation was detected by immunofluorescence staining. Colony forming unit ability was assessed by staining with Coomassie blue. Cell cycle progression and cell apoptosis were investigated using flow cytometry. Cell migration was examined using an in vitro wound healing assay. Osteogenic differentiation was examined using alkaline phosphatase (ALP) staining, alizarin red s staining, and osteogenic-related gene expression. The gene expression profile was examined using a high throughput RNA sequencing technique. All experiments were repeated using cells derived from at least four different donors (n = 4). The Mann Whitney U test was used to identify significant differences for two independent group comparisons. For three or more group comparison, statistical differences were assessed using the Kruskal Wallis test followed by a pairwise comparison. The significance level was set at 5% (p< /i> < 0.05). Results Tideglusib activated the Wnt signaling pathway in hDPSCs as demonstrated by an increase in cytoplasmic β-catenin accumulation and nuclear translocation. Tideglusib did not affect hDPSC proliferation, cell cycle progression, cell apoptosis, or cell migration. In contrast, 50 nM and 100 nM Tideglusib significantly enhanced mineralisation and osteogenic marker gene expression (RUNX2, ALP, BMP2, and DSPP) (p < 0.05). Conclusions Tideglusib enhanced the odonto/osteogenic differentiation of hDPSCs. Therefore, incorporating this bioactive molecule in a pulp capping material could be a promising strategy to promote dentine repair. View on Web

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