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Κυριακή 4 Δεκεμβρίου 2022

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

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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.

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

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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.
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Necrotic facial ulceration caused by cowpox virus

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Abstract

A 56-year-old Caucasian lady presented to the maxillofacial department with a lesion on her left cheek with associated lethargy and fevers

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Assessment of exercise‐induced hypoalgesia in chronic low back pain and potential associations with psychological factors and central sensitization symptoms: A case‐control study

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Abstract

Introduction

Exercise is the most recommended treatment for chronic low back pain (CLBP) and is effective in reducing pain, but the mechanisms underlying its effects remain poorly understood. Exercise-induced hypoalgesia (EIH) may play a role and is thought to be driven by central pain modulation mechanisms. However, EIH appears to be disrupted in many chronic pain conditions and its presence in people with CLBP remains unclear. As people suffering from chronic pain often exhibit psychological factors and central sensitization symptoms influencing pain perception, EIH might be associated to these factors.

Objective

To compare the level of EIH between participants with and without CLBP following back and wrist exercises and to assess the associations between EIH, psychological factors and central sensitization inventory score (CSI) in CLBP.

Method

Twenty-eight participants with CLBP and 23 without pain were recruited. Pressure pain thresholds (PPT) were measured at 4 sites (2 bony sites = capitate, S1 | 2 muscle sites = wrist flexors, lumbar erector spinae) before and after each of two exercises (wrist flexion and lumbar extension). EIH was defined as percent change in PPT from pre-to-post-exercise. Participants with CLBP also completed questionnaires to measure psychological factors (e.g. kinesiophobia, catastrophizing, anxiety, self-efficacy) and symptoms of central sensitization (CSI), and correlations with EIH was calculated.

Results

After wrist exercise, EIH measured at the muscle sites was lower in the CLBP group compared to the pain-free group (p=0.047) but no differences were found at bony sites (p=0.49). No significant differences for EIH were observed following back exercise at muscle sites (p=0.14) or at bony sites (p=0.65). EIH was not correlated with any psychological factors or to the CSI score.

Conclusion

The lower EIH following wrist exercises may represent an alteration in pain modulation control in CLBP. However, psychological factors and central sensitization symptoms may not explain the differences observed.

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

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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.

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The impact of clinical trial enrollment on specialty palliative care utilization in pediatric patients with high‐grade gliomas

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Abstract

Background

Palliative care (PC) provides numerous benefits for children with cancer. Pediatric patients with high-grade glioma (HGG) are particularly well suited for early PC involvement given their high symptom burden and poor prognosis. However, studies continue to reveal that children with cancer, including HGG, have delayed PC involvement. We hypothesized that clinical trial enrollment may lead to a lack of or delay in PC involvement in this population.

Procedure

For each patient in our cohort of 43 pediatric patients with HGG, demographic, diagnostic, therapeutic, clinical trial enrollment, and PC information were collected. Statistical analysis was performed comparing PC characteristics between patients who did and did not enroll in a clinical trial.

Results

Seventy-two percent of patients had at least one visit with a PC provider. Fifty-six percent of patients enrolled in a clinical trial with HGG-directed therapy. Seventy-one percent of patients who enrolled in a clinical trial received specialty PC compared to 74% of non-trial participants (p = 1.000). Patients who enrolled in clinical trials received PC earlier in their disease course measured in days before death (mean = 177 days) compared to those who did not enroll (mean = 113 days, p = .180), though not statistically significant.

Conclusions

The prevalence of clinical trial enrollment is high in patients with HGG and will likely increase as the genomic/epigenomic landscape of these tumors is better understood. As such, our data reassuringly suggest that trial participation does not interfere with the receipt of specialty PC in this population.

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Comparison of quality of life and psychological distress in patients with tongue cancer undergoing a total/subtotal glossectomy or extended hemiglossectomy and free flap transfer: a prospective evaluation

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The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after su...
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The Management of Salivary Fistulas

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Semin Plast Surg
DOI: 10.1055/s-0042-1759561

Postoperative salivary fistula is an especially undesirable complication because it can be difficult to address, may delay postoperative radiation, and always delays enteral nutrition. Patients who are malnourished, have already undergone radiotherapy, or are hypothyroid are at higher risk of developing this problem. Conservative measures work in most patients, but a significant percentage of patients require intervention beyond pr essure dressings and tincture of time. Medications, hyperbaric oxygen therapy, and surgical intervention may be required when fistulas do not heal in a timely manner. Decisions about the approach and timing of more aggressive interventions are part of the art of medicine since definitive scientific protocols are lacking.
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