Association between circulating 25‐hydroxyvitamin D metabolites and periodontitis: Results from the NHANES 2009‐2012 and Mendelian randomization study

alexandrossfakianakis shared this article with you from Inoreader Association between circulating 25‐hydroxyvitamin D metabolites and periodontitis: Results from the NHANES 2009‐2012 and Mendelian randomization study via Journal of Clinical Periodontology Abstract Aim This study sought to investigate associations of 25(OH)D metabolites with periodontitis, and to assess causality using Mendelian randomization (MR). Methods This study included 7,246 participants of the National Health and Nutrition Examination Survey, 2009–2012. The association of periodontitis with 25(OH)D metabolites was assessed using multivariable logistic regression analysis. 2-sample MR for 25(OH)D, 25(OH)D3, and C3-epi-25(OH)D3 with periodontitis (n = 17,353 cases/28,210 controls) was conducted. The principal analysis was inverse-variance-weighted approach. We controlled for horizontal pleiotropy using five additional methods. Results Based on the observational study, each 1-point increase in standard deviation of 25(OH)D lowered the risk of periodontitis by 15% (OR = 0.85, 95% CI: 0.78–0.93, P = 0.006) after multivariable adjustment. A similar relationship was observed between 25(OH)D3 and periodontitis (OR = 0.88, 95% CI: 0.80–0.97, P = 0.031). Furthermore, a potential nonlinear association was found between periodontitis with both 25(OH)D and 25(OH)D3. However, C3-epi-25(OH)D3 was not found to be associated with periodontitis risk. IVW-MR showed that periodontitis risk was not significantly associated with genetically increased levels of 25(OH)D (OR = 1.02, 95% CI: 0.90–1.16, P = 0.732), 25(OH)D3 (OR = 1.04, 95% CI: 0.93–1.17, P = 0.472), and C3-epi-25(OH)D3 (OR = 1.11, 95% CI: 0.87–1.41, P = 0.400). The pleiotropy-robust MR approaches yielded similar results after we had eliminated the variants with horizontal pleiotropy risk. Conclusion Cross-sectional observational analysis identified significant relationships between periodontitis with 25(OH)D metabolites, while findings based on MR study do not support a causal role. This article is protected by copyright. All rights reserved. View on Web

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Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin

alexandrossfakianakis shared this article with you from Inoreader Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin via Neuro-Oncology Advance Access Abstract Background Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. Methods SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. Results High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. Conclusio ns High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin. View on Web

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Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development

alexandrossfakianakis shared this article with you from Inoreader Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development via Helicobacter Abstract Background and Aim Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer (GC), with the number of eradication therapy cases on the rise. However, GC can still occur after successful treatment, and the histological differences prior to eradication in patients with and without GC are unclear. This study investigated the pre-treatment histological risk factors for GC development following eradication therapy. Methods We retrospectively enrolled consecutive adult patients diagnosed as having H. pylori infection between April 2004 and December 2018. Atrophy and intestinal metaplasia (IM) were histologically assessed according to the updated Sydney System. The operative link on gastritis assessment and the operative link on gastric intestinal metaplasia (OLGIM) were evaluated as well. Results Of the 247 patients analyzed in this study, 11 (4.5%) experienced GC after eradication therapy. Histological IM scores in the GC group were significantly higher at all gastric biopsy sites (p < .05), and the proportion of OLGIM III/IV stage was significantly greater in GC patients (81.8% vs. 31.8%, p < .01). For GC prediction, the area under the receiver operating characteristic curve for IM score at the lesser curvature of the corpus was the highest among all biopsy sites and not inferior to OLGIM results. Conclusions Patients with histological IM prior to H. pylori eradication, especially at the lesser curvature of the corpus, may be at elevated risk for GC development after eradication therapy and require close surveillance. View on Web

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Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

alexandrossfakianakis shared this article with you from Inoreader Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma via Journal of Clinical Pharmacy and Therapeutics In this study, including 54 PCNSL patients with 175 HD-MTX-based chemotherapy courses, the rate of AKI and myelosuppression increased significantly in patients treated with HD-MTX co-administered with VDS. We also found a significant correlation between MTX pharmacokinetics, eGFR before MTX infusion, and toxicity. Abstract What is Known and Objective Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice. Methods Fifty-four patients who received 175 courses of MTX at 3–8 g/m2 between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression. Results and Discussion A total of 124 adverse events occurred after MTX infusion. Using independent sample t-tests, we found that patients with myelosuppression had higher MTX area under the concentration-time curve up to 48 h after infusion (AUC0-48h) (p = 0.001) and MTX peak concentration (Cmax) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi-square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044–1.116, p = 6.9 × 10−6; OR = 0.808, 95% CI 0.711–0.917, p = 0.001, respectiv ely). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935–0.986, p = 0.003; OR = 1.009, 95% CI 1.001–1.017, p = 0.034; OR = 5.463, 95% CI 1.793–16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972–0.998, p = 0.025; OR = 3.070, 95% CI 1.032–9.133, p = 0.044). What is New and Conclusion Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities. View on Web

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The development of the Standardized Tool for the Assessment of Bruxism (STAB): An international road map

alexandrossfakianakis shared this article with you from Inoreader The development of the Standardized Tool for the Assessment of Bruxism (STAB): An international road map via Journal of Oral Rehabilitation Abstract This paper summarizes the background reasoning and work that led to the selection of the items included in the Standardized Tool for the Assessment of Bruxism (STAB), also introducing the list of items. The instrument is currently being tested for face validity and on-field comprehension. The underlying premise is that the different motor activities included in the bruxism spectrum (e.g., clenching versus grinding, with or without teeth contact) potentially need to be discriminated from each other, based on their purportedly different etiology, comorbidities, and potential consequences. Focus should be on a valid impression of the activities' frequency, intensity, and duration. The methods that can be used for the above purposes can be grouped into strategies that collect information from the patient's history (subject-based), from the clinical assessment performed by an examiner (clinically based), or from the use of instruments to measure certain outcomes (instrumentally based). The three strategies can apply to all aspects of bruxism (i.e., status, comorbid conditions, etiology, and consequences). The STAB will help gathering information on many aspects, factors, and conditions that are currently poorly investigated in the field of bruxism. To this purpose, it is divided into two axes. Axis A includes the self-reported information on bruxism status and potential consequences (subject-based report) together with the clinical (examiner report) and instrumental assessment (technology report). Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid role for bruxism. This comprehensive multidimensional assessment system will allow building predictive model for clinical and research purposes. View on Web

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Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function

alexandrossfakianakis shared this article with you from Inoreader Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractThe synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48  h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that th... View on Web

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Disrupted tenogenesis in masseter as a potential cause of micrognathia

alexandrossfakianakis shared this article with you from Inoreader Disrupted tenogenesis in masseter as a potential cause of micrognathia via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 18 October 2022; doi:10.1038/s41368-022-00196-y Disrupted tenogenesis in masseter as a potential cause of micrognathia View on Web

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