Aim
This systematic review and network meta‐analysis aimed to evaluate the efficacy of adjunctive locally delivered antimicrobials, compared to subgingival instrumentation alone or plus a placebo, on ...changes in probing pocket depth (PPD) and clinical attachment level (CAL), in patients with residual pockets during supportive periodontal care.
Materials and methods
Literature search was performed with electronic databases and by hand until 31 May 2020. Primary outcome was the changes in PPD. The treatment effects between groups were estimated with weighted mean differences (WMD) with 95% confidence intervals (CI) and prediction intervals (PI) by using random‐effects network meta‐analysis.
Results
Twenty‐two studies were included. Significantly greater PPD reduction was achieved in chlorhexidine chip group (WMD: 0.65 mm, 95% CI: 0.21–1.10) and tetracycline fibre group (WMD: 0.64 mm, 95% CI: 0.20–1.08) over 6‐month follow‐up. Other adjunctive antimicrobial agents achieved non‐significant improvements compared to scaling and root planing alone. All differences between adjunctive therapies were statistically non‐significant. Similar findings were observed for CAL gain.
Conclusion
Adjunctive local antimicrobial agents achieved small additional PPD reduction and CAL gain in residual pockets for a follow‐up of up to 6 months. Tetracycline fibre and chlorhexidine chip achieved better results than other antimicrobials.
Background
Aldo‐keto reductase family 1 member B10 (AKR1B10) expression in oral squamous cell carcinoma (OSCC) tissue specimens is correlated with the progression and prognosis of OSCC.
Methods
...Saliva samples were obtained from 35 normal controls and 86 patients with OSCC before cancer surgery. The AKR1B10 levels were determined using enzyme‐linked immunosorbent assay (ELISA).
Results
The mean salivary AKR1B10 levels were significantly higher in the patients with OSCC than in the normal controls (P < .001). Higher salivary AKR1B10 levels were significantly associated with larger tumor size, more advanced clinical stage, and areca quid chewing habit. Patients with OSCC with a higher salivary AKR1B10 level (>646 pg/mL) had a significantly poorer survival than those with a lower (≤646 pg/mL) salivary AKR1B10 level (P = .026).
Conclusion
The salivary AKR1B10 level may be a promising biomarker for screening high‐risk patients with OSCC and monitoring the progression of OSCC.
Abstract
Context
As the number of medical school graduates continues to outpace the available residency training positions, applying for residency in the United States has become a highly competitive ...process, often associated with a low rate of selection and invitation for interview. The National Resident Matching Program (NRMP) Program Director survey provides data assessing factors considered by Program Directors (PD) in selecting and inviting candidates for interview. Assessing the evolution of these factors over time is efficacious to inform and guide prospective applicants toward improving preparation for residency application.
Objectives
We aim to synthesize NRMP data showing factors that PDs reported and rated as important in their decision to select and invite applicants for interview.
Methods
Data from residency PD surveys from 2008 to 2021 were accessed, but after applying inclusion/exclusion criteria, only the data from 2016 to 2020 were reviewed and analyzed. The NRMP survey reports provided two metrics that characterized PDs’ evaluation of the residency factors for interview, namely, “percent citing factor” and “average rating” on a 0 to 5 Likert-type scale. These two metrics were combined into an aggregate measure of importance (AI), and another measure of relative importance (RI) was constructed from normalizing the AI of each individual factor to the sum of the AI within each survey year.
Results
The top ranked factors were United States Medical Licensing Examination (USMLE) Step 1/Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Level 1, Letter of Recommendation (LOR) in the specialty, Medical Student Performance Evaluation (MSPE/Dean’s Letter), and USMLE Step 2 Clinical Knowledge (CK)/COMLEX Level 2 Cognitive Exam (CE) score, any failed attempt in USMLE/COMLEX, and perceived commitment to specialty. Factors rising in importance were Audition Elective/Rotation Within Your Department, Personal Statement (PS), Perceived Commitment to Specialty, Perceived Interest in Program, LOR in the Specialty, Other Life Experience, and Personal Prior Knowledge of the Applicant. Factors with declining importance were Interest in Academic Career, Awards or Special Honors in Basic Sciences, Graduate of Highly Regarded US Medical School, Awards or Special Honors in Clinical Clerkships, Lack of Gaps in Medical Education, Awards or Special Honors in Clerkship in Desired Specialty, and Consistency of Grades. Compared to the 2021 PD survey, our findings show continued predictive consistency, particularly related to specialty and program commitment.
Conclusions
The factors identified for the selection of medical school graduates for interview into a residency program reveal that PDs move toward a more integrated approach. Specifically, PDs are placing increasing emphasis on factors that border on subjective qualities more so than the more traditional, quantitative, and objective metrics. Medical students and educators need to continually apprise themselves of the NRMP data to inform students’ preparation endeavors throughout medical school to strengthen their application portfolios and enhance their competitiveness for the matching process.
B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism ...of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter. In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.
Background
Nucleophosmin/nucleoplasmin family 1 (NPM1) has broad physiological functions, such as DNA replication, transcription, ribosome biogenesis, and centrosome replication. This study explored ...the clinicopathological importance of NPM1 as a prognostic marker for oral squamous cell carcinoma (OSCC).
Methods
We collected specimens from 96 OSCC, 45 oral epithelial dysplasia (OED), and 29 normal oral mucosa (NOM). NPM1 expression was analyzed via immunohistochemistry. Correlations between NPM1and clinical parameters were analyzed using Student t test, chi‐squared test, and Kaplan‐Meier product‐limit method.
Results
The NPM1 labeling indices (LIs) were significantly higher in OSCCs than in NOM and oral OED. Higher NPM1 expression was significantly correlated with larger tumor size, nodal metastasis, and advanced clinical stage. Multivariate analysis revealed that higher NPM1 LIs were an unfavorable independent factor for survival.
Conclusions
Upregulated NPM1 is an independent biomarker of poor prognosis and NPM1 inhibitors may be promising in molecular targeted therapy against OSCC.
Background: Progression of diabetes‐associated periodontal destruction and the roles of advanced glycation end products (AGEs) are investigated.
Methods: Diabetes was induced by streptozocotin ...injection, and periodontitis was induced via silk ligature placement with Porphyromonas gingivalis lipopolysaccharide injection in 64 Sprague‐Dawley rats for 7 to 21 days. The quality of alveolar bone and attachment loss (AL) were measured by microcomputed tomography and histology. Destruction profiles were evaluated by histology, histochemistry, immunohistochemistry, and quantitative assessments of inflammatory cells, expression of receptors for AGEs (RAGE), tartrate‐resistant acid phosphatase, and proliferating cell nuclear antigen.
Results: Without periodontitis induction, there was no obvious morphologic change in the periodontium, although slight elevations of AGEs and RAGE levels were noted in animals with diabetes. In the group with experimental periodontitis, significant periodontal bone loss was noted in animals both with and without diabetes from day 7, with more progressive bone loss in animals with diabetes during days 14 to 21. Histologically, the disruption of attachment and inflammation were observed from day 7, but subsequently subsided in animals without diabetes. A stronger and more prolonged response with significant AL was observed in animals with diabetes. Stronger inflammation, attenuated and persistent resorptive activity, and weaker proliferating potential were demonstrated by animals with diabetes. AGE deposition and RAGE expression were noted in animals without diabetes but with periodontitis, although levels were considerably elevated in the later stages in animals with diabetes.
Conclusions: Diabetes augments periodontal destruction by reducing the proliferating capability and activating resorptive activities. Presence of the AGE‐RAGE axis without diabetes implies that it is involved in the regulation of inflammation.
The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to ...nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c(+) dendritic and CD11b(+) infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.
Objective and Background
Gingival overgrowth (GO) is a common side effect of some drugs such as anticonvulsants, immunosuppressant, and calcium channel blockers. Among them, the antiepileptic agent ...phenytoin is the most common agent related to this condition due to its high incidence. Transforming growth factor β (TGFβ) importantly contributes to the pathogenesis of GO. Connective tissue growth factor (CTGF or CCN2) is a key mediator of tissue fibrosis and is positively associated with the degree of fibrosis in GO. We previously showed that Src, c‐jun N‐terminal kinase, and Smad3 mediate TGFβ1‐induced CCN2 protein expression in human gingival fibroblasts (HGFs). This study investigates whether phenytoin can induce CCN2 synthesis through activated latent TGFβ in HGFs and its mechanisms.
Methods
CCN2 synthesis, latent TGFβ1 activation, and cellular reactive oxygen species (ROS) generation in HGFs were studied using western blot analysis, a TGFβ1 Emax® ImmunoAssay System, and 2′,7′‐dichlorodihydrofluorescein diacetate (an oxidation‐sensitive fluorescent probe), respectively.
Results
Phenytoin significantly stimulated CCN2 synthesis, latent TGFβ1 activation, and ROS generation in HGFs. Addition of an TGFβ‐neutralizing antibody, TGFβ receptor kinase inhibitor SB431542, and Smad3 inhibitor SIS3 completely inhibited phenytoin‐induced CCN2 synthesis. General antioxidant N‐acetylcysteine, NADPH oxidase (NOX) inhibitor diphenylene iodonium, and specific NOX4 inhibitor plumbagin almost completely suppressed phenytoin‐induced total cellular ROS and latent TGFβ1 activation. Curcumin dose‐dependently decreased phenytoin‐induced TGFβ1 activation and CCN2 synthesis in HGFs.
Conclusions
Our findings indicated that NOX4‐derived ROS play pivotal roles in phenytoin‐induced latent TGFβ1 activation. Molecular targeting the phenytoin/NOX4/ROS/TGFβ1 pathway may provide promising strategies for the prevention and treatment of GO. Curcumin‐inhibited phenytoin‐induced CCN2 synthesis is caused by the suppression of latent TGFβ1 activation.
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