Anti-infective Efficacy of Mechanical Debridement with Adjunctive Modalities on Clinical and Cytokine Parameters in Treatment of Chronic Periodontitis: Randomized Controlled Clinical Trial.

OBJECTIVES: Periodontal debridement involves conventional scaling and root planing (SRP) along with variant forms of adjunctive therapies. In the present clinical trial, we investigated if the adjunctive use of HybenX gel or diode laser along with SRP could provide a favorable outcome for the treatment of chronic periodontitis. MATERIALS AND METHODS: The present study involved 60 subjects diagnosed with chronic periodontitis who were randomly assigned as test groups (laser or HybenX) or control group (SRP alone). The primary outcomes of the clinical trial were pocket probing depth (PPD) and clinical attachment level (CAL), which was evaluated at baseline and at third-month time interval. Additionally, secondary outcomes included estimation of reduction in inflammatory mediators interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in gingival crevicular fluid using enzyme-linked immunosorbent assay at baseline and third-month intervals. STATISTICAL ANALYSIS: Normality determination was checked using Shapiro-Wilk test. Since the data was not normally distributed, nonparametric tests were applied. The comparison of clinical parameters between the groups was analyzed with Kruskal-Wallis test. Wilcoxon sign rank test was used to compare the pairwise comparison of clinical parameters among the groups from baseline to third-month follow-up. The inflammatory mediators at various time points were compared using a One-way analysis of variance test, and the inflammatory mediators in each study group were compared using a paired t-test. RESULTS: Both the test groups demonstrated a decrease in PPD and CAL. However, the HybenX group exhibited statistically significant reduction at the end of the third-month study interval compared to the laser group and SRP alone. Further, the secondary outcome IL-1ß and TNF-α analysis exhibited statistically significant reduction in all the groups posttherapy. CONCLUSION: The adjunctive application of HybenX gel yielded an advantage compared to laser and SRP for the treatment of chronic periodontitis. CLINICAL RELEVANCE: Adjunctive use of the oral tissue desiccant (HybenX gel) combined with SRP improved the periodontal pocket disinfection process and enhanced tissue healing devoid of adverse effects.

Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.

INTRODUCTION: Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. METHODS: We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses. RESULTS: Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E-09) and global cognitive function (p = 1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p = 4.28E-07). DISCUSSION: Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. HIGHLIGHTS: rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.

Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease.

A rare missense APOE variant (L28P; APOE*4Pittsburgh), which is present only in populations with European ancestry, has been reported to be a risk factor for late-onset Alzheimer's disease (LOAD). However, due to the complete linkage disequilibrium of L28P with APOE*4 (C112R), its independent genetic association is uncertain. The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size. In the current study, we have re-evaluated this association in a large case-control sample of 15,762 White U.S. subjects and investigated its independent effect in APOE 3/4 subjects, as L28P has been observed only in the heterozygous state of APOE*4 carriers and 3/4 is the most common genotype containing the APOE*4 allele. The heterozygous carrier frequency of L28P, all with APOE*4, was about 3-fold higher in AD cases than in cognitively intact controls (0.845% vs. 0.277%). The age- and sex-adjusted meta-analysis odds ratio (OR) was 2.87 (95% CI: 1.34 - 6.13; = 0.0066). Among APOE 3/4 subjects, age- and sex-adjusted meta-analysis OR was 1.53 (95% CI: 0.70 - 3.36; p = 0.28), indicating its effect was independent of APOE*4. The lack of statistical significance appears mainly due to the low power of 4138 subjects with the 3/4 genotype (12% power at α= 0.05) compared to the required sample of 139,088 subjects with the 3/4 genotype to detect an OR of 1.5 at α= 0.05 and 80% power. Our data suggesting that L28P has an independent genetic effect on AD risk is reinforced by earlier experimental findings showing that this mutation leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aß42 accumulation and oxidative stress. Additional functional studies in cell-based systems and animal models will help to delineate its functional significance in the etiology of AD.