RESUMEN
INTRODUCTION: Periodontitis, as a chronic, multifactorial inflammatory disease, has complex relationships with other diseases and ultimately with well-being. The aim of this cross-sectional study was to investigate the association between self-report periodontitis, as measured with the recently developed and validated modified Periodontal Screening Score (mPESS), and oral health-related quality of life (OHRQol) in a large population-based sample derived from the French NutriNet-Santé e-cohort. METHODS: The sample was composed of 32,714 adults (75.5% women) with a mean age of 48.8 ± 13.9 years. Periodontitis was assessed based on age, smoking, and oral health status data obtained in 2011-2012, which allowed calculating the mPESS. An mPESS ≥ 5 was used to identify individuals at risk of severe periodontitis (main exposure). OHRQoL was measured with the Oral Health Impact Profile (OHIP-14) (main outcome) and the total score was dichotomized for analysis. Multivariable logistic regression analyses, considering physical health status, dietary and lifestyle confounding variables, were performed. RESULTS: Overall, 6407 participants (19.6%) were at a high risk of severe periodontitis. A total of 7383 participants (22.6%) presented a relatively poor OHRQoL (OHIP-14 > 8, highest quartile). In the multivariable model, each of the following variables was independently and significantly associated with lower OHRQoL: older age (50-64 years), female sex, obesity, snacking between meals, frequent consumption of soft drinks and sweets/chocolate, risk of severe periodontitis, and having < 20 natural teeth were significantly. An mPESS ≥ 5 showed the highest odds for relatively poor OHRQoL (OR = 3.45; 95% CI 3.21-3.72). CONCLUSION: The results support the association between periodontitis and OHRQoL in non-clinical samples. The use of mPESS could be tested in future prevention programs aiming at improving OHRQoL.
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Periodontitis , Calidad de Vida , Humanos , Adulto , Femenino , Persona de Mediana Edad , Masculino , Calidad de Vida/psicología , Estudios Transversales , Salud Bucal , Periodontitis/epidemiología , Estado de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Baloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence. METHODS: Influenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR. RESULTS: I38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50%:50% mixture evolved to 70%:30% (WT/mutant) for A(H1N1) and 88%:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments. CONCLUSION: The fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.
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Antivirales/farmacología , Farmacorresistencia Viral/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Oxazinas/farmacología , Piridinas/farmacología , ARN Polimerasa Dependiente del ARN/genética , Tiepinas/farmacología , Triazinas/farmacología , Proteínas Virales/genética , Sustitución de Aminoácidos , Animales , Antivirales/uso terapéutico , Dibenzotiepinas , Perros , Femenino , Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Subtipo H3N2 del Virus de la Influenza A/enzimología , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Concentración 50 Inhibidora , Pulmón/virología , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos C57BL , Morfolinas , Mutación , Infecciones por Orthomyxoviridae/virología , Oxazinas/uso terapéutico , Fenotipo , Piridinas/uso terapéutico , Piridonas , ARN Polimerasa Dependiente del ARN/metabolismo , Tiepinas/uso terapéutico , Triazinas/uso terapéutico , Carga Viral/efectos de los fármacos , Proteínas Virales/metabolismo , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Recent evidence suggests that dietary habits influence the development and severity of periodontitis. The present cross-sectional study evaluated the association between different types and quantity of alcoholic beverage consumption (alone and interacting with smoking) and the probability to suffer from severe periodontitis in the French e-cohort NutriNet-Santé. METHODS: The study population consisted of 35,390 adults (mean age: 49.04 ± 13.94 years), who filled oral health questionnaires and completed at least three non-consecutive 24-hour dietary records. Data on type and frequency of alcoholic beverage consumption were obtained from a semi-quantitative self-reported alcohol frequency questionnaire; the daily quantity (g/day) was estimated from the 24-hour dietary records. The probability of severe periodontitis (main dependent variable) was assessed by calculating the modified periodontal screening score (mPESS) from selected questions. RESULTS: A total of 7263 individuals (20.5%) presented a high probability of suffering from severe periodontitis (high-mPESS). After adjusting for confounding factors, the frequency of alcoholic beverage consumption was significantly higher among high-mPESS group than their low-mPESS counterparts, especially for hard liquor/spirits (1.9 ± 1.4 days/week for high-PESS versus 1.6 ± 1.1 days/week the low-PESS [P < 0.0001]). The mean daily quantity of ethanol was also higher in high-mPESS versus low-mPESS individuals (11.2 ± 15.6 versus 7.9 ± 12.3 g/day; P = 0.011). A stronger association with self-report severe periodontitis was noted when alcohol consumption exceeding > 20 g/day for women and > 30 g/day for men was combined with smoking habit (OR = 7.30 [95% CI: 6.1-8.73]). CONCLUSION: The present results support an association between alcoholic beverage consumption and self-report severe periodontitis, particularly when it is associated with current smoking.
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Consumo de Bebidas Alcohólicas , Periodontitis , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/epidemiología , Periodontitis/etiología , FumarRESUMEN
The mouse is the most widely used animal model for influenza virus research. However, the susceptibility of mice to seasonal influenza virus depends on the strain of mouse and on the strain of the influenza virus. Seasonal A/H3N2 influenza viruses do not replicate well in mice and therefore they need to be adapted to this animal model. In this study, we generated a mouse-adapted A/H3N2 virus (A/Switzerland/9715293/2013 [MA-H3N2]) by serial passaging in mouse lungs that exhibited greater virulence compared to the wild-type virus (P0-H3N2). Seven mutations were found in the genome of MA-H3N2: PA(K615E), NP(G384R), NA(G320E) and HA(N122D, N144E, N246K, and A304T). Using reverse genetics, two synergistically acting genes were found as determinants of the pathogenicity in mice. First, the HA substitutions were shown to enhanced viral replication in vitro and, second, the PA-K615E substitution increased polymerase activity, although did not alter virus replication in vitro or in mice. Notably, single mutations had only limited effects on virulence in vitro. In conclusion, a co-contribution of HA and PA mutations resulted in a lethal mouse model of seasonal A/H3N2 virus. Such adapted virus is an excellent tool for evaluation of novel drugs or vaccines and for study of influenza pathogenesis.