Salivary levels of MPO, MMP-8 and TIMP-1 are associated with gingival inflammation response patterns during experimental gingivitis

Aim: This study aimed to investigate the association between salivary levels of myeloperoxidase (MPO), neutrophil elastase (NE), soluble urokinase-type plasminogen activator receptor (suPAR), matrix metalloproteinase (MMP)-8 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and gingival inflammation development during an experimental gingivitis study. Methods: A three-week experimental gingivitis study was conducted. Clinical recordings of dental plaque biofilm (Modified Quigley Hein Plaque Index, TQHPI) and gingival inflammation (Modified Gingival Index, MGI) were made at specific time points for each of the 42 participants. Salivary levels of MPO, NE, suPAR, MMP-8 and TIMP-1 at the same time points were measured using distinct immunoassays. For data analysis growth curve modelling was employed to account for the time-varying outcome (MGI score) and the time-varying covariates (salivary marker levels, and TQHPI score). Analyses were stratified according to the MGI-score trajectory groups previously identified as 'fast', respectively 'slow' responders. Results: Overall, higher MGI scores were statistically significantly positively associated with higher levels of MPO, MMP-8 and TIMP-1. Stratified analysis according to inflammation development trajectory group revealed higher levels of salivary MPO, MMP-8 and MMP-8/TIMP-1 ratio among the 'fast' responders than among 'slow' responders. None of the investigated salivary protein markers was associated with a 'slow' inflammation development response. Conclusions: Salivary levels of MPO, MMP-8 and TIMP-1 were associated with the extent and severity of gingival inflammation. While the 'fast' gingival inflammation response was associated with increased levels of MPO, MMP-8 and MMP-8/TIMP-1 ratio, the 'slow' response was not associated with any of the salivary protein markers investigated in this study. Neutrophil activity seems to orchestrate a 'fast' gingival inflammatory response among participants previously primed to gingival inflammation.Peer reviewe

Comparison of fusobacterium nucleatum and porphyromonas gingivalis lipopolysaccharides clinically isolated from root canal infection in the induction of pro-inflammatory cytokines secretion

The aim of this study was to compare the biological activity of lipopolysaccharides (LPS) purified from Fusobacterium nucleatum and Porphyromonas gingivalis strains, both isolated from primary endodontic infection (PEI) in the levels of IL-1β and TNF-α released by macrophage cells. Moreover, LPS was purified from F. nucleatum and P. gingivalis American Type Collection (ATCC) and its biological activity was compared to respectively clinical isolates strains. F. nucleatum and P. gingivalis strains clinically isolated from PEI had their identification confirmed by sequencing the 16S rRNA gene. LPS from F. nucleatum and P. gingivalis and their respective ATCC strains were extracted by using Tri-reagent method. Macrophages (Raw 264.7) were stimulated with LPS at 100 ng/mL for 4, 8 and 12 h. Secretion of IL-1 β and TNF-α was also determined. Paired t-test, repeated measures ANOVA and one-way ANOVA were employed. All LPS induced significant production of IL-1β and TNF-α, with the former being secreted at higher levels than the latter in all time-points. F. nucleatum induced a higher expression of both cytokines compared to P. gingivalis (p<0.05). No differences were observed between clinical and ATCC strains, as both presented the same potential to induce pro-inflammatory response. It was concluded that F. nucleatum and P. gingivalis LPS presented different patterns of activation against macrophages as seen by the IL-1β and TNF-α production, which may contribute to the immunopathogenesis of apical periodontitis. Moreover, clinical and ATCC strains grown under the same in vitro environment conditions presented similar biological activity272202207CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP302575/2009-0; 150557/2011-6; 308162/2014-510/19136-1; 10/17877- 4; 11/50051-5; 11/50510-0; 11/09047-4O objetivo deste estudo foi comparar a atividade biológica de lipopolissacarídeos (LPS) purificados a partir de linhagens de Fusobacterium nucleatum e Porphyromonas gingivalis, ambas isoladas de infecções endodônticas primárias (IEP) nos níveis de IL-1β e TNF-α produzidos por macrófagos. Adicionalmente, LPS foi purificado de F. nucleatum e P. gingivalis "American Type Collection" (ATCC) e sua atividade comparada às respectivas linhagens clinicamente isoladas. Linhagens de F. nucleatum e P. gingivalis isoladas clinicamente de IEP tiveram sua identificação confirmada por sequenciamento do gene 16S rRNA. LPS de F. nucleatum e P. gingivalis e das respectivas linhagens foram extraídos com o uso do método "Tri-reagent". Macrófagos (Raw 264.7) foram estimulados com LPS a 100 ng/mL por 4, 8 e 12 h. A secreção de IL-1β e de TNF-α foi determinada. Foram usados os testes t-pareado, ANOVA de medidas repetidas e ANOVA de um fator. Todos os LPS induziram a produção significante de IL-1β e TNF-α, sendo o primeiro secretado em mais altas concentrações que o último em todos os tempos avaliados. F. nucleatum induziu uma maior expressão de ambas as citocinas comparativamente ao P. gingivalis (p<0,05). Não foram observadas diferenças entre as linhagens clínica e ATCC, uma vez que ambas apresentaram o mesmo potencial de indução da resposta pró-inflamatória. Conclui-se que F. nucleatum e P. gingivalis possuem diferentes padrões de ativação dos macrófagos, como visto pela produção de IL-1β e TNF-α, o que pode contribuir para a imunopatogênese da periodontite apical. Ainda, linhagens clínica e ATCC mantidas no mesmo ambiente in vitro apresentaram ativação biológica semelhant

Federated and distributed learning applications for electronic health records and structured medical data: A scoping review

Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations and discusses potential innovations. We searched five databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from three primary perspectives, including data quality, modeling strategies, and FL frameworks. Out of the 1160 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research

Thyroid hormone response element organization dictates the composition of active receptor

Thyroid hormone (triiodothyronine, T3) is known to activate transcription by binding heterodimers of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs). RXR-TRs bind to T3 response elements (TREs) composed of direct repeats of the sequence AGGTCA spaced by four nucleotides (DR-4). In other TREs, however, the half-sites can be arranged as inverted palindromes and palindromes (Pal). Here we show that TR homodimers and monomers activate transcription from representative TREs with alternate half-site placements. TRβ activates transcription more efficiently than TRα at an inverted palindrome (F2), and this correlates with preferential TRβ homodimer formation at F2 in vitro. Furthermore, reconstruction of TR transcription complexes in yeast indicates that TRβ homodimers are active at F2, whereas RXR-TRs are active at DR-4 and Pal. Finally, analysis of TRβ mutations that block homodimer and/or heterodimer formation reveal TRE-selective requirements for these surfaces in mammalian cells, which suggest that TRβ homodimers are active at F2, RXR-TRs at DR-4, and TR monomers at Pal. TRβ requires higher levels of hormone for activation at F2 than other TREs, and this differential effect is abolished by a dimer surface mutation suggesting that it is related to composition of the TR·TRE complex. We propose that interactions of particular TR oligomers with different elements play unappreciated roles in TRE-selective actions of liganded TRs in vivo

Salivary Total Protease Activity Based on a Broad-Spectrum Fluorescence Resonance Energy Transfer Approach to Monitor Induction and Resolution of Gingival Inflammation

OBJECTIVE: Salivary total protease and chitinase activities were measured by a broad-spectrum fluorescence resonance energy transfer approach as predictors of induction and resolution of gingival inflammation in healthy individuals by applying an experimental human gingivitis model. METHODS: Dental biofilm accumulated (21 days, Induction Phase) by omitting oral hygiene practices followed by a 2-week Resolution Phase to restore gingival health in an experimental gingivitis study. Plaque accumulation, as assessed by the Turesky Modification of the Quigley-Hein Plaque Index (TQHPI), and gingival inflammation, assessed using the Modified Gingival Index (MGI), scores were recorded and unstimulated saliva was collected weekly. Saliva was analysed for total protein, albumin, total protease activity and chitinase activity (n = 18). RESULTS: The TQHPI and MGI scores, as well as total protease activity, increased until day 21. After re-establishment of oral hygiene, gingival inflammation levels returned to values similar to baseline (day 0). Levels of protease activity decreased significantly, but not to baseline values. Furthermore, 'fast' responders, who responded immediately to plaque, exhibited significantly higher proteolytic activity throughout the experimental course than 'slow' responders, who showed a lagged inflammatory response. CONCLUSION: The results indicate that differential inflammatory responses encompass inherent variations in total salivary proteolytic activities, which could be further utilised in contemporary diagnostic, prognostic and treatment modalities for periodontal diseases

Dental caries in Uruguayan adults and elders: findings from the first Uruguayan National Oral Health Survey

This study aimed to assess dental caries status and associated factors in Uruguayan adults and elders using data from the first Uruguayan National Oral Health Survey. Data were representative of the country as a whole. Socio-demographic information was collected with a closed questionnaire. Dental caries was assessed by clinical examination using the DMFT index. The final sample consisted of 769 participants. Mean DMFT was 15.20 and 24.12 for the 35-44 and 65-74-year age groups, respectively. Mean number of decayed teeth was 1.70 in adults and 0.66 in elders. Multivariate analyses showed higher prevalence of dental caries associated with age 65-74 years, low socioeconomic status, use of public dental services, presence of gingivitis; for decayed teeth, age 35-44 years, low socioeconomic status, use of public dental services, infrequent tooth brushing, need for oral health care, and presence of root caries showed higher severity. Uruguayan adults and elders from disadvantaged backgrounds concentrated a heavier burden of dental caries

Applying the Maternal Near Miss Approach for the Evaluation of Quality of Obstetric Care: A Worked Example from a Multicenter Surveillance Study

Objective. To assess quality of care of women with severe maternal morbidity and to identify associated factors. Method. This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. the expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. Results. 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (P < 0.001), delays related to quality of medical care (P = 0.012), absence of blood derivatives (P = 0.013), difficulties of communication between health services (P = 0.004), and any delay during the whole process (P = 0.039). Conclusions. This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. in this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Campinas UNICAMP, Sch Med Sci, Dept Obstet & Gynaecol, BR-13083881 Campinas, SP, BrazilCtr Res Reprod Hlth Campinas Cemicamp, BR-13083888 Campinas, SP, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilSch Med Sci, CISAM, Recife, PE, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilUniv Fed Bahia, Salvador, BA, BrazilHosp Geral Cesar Cals, Fortaleza, Ceara, BrazilHosp Geral Fortaleza, Fortaleza, Ceara, BrazilMaternidade Odete Valadares, Belo Horizonte, MG, BrazilHosp Materno Infantil, Goiania, Go, BrazilInst Materno Infantil Pernambuco, Recife, PE, BrazilUniv Fed Pernambuco, Recife, PE, BrazilUniv Fed Campina Grande, Campina Grande, PB, BrazilUniv Fed Maranhao, Sao Luis, MA, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Paraiba, BR-58059900 Joao Pessoa, Paraiba, BrazilHosp Maternidade Fernando Magalhaes, Rio de Janeiro, RJ, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilHosp Maternidade Celso Pierro, Campinas, SP, BrazilInst Fernandes Figueira Fiocruz, Rio de Janeiro, RJ, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv State São Paulo, Botucatu, SP, BrazilJundiai Sch Med, Jundiai, SP, BrazilUniv São Paulo, BR-14049 Ribeirao Preto, SP, BrazilSanta Casa Limeira, Limeira, SP, BrazilSanta Casa Sao Carlos, Sao Carlos, SP, BrazilMaternidade Leonor Mendes de Barros, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilCNPq: 402702/2008-5Web of Scienc