Fanconi anemia (FA) is a rare genetic disease characterized by chromosomal instability and impaired DNA damage repair. FA patients develop oral squamous cell carcinoma (OSCC) earlier and more ...frequently than the general population, especially after hematopoietic stem cell transplantation (HSCT). Although evidence of an etiological role of the local microbiome and carcinogenesis has been mounting, no information exists regarding the oral microbiome of FA patients. The aim of this study was to explore the salivary microbiome of 61 FA patients regarding their oral health status and OSCC risk factors. After answering a questionnaire and receiving clinical examination, saliva samples were collected and analyzed using 16S rRNA sequencing of the V3-V4 hypervariable region. The microbial profiles associated with medical and clinical parameters were analyzed using general linear models. Patients were young (mean age, 22 y) and most had received HSCT (n = 53). The most abundant phyla were Firmicutes mean relative abundance (SD), 42.1% (10.1%) and Bacteroidetes (25.4% (11.4%). A history of graft-versus-host disease (GVHD) (n = 27) was associated with higher proportions of Firmicutes (43.8% × 38.5%, P = 0.05). High levels of gingival bleeding were associated with the genera Prevotella (22.25% × 20%), Streptococcus (19.83% × 17.61%), Porphyromonas (3.63% × 1.42%, P = 0.03), Treponema (1.02% × 0.28%, P = 0.009), Parvimonas (0.28% × 0.07%, P = 0.02) and Dialister (0.27% × 0.10%, P = 0.04). Finally, participants transplanted over 11 y ago showed the highest levels of Streptococcus (18.4%), Haemophilus (12.7%) and Neisseria (6.8%). In conclusion, FA patients that showed poor oral hygiene harbored higher proportions of the genera of bacteria compatible with gingival disease. Specific microbial differences were associated with a history of oral GVHD and a history of oral mucositis.
The effect of preventive oral habits is largely unexplored in older individuals. The purpose of this study was to evaluate the associations between home use of flossing and prevalence of periodontal ...disease and caries in older adults. Five-year incident tooth loss was also evaluated. Data on 686 individuals ≥65 y-old from the Piedmont 65+ Dental Study were examined including: 1) interproximal clinical attachment level (iCAL), 2) interproximal probing depth (iPD), 3) numbers of caries, and 4) missing teeth. Flossing behavior was evaluated according to the Periodontal Profile Class (PPC) system. Five-year follow-up data (n = 375) was evaluated for incident tooth loss. Dichotomous and categorical variables were analyzed using Pearson chi-square tests as well as covariate-adjusted Cochran-Mantel-Haenszel tests. Multiple linear regression compared clinical parameters based on flossing behavior. Elderly flossers had lower (mean, SE) %iCAL≥3 mm (38.2, 2.38 vs. 48.8, 1.56) and %iPD≥4 mm (8.70, 1.41 vs. 14.4, 0.93) compared to nonflossers (P ≤ 0.005). Flossers showed less coronal caries compared to nonflossers (P = 0.02). Baseline number of missing teeth (mean, SE) was 11.5 (0.35) in nonflossers compared to 8.6 (0.53) in flossers (P < 0.0001). Regular dental visitors had lower oral disease levels compared to episodic dental users. The majority of flossers classified into PPC-Stage I (health) whereas nonflossers classified as PPC-Stages V, VI, and VII (disease). At the 5-y follow-up visit, the average tooth loss for flossers was ~1 tooth compared to ~4 teeth lost for nonflossers (P < 0.0001). Among all teeth, molars showed the highest benefit (>40%) for flossing behavior (P = 0.0005). In conclusion, the extent of oral disease for older individuals was significantly less in flossers than in nonflossers. Flossers showed less periodontal disease, fewer dental caries, and loss of fewer teeth over a 5-y period. These findings further support flossing as an important oral hygiene behavior to prevent oral disease progression in older adults.
Background: A molecular epidemiologic study provided the opportunity to characterize the biology of the biofilm–gingival interface (BGI) in 6,768 community‐dwelling subjects.
Methods: Disease ...classifications and multivariable models were developed using clinical, microbial, inflammatory, and host‐response data. The purpose was to identify new clinical categories that represented distinct biologic phenotypes based upon DNA checkerboard analyses of eight plaque bacteria, serum immunoglobulin G (IgG) titers to 17 bacteria, and the gingival crevicular fluid (GCF) levels of 16 inflammatory mediators. Five BGI clinical conditions were defined using probing depths (PDs) and bleeding on probing (BOP) scores. Subjects with all PDs ≤3 mm were grouped as BGI‐healthy (14.3% of sample) or BGI‐gingivitis (BGI‐G, 15.1%). Subjects with one or more PDs ≥4 mm deep lesion (DL) were divided into low BOP (18.0%), moderate BOP (BGI‐DL/MB, 39.7%), and severe BOP (BGI‐DL/SB, 12.9%).
Results: Subjects with BGI‐G had increased levels of Campylobacter rectus–specific serum IgG levels (P = 0.01), and those with BGI‐DL/SB had increased IgG levels to Porphyromonas gingivalis (P < 0.0003) and C. rectus (P < 0.01). BGI‐DL/SB subjects had an excessive GCF interleukin (IL)‐1β and prostaglandin E2 response and an enhanced chronic inflammatory response with significant increases in GCF IL‐6 and monocyte chemotactic peptide‐1. Within BGI‐DL/SB subjects, more severe pocketing and BOP were associated with higher levels of GCF IL‐1β, not higher microbial counts or plaque scores.
Conclusions: New BGI classifications create categories with distinct biologic phenotypes. The increased titers of C. rectus IgG among 68.5% of the BGI‐G subjects and elevated P. gingivalis titers among BGI‐DL/MB and BGI‐DL/SB subjects (63.8% and 75.7%, respectively) are strongly supportive of the microbial specificity of pathogenesis for BGI categories.
Precise classification of periodontal disease has been the objective of concerted efforts and has led to the introduction of new consensus-based and data-driven classifications. The purpose of this ...study was to characterize the microbiological signatures of a latent class analysis (LCA)–derived periodontal stratification system, the Periodontal Profile Class (PPC) taxonomy. We used demographic, microbial (subgingival biofilm composition), and immunological data (serum IgG antibody levels, obtained with checkerboard immunoblotting technique) for 1,450 adult participants of the Dental Atherosclerosis Risk in Communities (ARIC) study, with already generated PPC classifications. Analyses relied on t tests and generalized linear models with Bonferroni correction. Men and African Americans had higher systemic antibody levels against most microorganisms compared to women and Caucasians (P < 0.05). Healthy individuals (PPC-I) had low levels of biofilm bacteria and serum IgG levels against most periodontal pathogens (P < 0.05). Subjects with mild to moderate disease (PPC-II to PPC-III) showed mild/moderate colonization of multiple biofilm pathogens. Individuals with severe disease (PPC-IV) had moderate/high levels of biofilm pathogens and antibody levels for orange/red complexes. High gingival index individuals (PPC-V) showed moderate/high levels of biofilm Campylobacter rectus and Aggregatibacter actinomycetemcomitans. Biofilm composition in individuals with reduced periodontium (PPC-VI) was similar to health but showed moderate to high antibody responses. Those with severe tooth loss (PPC-VII) had significantly high levels of multiple biofilm pathogens, while the systemic antibody response to these microorganisms was comparable to health. The results support a biologic basis for elevated risk for periodontal disease in men and African Americans. Periodontally healthy individuals showed a low biofilm pathogen and low systemic antibody burden. In the presence of PPC disease, a microbial-host imbalance characterized by higher microbial biofilm colonization and/or systemic IgG responses was identified. These results support the notion that subgroups identified by the PPC system present distinct microbial profiles and may be useful in designing future precise biological treatment interventions.
This longitudinal cohort study examines if 1) cognitive decline varies by birth cohort, adjusting for covariates, and 2) edentulism and nonuse of dental care predict 10-y cognitive decline ...(2008–2018). The Health and Retirement Study (HRS) features a representative sample of US adults over age 50. Eligibility criteria included having cognitive interview data available and responding to the question, “Have you lost all of your upper and lower natural permanent teeth?” at 2+ time points between 2006 and 2018. Use of dental care in the past 2 y was assessed. Linear mixed models for repeated measures estimated the trajectories of mean cognition over time for the birth cohorts, adjusted for baseline cognition, dentition status, dental care use, and covariates (demographic characteristics, health behaviors, and medical conditions). Cohort-by-time interaction terms were included to assess if cognitive decline varied by birth cohort. Ten-year change in cognition status (measured by HRS Cogtot27)—categorized as dementia (<7); cognitive impairment, not demented (7-11) 7≤Cogtot27<12; and normal (≥12)—was also investigated according to birth cohort, dentition status, and dental care use. Mean (SD) baseline age was 63.4 (10.1) y (n = 22,728). Older birth cohorts had greater cognitive decline than younger cohorts. Linear mixed-model estimates and 95% confidence intervals for protective factors for cognitive decline included higher baseline cognition (HRS Cogtot27) (0.49; 0.48–0.50), use of dental care in the past 2 y (0.17; 0.10–0.23), and covariates such as greater household wealth and being married. Risk increased with being edentulous (−0.42; −0.56 to −0.28), history of stroke or diabetes, less education, Medicaid recipient, current smoker, loneliness, and poor/fair self-rated health. Edentulism and irregular dental care are among important predictors of cognitive decline. Tooth retention and regular dental care throughout life appear to be important for maintaining oral and cognitive health.
Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting ...structures. One such genetic locus was the tumor necrosis factor receptor–associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)–17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17–mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2–/–) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis–induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2–/– mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2–/– mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2–/– mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2–/– mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.
High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its ...sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant.
A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering.
169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren–Lawrence measured progression (RR = 1.55 0.56.4.32), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 0.01.0.89 and 0.15 0.01.0.29, respectively). HBM individuals had higher WOMAC knee pain scores (β = 7.42 1.17.13.66), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation.
HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.
One of the longest-lived, noncolonial animals on the planet today is a bivalve that attains life spans in excess of 500 years and lives in a cold, seasonally food-limited setting. Separating the ...influence of temperature and food availability on life span in modern settings is difficult, as these two conditions covary. The life spans of fossil animals can provide insights into the role of environment in the evolution of extreme longevity that are not available from studies of modern taxa. We examine bivalves from the unique, nonanalogue, warm and high-latitude setting of Seymour Island, Antarctica, during the greenhouse intervals of the Late Cretaceous and Paleogene. Despite significant sampling limitations, we find that all 11 species examined are both slow growing and long-lived, especially when compared with modern bivalves living in similar temperature settings. While cool temperatures have long been thought to be a key factor in promoting longevity, our findings suggest an important role for caloric restriction brought about by the low and seasonal light regime of the high latitudes. Our life-history data, spanning three different families, emphasize that longevity is in part governed by environmental rather than solely phylogenetic or ecologic factors. Such findings have implications for both modern and ancient latitudinal diversity gradients, as a common correlate of slow growth and long life is delayed reproduction, which limits the potential for evolutionary change. While life spans of modern bivalves are well studied, data on life spans of fossil bivalves are sparse and largely anecdotal. Life histories of organisms from deep time can not only elucidate the controls on life span but also add a new dimension to our understanding of macroevolutionary patterns.
Inclusive education is now advocated as best practice in schools. However, the extent to which adolescents with severe disabilities access the abundant social and academic experiences available in ...general education classes remains uncertain. We conducted multiple observations of 146 U.S. high school students with severe disabilities (including intellectual disability, autism, or multiple disabilities), who were enrolled in at least one general education class. Peer interactions with classmates tended to be very infrequent for most students with severe disabilities. Moreover, rates of peer interaction were the lowest during large-group instruction and when students were sitting next to paraprofessionals or special educators rather than with their peers. Academic engagement also varied across students and was highest during small-group instruction, during 1-on-1 work with adults, and when students sat near their peers. Observations of a comparison sample of peers attending these same classes revealed striking overall differences in social and academic participation. We offer recommendations for research and practice aimed at bolstering inclusive education in high schools.
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