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1. Oral Candida Predicts Streptococcus mutans Emergence in Underserved US Infants

   https://doi.org/10.1177/00220345211012385  

   Alkhars, N. ; Zeng, Y. ; Alomeir, N. ; Al Jallad, N. ; Wu, T.T. ; Aboelmagd, S. ; Youssef, M. ; Jang, H. ; Fogarty, C. ; Xiao, J. ( January 2021 , Journal of Dental Research)

   null (Ed.)

   Despite the cariogenic role of Candida suggested from recent studies, oral Candida acquisition in children at high risk for early childhood caries (ECC) and its association with cariogenic bacteria Streptococcus mutans remain unclear. Although ECC disproportionately afflicts socioeconomically disadvantaged and racial-minority children, microbiological studies focusing on the underserved group are scarce. Our prospective cohort study examined the oral colonization of Candida and S. mutans among 101 infants exclusively from a low-income and racial-minority background in the first year of life. The Cox hazard proportional model was fitted to assess factors associated with the time to event of the emergence of oral Candida and S. mutans. Oral Candida colonization started as early as 1 wk among 13% of infants, increased to 40% by 2 mo, escalated to 48% by 6 mo, and remained the same level until 12 mo. S. mutans in saliva was detected among 20% infants by 12 mo. The emergence of S. mutans by year 1 was 3.5 times higher (hazard ratio [HR], 3.5; confidence interval [CI], 1.1–11.3) in infants who had early colonization of oral Candida compared to those who were free of oral Candida ( P = 0.04) and 3 times higher (HR, 3.0; CI, 1.3–6.9) among infants whose mother had more than 3 decayed teeth ( P = 0.01), even after adjusting demographics, feeding, mother’s education, and employment status. Infants’ salivary S. mutans abundance was positively correlated with infants’ Candida albicans ( P < 0.01) and Candida krusei levels ( P < 0.05). Infants’ oral colonization of C. albicans was positively associated with mother’s oral C. albicans carriage and education ( P < 0.01) but negatively associated with mother’s employment status ( P = 0.01). Future studies are warranted to examine whether oral Candida modulates the oral bacterial community as a whole to become cariogenic during the onset and progression of ECC, which could lead to developing novel ECC predictive and preventive strategies from a fungal perspective. 

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2. Metagenomic analysis examines oral microbiome changes and interplay with immune response following prenatal total oral rehabilitation

   https://doi.org/10.1186/s12967-023-03997-9  

   Wu, Tong Tong ; Sohn, Michael ; Manning, Samantha ; Beblavy, Robert ; Gill, Steven ; Quataert, Sally ; Vasani, Shruti ; Jang, Hoonji ; Zeng, Yan ; Bruno, Jennifer ; et al ( December 2023 , Journal of Translational Medicine)

   Suboptimal maternal oral health during pregnancy is potentially associated with adverse birth outcomes and increased dental caries risks in children. This study aimed to assess the oral microbiome and immune response following an innovative clinical regimen, Prenatal Total Oral Rehabilitation (PTOR), that fully restores women’s oral health to a “disease-free status” before delivery.

   This prospective cohort study assessed 15 pregnant women at baseline and 3 follow-up visits (1 week, 2 weeks, and 2 months) after receiving PTOR. The salivary and supragingival plaque microbiomes were analyzed using metagenomic sequencing. Multiplexed Luminex cytokine assays were performed to examine immune response following PTOR. The association between salivary immune markers and oral microbiome was further examined.

   PTOR was associated with a reduction of periodontal pathogens in plaque, for instance, a lower relative abundance ofTannerella forsythiaandTreponema denticolaat 2 weeks compared to the baseline (p < 0.05). The alpha diversity of plaque microbial community was significantly reduced at the 1-week follow-up (p < 0.05). Furthermore, we observed significant changes in theActinomyces defective-associated carbohydrate degradation pathway andStreptococcus Gordonii-associated fatty acid biosynthesis pathway. Two immune markers related to adverse birth outcomes significantly differed between baseline and follow-up. ITAC, negatively correlated with preeclampsia severity, significantly increased at 1-week follow-up; MCP-1, positively correlated with gestational age, was elevated at 1-week follow-up. Association modeling between immune markers and microbiome further revealed specific oral microorganisms that are potentially correlated with the host immune response.

   PTOR is associated with alteration of the oral microbiome and immune response among a cohort of underserved US pregnant women. Future randomized clinical trials are warranted to comprehensively assess the impact of PTOR on maternal oral flora, birth outcomes, and their offspring’s oral health.

    

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3. Factors associated with the counts of selected oral microorganisms in nursing home residents

   https://doi.org/10.1111/scd.12530  

   Wenger, Kelsey ; Pendleton, Chandler ; Xie, Xian Jin ; Caplan, Daniel J. ; Drake, David ; Marchini, Leonardo ( October 2020 , Special Care in Dentistry)

   To analyze potential factors associated with levels of selected oral pathogens, as well as total aerobic bacterial species, among nursing home residents.

   Nursing home residents were divided into three groups (G1 included people with teeth but no dentures, G2 included people with teeth and dentures, and G3 included people with no teeth and with dentures). All participants had microbiological samples collected from their oral cavity and dentures. Counts of total aerobic bacterial species,Porphyromonas gingivalis,Fusobacterium nucleatum,Actinomyces viscosus,Aggregatibacter actinomycetemcomitans, andCandida albicanswere compared among groups using the Wilcoxon rank sum test. A multivariate analysis was also performed to control other available covariates.

   Bivariate analysis revealed significant differences among the groups, and multivariate analysis showed that sex, the presence of natural teeth, denture wearing, oral hygiene indices, and systemic health conditions were associated with bacterial andCandida albicanslog counts.

   Presence of natural teeth and denture wearing, as well as oral hygiene, sex and systemic health conditions were associated with bacterial andCandida albicanslog counts among nursing home residents.

    

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4. Modeling Oral Multispecies Biofilm Recovery After Antibacterial Treatment

   https://doi.org/10.1038/s41598-018-37170-w  

   Jing, Xiaobo ; Huang, Xiangya ; Haapasalo, Markus ; Shen, Ya ; Wang, Qi ( January 2019 , Scientific Reports)

   Recovery of multispecies oral biofilms is investigated following treatment by chlorhexidine gluconate (CHX), iodine-potassium iodide (IPI) and Sodium hypochlorite (NaOCl) both experimentally and theoretically. Experimentally, biofilms taken from two donors were exposed to the three antibacterial solutions (irrigants), respectively, for 10 minutes. We observe that (a) live bacterial cell ratios decline for a week after the exposure and the trend then reverses beyond the week; after fifteen weeks, live bacterial cell ratios in biofilms fully return to their pretreatment levels; (b) NaOCl is shown as the strongest antibacterial agent for the oral biofilms; (c) multispecies oral biofilms from different donors showed no difference in their susceptibility to all the bacterial solutions. Guided by the experiment, a mathematical model for biofilm dynamics is developed, accounting for multiple bacterial phenotypes, quorum sensing, and growth factor proteins, to describe the nonlinear time evolutionary behavior of the biofilms. The model captures time evolutionary dynamics of biofilms before and after antibacterial treatment very well. It reveals the important role played by quorum sensing molecules and growth factors in biofilm recovery and verifies that the source of biofilms has a minimal effect to their recovery. The model is also applied to describe the state of biofilms of various ages treated respectively by CHX, IPI and NaOCl, taken from different donors. Good agreement with experimental data predicted by the model is obtained as well, confirming its applicability to modeling biofilm dynamics in general.

    

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5. Micro-calcifications predict plaque vulnerability and initiate rupture of the fibrous cap

   Corti A ; Dinh A ; De Paolis A ; Aikawa E ; Weinbaum S ; Cardoso L. ( April 2022 , 48th Annual Northeast Bioengineering Conference (NEBEC 2022))

   Introduction: The mechanical stability of an atheroma fibrous cap (FC) is a crucial factor for the risk of heart attack or stroke in asymptomatic vulnerable plaques. Common determinants of plaque vulnerability are the cap thickness and the presence of micro-calcifications (µCalcs). Higher local stresses have been linked to thin caps(<65µm) and, more recently, our lab demonstrated how µCalcs can potentially initiate cap rupture [1-3]. When combined, these two factors can compromise to a greater extent the stability of the plaque. On this basis, we quantitatively analyzed both individual and combined effects of key determinants of plaque rupture using a tissue damage model on idealized atherosclerotic arteries. Our results were then tested against a diseased human coronary sample. Methods: We performed 28 finite element simulations on three-dimensional idealized atherosclerotic arteries and a human coronary sample. The idealized models present 10% lumen narrowing and 1.25 remodeling index (RI)(Fig.1A). The FC thickness values that we considered were of 50, 100, 150 and 200µm. The human coronary presents a RI=1.31, with 31% lumen occlusion and a 140µm-thick cap(Fig.1B). The human model is based on 6.7μm high-resolution microcomputed tomography (HR-μCT) images. The µCalc has a diameter of 15µm and each artery was expanded up to a systolic pressure of 120mmHg. Layer-specific material properties were de-fined by the HGO model coupled with the hyperelastic failure description proposed by Volokh et al. [4] to repli-cate the rupture of the FC. We considered a max. princi-pal stress for rupture of 545kPa[5]. The lipid core and the µCalc were considered as elastic materials (Ecore = 5kPa, νcore = 0.49; EµCalc= 18,000 kPa, νµCalc=0.3). To obtain a detailed analysis of the cap stresses and rupture progres-sion, a sub-modeling approach was implemented using ABAQUS (Dassault Systemes, v.2019) (Fig. 1). Results: We investigated the quantitative effect of cap thickness and µCalc by simulating tissue failure and de-riving a vulnerability index (VI) for each risk factor. The VI coefficient was defined as the peak cap stress (PCS) normalized by the threshold stress for rupture (545kPa). The relationship between the risk factors and VI was de-termined by deriving the Pearson’s correlation coefficient (PCC) followed by one-tailed t-test (SPSS, IBM, v.25). The null hypothesis was rejected if p<0.05. The presence of the µCalc is the factor that manifests the greater impact on cap stability, leading to at least a 2.5-fold increase in VI and tissue rupture regardless of cap thickness (Fig.2A,B). One µCalc in the cap is the first predictor of vulnerability, with PCCµCalc=0.59 and pµCalc=0.001. Our results also confirm the substantial in-fluence of cap thickness, with an exponential increase in stresses as the cap becomes thinner. The 50µm cap is the only phenotype that ruptures without µCalc (Fig2A). The human sample exhibits PCS levels that are close to the idealized case with 150µm cap and it doesn’t rupture in the absence of the µCalc (PCShuman=233kPa, PCSideal= 252kPa). Conversely, the phenotypes with the µCalc showed an increase in VI of about 2.5 and reached rup-ture under the same blood pressure regime. Conclusions: Our results clearly show the multifactorial nature of plaque vulnerability and the significance of micro-calcifications on the cap mechanical stability. The presence of a μCalc strongly amplifies the stresses in the surrounding tissue, and it can provoke tissue failure even in thick caps that would otherwise be classified as stable. Clearly, plaque phenotypes with a thin cap and μCalcs in the tissue represent the most vulnerable condition. Finally, these observations are well validated by the case of the human atherosclerotic segment, which closely compares to its corresponding idealized model. The novel imple-mentation of the tissue damage description and the defi-nition of a vulnerability index allow one to quantitatively analyze the individual and combined contribution of key determinants of cap rupture, which precedes the for-mation of a thrombus and myocardial infarction. 

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