Effie Ioannidou

Oral Candida infection and colonization in solid organ transplant recipients

INTRODUCTION Oral Candida carriage and infection have been reported to be associated with a greater risk for systemic infection in transplant recipients; however, a systematic analysis of the oral Candida titers and species has not been previously conducted. The objectives of this study were to determine the prevalence of oropharyngeal candidiasis, the oral carrier status, Candida titers and species in this population. METHODS Ninety kidney and heart transplant subjects and 72 age-matched healthy controls were included. Swabs from the oral mucosa and a standardized amount of unstimulated saliva were plated on Chromagar Candida, and colony-forming units per millilitre were calculated. Initial speciation was based on colony color and was confirmed by standard germ tube, biotyping, or polymerase chain reaction assays. RESULTS Infection with C. albicans was detected in seven transplant subjects and none of the controls. The transplant group had significantly higher oral Candida titers than the control group. There were no statistically significant relationships between the dose or type of immunosuppressants and oral Candida titers or infection. A significantly higher percentage of transplant subjects were colonized by more than one species, compared with control subjects. The most frequent species combination in transplant subjects was C. albicans and C. glabrata. C. glabrata was isolated from 13.5% of transplant carriers and none of the controls. CONCLUSIONS Increased oral Candida infection and carriage titers were found in the transplant population. Although the majority of transplant patients were colonized by C. albicans, C. glabrata appears to emerge as the second most prevalent species.

Disparities in Periodontitis Prevalence among Chronic Kidney Disease Patients

Because of adverse effects of uremia in the innate and adaptive immune systems, we hypothesized that chronic kidney disease (CKD) patients would have higher prevalence of moderate periodontitis compared with individuals without CKD. We examined this hypothesis using the NHANES III dataset, including 12,081 adults stratified by Race-Ethnicity. We followed the American Academy of Periodontology/Centers for Disease Control and Prevention definition for moderate periodontitis. Estimated glomerular filtration rate (GFR) was calculated based on calibrated serum creatinine levels according to the Modification of Diet in Renal Disease Study formula. Analyses incorporated NHANES sampling weights. Overall, 14.6% of individuals with CKD were classified as having moderate periodontitis, compared with 8.7% in the non-CKD group (p = 0.001). A significant dose-response association (p = 0.001) was observed between prevalence of moderate periodontitis and CKD stages among non-Hispanic Blacks and Mexican-Americans, but not so for non-Hispanic Whites. Prevalence of periodontitis among participants with CKD was substantially higher among non-Hispanic Blacks (38.9%) and Mexican-Americans (37.3%) compared with non-Hispanic Whites (12.9%). Multivariate logistic regression models showed that Mexican-Americans and non-Hispanic Blacks with CKD were approximately 30% to 60% more likely to have moderate periodontitis compared with those without CKD, after adjustment for diabetes status and other potential confounders.

Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome

ABSTRACT Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome.

Periodontitis Predicts Elevated C-reactive Protein Levels in Chronic Kidney Disease

Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73m2 and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).

Microbiome Profiles in Periodontitis in Relation to Host and Disease Characteristics

Periodontitis is an inflammatory condition that affects the supporting tissues surrounding teeth. The occurrence of periodontitis is associated with shifts in the structure of the communities that inhabit the gingival sulcus. Although great inter-subject variability in the subgingival microbiome has been observed in subjects with periodontitis, it is unclear whether distinct community types exist and if differences in microbial signatures correlate with host characteristics or with the variable clinical presentations of periodontitis. Therefore, in this study we explored the existence of different community types in periodontitis and their relationship with host demographic, medical and disease-related clinical characteristics. Clustering analyses of microbial abundance profiles suggested two types of communities (A and B) existed in the 34 subjects with periodontitis evaluated. Type B communities harbored greater proportions of certain periodontitis-associated taxa, including species historically associated with the disease, such as Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, and taxa recently linked to periodontitis. In contrast, subjects with type A communities had increased proportions of different periodontitis-associated species, and were also enriched for health-associated species and core taxa (those equally prevalent in health and periodontitis). Periodontitis subgingival clusters were not associated with demographic, medical or disease-specific clinical parameters other than periodontitis extent (proportion of sites affected), which positively correlated with the total proportion of cluster B signature taxa. In conclusion, two types of microbial communities were detected in subjects with periodontitis. Host demographics and underlying medical conditions did not correlate with these profiles, which instead appeared to be related to periodontitis extent, with type B communities present in more widespread disease cases. The two identified periodontitis profiles may represent distinct dysbiotic processes potentially requiring community-tailored therapeutic interventions.

Twelve-year follow-up of an autogenous mandibular canine transplant

Transplantation is the transfer of tissue or an organ from 1 site to another in the same person or between different persons. A transplantation in which donor and recipient are the same individual has been termed autogenous transplantation, autoplastic transplantation, or autotransplantation. The purpose of this report was to describe a patient undergoing autotransplantation of an impacted mandibular canine to its normal position in the mandible and the 12-year follow-up. Five years after the surgical procedure, the patient presented with pulp canal obliteration in the autotransplanted tooth. Twelve years after the autotransplantation, the tooth position was stable despite pulp canal obliteration, but with no sign of inflammatory resorption or a periapical lesion. In addition, there was no sign of replacement resorption (ankylosis). The endodontic literature has shown that the prognosis of patients undergoing autotransplantation may be good under specific considerations. Therefore, the technique may be a treatment plan option for the replacement of missing teeth.

Periodontitis associated with chronic kidney disease among Mexican Americans

OBJECTIVE In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. METHODS We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. RESULTS Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. CONCLUSION This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population.

Tooth Loss Strongly Associates With Malnutrition in Chronic Kidney Disease

BACKGROUND In chronic kidney disease (CKD), inadequate nutritional intake, inflammation, and increased oxidative stress have been the major contributing factors in malnutrition pathogenesis. However, there is still a paucity of evidence assessing the magnitude of the effect of tooth loss on malnutrition in CKD populations. The authors hypothesize that among patients with CKD, tooth loss may affect nutritional status, using the National Health and Nutrition Examination Survey 1988 to 1994 (NHANES III). METHODS Glomerular filtration rate (GFR) was estimated based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio (albuminuria) was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on estimated GFR <60 mL/minute/1.73m(2) and albuminuria ≥30 mg/g. The cutoff point for serum albumin was set at 3.7 g/dL. Tooth loss categories were based on the number of missing and replaced teeth. RESULTS A total of 2,749 patients was included and stratified based on their oral health status. There was a statistically significant correlation between tooth loss and the proportion of patients with low protein and caloric intake (P = 0.02 and 0.01, respectively). Serum albumin reached a frequency peak in the fully edentulous group without dentures (group 4, 19.2%). In the same group, individuals had lower protein (30.1%) and caloric intake (30.2%) (P = 0.01 and 0.02, respectively). Furthermore, logistic regression analysis confirmed the significant role of tooth loss on serum albumin and protein and energy intake in this population even after adjusting for confounding variables. CONCLUSION Tooth loss independently predicts low energy and protein intake, as well as serum albumin levels, biomarkers of malnutrition in CKD.

Gender Equity in Dental Academics Gains and Unmet Challenges

The need for women in academia to unite was seen in 1881, when Professors Marion Talbot and Ellen Richards founded the American Association of University Women. During this “Progressive Era”, women suffragists fought for and gained the right to vote, first in New Zealand (1893) and later in the United States (1920). As this first wave of feminism grew, it was highlighted by French philosopher Simone de Beauvoir in her book Second Sex, on gender inequality in a patriarchic society (Beauvoir, 1949). Betty Friedan’s The Feminine Mystique sparked the second wave of feminism, presenting the needs of women trapped in a life that they did not necessarily choose (Friedan, 1963). These movements culminated with The Equal Pay Act (1963) and The Equal Rights Amendment (1972), denouncing pay and sex discrimination for women, currently ratified in 35 U.S. states (113th Congress Joint Resolution 10, 2013). These advances led to the Women in Science and Technology Equal Opportunity Act, ensuring that “men and women have equal opportunity in education, training, and employment in scientific and technical fields” (Carter, 1980) and resulting in increased numbers of female investigators funded by the National Science Foundation (24%) and the National Institutes of Health (27%) (NSF, 2012; NIH, 2012). While these social and civil achievements improved the status of women in academia, there are several career challenges remaining related to an increasingly complex work environment. Although the Council of Graduate Education report shows that women are earning more doctoral degrees (52.4%) than men (Allum et al., 2012), women are still held back in achieving successful careers in academics (Shen, 2013). The “Beyond Bias and Barriers” report (National Research Council, 2007) clearly demonstrated that women are less likely to achieve tenure in academic institutions and are often expected to meet higher standards than their male counterparts. Generally, tenure policies lack flexibility for women during their junior faculty/childbearing years (Marchant et al., 2007). Departmental climates have also been shown to influence higher attrition rates among women since they tend to be less satisfied with their jobs and thus are more likely to quit (Nesbitt et al., 2003). Consequently, the conflicts between personal and professional life develop and strongly affect women in terms of faculty promotion and retention, with 40% of women more likely to exit the tenure track for adjunct positions (National Research Council, 2007). When examining global gender issues, the World Economic Forum (Hausmann et al., 2008) measured the gender gap according to 4 distinct criteria: economic participation and opportunity, educational attainment, political empowerment, and health and survival. The Nordic countries are on the top of the list, confirming their consistent gender equality priorities, with the United States ranked 27th, showing modest improvements in wage inequality and political empowerment (Hausmann et al., 2008). These results correlate with the European Union data on gender and research funding (European Commission, 2009), where the Nordic countries are considered proactive, with policies that secure women’s participation in research by encouraging grant applications from women, increasing numbers of women on review boards, and promoting funding transparency. Unlike the United States, the European Commission has been mandating 40% women participation on advisory boards for research funding programs (Vernos, 2013), striving to eliminate bias and enhance the funding success of women academicians in all 27 countries. Despite the Equal Pay Act, salary inequality between men and women has been recognized across all fields and academic appointment levels (West and Curtis, 2006), with women medical scientists earning 80% of male median wages (Goldberg Dey and Hill, 2007). This pay gap, established as early as one year post-bachelor’s degree, widens by 10 years post-degree (69%) and it is consistent for the level of education: Master’s degree (76%), professional degree (72%), and doctoral degree (80%) (Goldberg Dey and Hill, 2007). Among dental faculty, men are consistently compensated at a higher level than women (ADEA, 2011, 2013) (Table). In an examination of the mean salaries for women vs. men in senior dental school positions, where men hold positions at a 3:1 ratio over women, the differentials currently range from

Non-surgical and Supportive Periodontal Therapy: Predictors of Compliance

2,806 to