Relationship Between Oral Health and Clinical Osteoporosis Among Hospitalized Patients with and Without Diabetes.

Objective Diabetes mellitus (DM) is associated with poor oral health and osteoporosis (OP). The aim of this study was to assess the relationship between OP, periodontal disease (PD), and other dental and health outcomes in a cohort of hospitalized patients with and without DM. Method Using a cross-sectional study design, we enrolled consecutive hospitalized patients. We administered a questionnaire to gather demographic information, oral health history, smoking history, and history of OP. We inspected their dentition and reviewed their charts. Data were analyzed using t-tests, chi-square tests, and logistic regression models. Result  Out of 301 patients enrolled, 275 had PD, 102 had DM, and 30 had OP. In univariate analyses, factors associated with OP included older age (p<0.001), female gender (p=0.046), presence of DM (p=0.049), and having more discharge medications (p=0.01). There was no significant relationship between PD and OP. In logistic regression analyses, age remained significantly associated with having OP among all hospitalized patients and in the non-DM populations. In the DM population, female gender was the only significant predictor for having OP. Conclusion Although we found no significant relationship between having PD and OP in our population, we found that among patients with DM, female gender predicted OP, whereas in patients without DM, age was a stronger predictor. Earlier screening for OP in female patients with DM may be useful in identifying and treating OP sooner in this population.

Relationship between dental loss and health outcomes among hospitalized patients with and without diabetes.

There is mixed evidence regarding the impact of poor dental health on cardiovascular disease and other health outcomes. Our objective was to determine the outcomes associated with poor dental health among hospitalized patients with and without diabetes mellitus (DM) at our institution. We enrolled a consecutive sample of adult patients admitted to an academic medical center. We gathered demographic, health and dental information, reviewed their medical records and then examined their teeth. We analyzed data using SPSS V.24. There was a high prevalence of dental loss among all hospitalized patients. Older age (p<0.001), smoking (p=0.034), having DM (p=0.001) and lower frequency of teeth brushing (p<0.001) were predictors of having a lower number of healthy teeth. Among DM and non-DM patients, fewer remaining healthy teeth was associated with presence of heart disease (p=0.025 and 0.003, respectively). Patients with diabetes mellitus (DM) had a higher prevalence of stroke (p=0.006) while patients without DM had a higher number of discharge medications (p=0.001) associated with having fewer number of healthy teeth. There was no correlation between number of healthy teeth and the length or frequency of hospitalization. Patients with DM are more likely to have fewer number of healthy teeth compared with non-DM patients. Fewer number of healthy teeth was associated with higher prevalence of heart disease in both DM and non-DM patients and with more discharge medications in non-DM patients.

The ER-mitochondria encounter structure contributes to hyphal growth, mitochondrial morphology and virulence of the pathogenic mold Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic fungal pathogen and the primary causative species of invasive aspergillosis, a systemic disease associated with high mortality rates. Treatment of invasive fungal infection relies on a very limited number of antifungal drug classes. In order to extend the spectrum of antifungal drugs novel target structures have to be identified. The ER-mitochondria encounter structure (ERMES), a recently discovered tether that links mitochondria and endoplasmic reticulum, is a potential drug target based on its absence in Metazoa. Very recently, it was shown that ERMES is important for the fitness and immune evasion of the pathogenic yeast Candida albicans. We studied the role of the four ERMES core components Mdm10, Mdm12, Mdm34 and Mmm1 in the pathogenic mold A. fumigatus. By construction and characterizing conditional mutants of all four core components and deletion mutants of mdm10 and mdm12, we show that each component is of significant importance for growth of the fungal pathogen. While markedness of the individual mutant phenotypes differed slightly, all components are important for maintenance of the mitochondrial morphology and the intra-organellar distribution of nucleoids. Characterization of the Mmm1 ERMES mutant in a Galleria mellonella infection model indicates that ERMES contributes to virulence of A. fumigatus. Our results demonstrate that pharmacologic inhibition of ERMES could exert antifungal activity against this important pathogen.

Changes in Inflammatory and Bone Turnover Markers After Periodontal Disease Treatment in Patients With Diabetes.

BACKGROUND: The underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes. MATERIALS AND METHODS: Using an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline). RESULTS: There were nonsignificant reductions in high-sensitivity C-reactive protein (6.34-5.52mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37-10.01pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50-90.23pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45-8.79pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133). CONCLUSIONS: Treatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects.

DENTAL LOSS AMONG AMBULATORY PATIENTS WITH DIABETES.

AIMS: There is a high prevalence of dental loss among patients with diabetes. Understanding the factors that impact dental loss in this population will aid with developing new strategies for its prevention. METHODS: Using a cross-sectional study design, diabetes patients presenting for routine clinic visit were evaluated with an investigator-administered questionnaire. Data was collected on demographics, dental history, duration, control and complications of diabetes. RESULTS: Among 202 subjects, 100 were female, mean age: 58.9 ± 13.2 years, duration of diabetes: 15.8 ± 11.0 years, and hemoglobin A1c: 7.7 ± 1.6%. Thirty-one patients (15.3%) had lost all their teeth and only 13 (6.4%) had all 32 of their natural teeth. Using multiple linear regression, older age (ß= - 0.146; 95% CI: - 0.062 to - 0.230), not flossing (ß= - 3.462; 95% CI: - 1.107 to - 5.817), and presence of diabetic retinopathy (ß= - 4.271; 95% CI: - 1.307 to - 7.236) were significant predictors of dental loss. CONCLUSIONS: Dental loss is common in patients with diabetes and is associated with older age, diabetic retinopathy and not flossing. In order to reduce dental loss among patients with diabetes, regular flossing should be emphasized as an important component of dental care.

Mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus: therapeutic and evolutionary implications.

Mitochondria within eukaryotic cells continuously fuse and divide. This phenomenon is called mitochondrial dynamics and crucial for mitochondrial function and integrity. We performed a comprehensive analysis of mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus. Phenotypic characterization of respective mutants revealed the general essentiality of mitochondrial fusion for mitochondrial genome maintenance and the mold's viability. Surprisingly, it turned out that the mitochondrial rhomboid protease Pcp1 and its processing product, s-Mgm,1 which are crucial for fusion in yeast, are dispensable for fusion, mtDNA maintenance and viability in A. fumigatus. In contrast, mitochondrial fission mutants show drastically reduced growth and sporulation rates and increased heat susceptibility. However, reliable inheritance of mitochondria to newly formed conidia is ensured. Strikingly, mitochondrial fission mutants show a significant and growth condition-dependent increase in azole resistance. Parallel disruption of fusion in a fission mutant partially rescues growth and sporulation defects and further increases the azole resistance phenotype. Taken together, our results indicate an emerging dispensability of the mitochondrial rhomboid protease function in mitochondrial fusion, the suitability of mitochondrial fusion machinery as antifungal target and the involvement of mitochondrial dynamics in azole susceptibility.

Impact of periodontal disease on outcomes in diabetes.

INTRODUCTION: The prevalence of periodontal disease (POD) among adults aged 30years and older in the United States is reported to be more than 47%, with higher prevalence seen among patients with diabetes mellitus (DM). POD has been associated with systemic inflammation, a known risk factor for cardiovascular and bone disease, both of which are more common in patients with DM. However, there is mixed evidence that treatment of POD reduces inflammation, improves DM control, and reduces DM complications. Our study objectives are to assess factors associated with POD in patients with DM and determine the impact of POD treatment on inflammation and bone turnover biomarkers associated with complications of DM. METHODS: In this pilot study, we will first recruit 200 patients with DM to complete a 48-item investigator-administered questionnaire designed to assess socio-economic status, oral health status, adequacy of oral care, glycemic control and presence of DM complications. Responses will be verified by individual chart review. Then, using a crossover design, a subgroup of 24 subjects with responses suggestive of POD will be assigned to undergo POD treatment for three months followed by three months of routine dental care (group 1) or be followed for three months during routine dental care then receive POD treatment for three months (group 2). Outcome measures will be collected before and after POD treatment and include glycemic control and inflammatory and bone turnover biomarkers. RESULTS: We hypothesize that the prevalence of POD among DM patients will be associated with inadequate glycemic control and greater DM complications.

Role of the guanine nucleotide exchange factor Rom2 in cell wall integrity maintenance of Aspergillus fumigatus.

Aspergillus fumigatus is a mold and the causal agent of invasive aspergillosis, a systemic disease with high lethality. Recently, we identified and functionally characterized three stress sensors implicated in the cell wall integrity (CWI) signaling of this pathogen, namely, Wsc1, Wsc3, and MidA. Here, we functionally characterize Rom2, a guanine nucleotide exchange factor with essential function for the cell wall integrity of A. fumigatus. A conditional rom2 mutant has severe growth defects under repressive conditions and incorporates all phenotypes of the three cell wall integrity sensor mutants, e.g., the echinocandin sensitivity of the Δwsc1 mutant and the Congo red, calcofluor white, and heat sensitivity of the ΔmidA mutant. Rom2 interacts with Rho1 and shows a similar intracellular distribution focused at the hyphal tips. Our results place Rom2 between the cell surface stress sensors Wsc1, Wsc3, MidA, and Rho1 and their downstream effector mitogen-activated protein (MAP) kinase module Bck1-Mkk2-MpkA.

A high-resolution association mapping panel for the dissection of complex traits in mice.

Systems genetics relies on common genetic variants to elucidate biologic networks contributing to complex disease-related phenotypes. Mice are ideal model organisms for such approaches, but linkage analysis has been only modestly successful due to low mapping resolution. Association analysis in mice has the potential of much better resolution, but it is confounded by population structure and inadequate power to map traits that explain less than 10% of the variance, typical of mouse quantitative trait loci (QTL). We report a novel strategy for association mapping that combines classic inbred strains for mapping resolution and recombinant inbred strains for mapping power. Using a mixed model algorithm to correct for population structure, we validate the approach by mapping over 2500 cis-expression QTL with a resolution an order of magnitude narrower than traditional QTL analysis. We also report the fine mapping of metabolic traits such as plasma lipids. This resource, termed the Hybrid Mouse Diversity Panel, makes possible the integration of multiple data sets and should prove useful for systems-based approaches to complex traits and studies of gene-by-environment interactions.

Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901) across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.