Safety of Intravenous Thrombolysis for Acute Stroke in Patients with an Active Malignancy: Case Series and Review of the Literature.

INTRODUCTION: Evidence is scarce regarding the safety of alteplase for acute stroke in patients with an active malignancy. METHODS: We reviewed medical records for patients with both conditions treated at our institution over a 2-year period. RESULTS: Five patients were identified, of which only one developed an asymptomatic intracerebral haemorrhage, and no systemic bleedings occurred. Functional outcomes and stroke severity, as measured by National Institutes of Health Stroke Scale and modified Rankin Scale, were favourable upon discharge. CONCLUSION: In the absence of active bleeding or known malignancy of the central nervous system, intravenous alteplase seems a reasonable option for patients with an active cancer and acute stroke.

Assessment of partial-mouth periodontal examination protocols for periodontitis surveillance.

OBJECTIVE: To evaluate bias associated with nine identified partial-mouth periodontal examination (PMPE) protocols in estimating periodontitis prevalence using the periodontitis case definition given by the Centers of Disease Control and Prevention and American Academy of Periodontology (CDC/AAP). MATERIAL AND METHODS: Prevalence from full-mouth examination was determined in a sample of 3667 adults ≥30 years old from the National Health and Nutrition Examination Survey (NHANES) 2009-2010. Prevalence, absolute bias, relative bias, sensitivity and inflation factor were derived for these protocols according to the CDC/AAP definition and half-reduced CDC/AAP definition as ≤50% of sites were measured. RESULTS: Bias in moderate and severe periodontitis prevalence ranged between 11.1-52.5% and 27.1-76.3% for full-mouth mesiobuccal-distolingual protocol and half-mouth mesiobuccal protocol respectively; according to the CDC/AAP definition. With half-reduced CDC/AAP definition, half-mouth four sites protocol provided small absolute bias (3.2%) and relative bias (9.3%) for the estimates of moderate periodontitis prevalence; corresponding biases for severe periodontitis were -1.2% and -10.2%. CONCLUSION: Periodontitis prevalence can be estimated with limited bias when a half-mouth four sites protocol and a half-reduced CDC/AAP case definition are used in combination.

The effect of periodontal therapy on glycaemic control in a Hispanic population with type 2 diabetes: a randomized controlled trial.

OBJECTIVE: In the Mexican-American population, the prevalence of Type 2 diabetes mellitus (T2DM) is as high as 50% of the population. This randomized controlled clinical trial was designed to elucidate how treatment of periodontal disease affects HbA1c values in this population. MATERIALS AND METHODS: One hundred and fifty-four T2DM patients with periodontal disease were enrolled in the study. The test group was treated with scaling and root planing (SRP); the control group received oral hygiene instructions. At baseline and 4-6 weeks after therapy, a complete periodontal examination was performed. Blood was collected at baseline and 4 months later for HbA1c levels. RESULTS: One hundred and twenty-six individuals completed the study. Baseline mean ± SD HbA1c for the test and control groups were 9.0 ± 2.3% and 8.4 ± 2.0% respectively. Non-significant difference in HbA1c reductions (0.6 ± 2.1% and 0.3 ± 1.7%) was found between test and control groups at 4 months. Comparisons of the periodontal clinical parameters between the test and control groups found significant differences with improved results in the test subjects. CONCLUSIONS: No statistically significant differences were found in the changes of HbA1c levels between test and control groups. Non-surgical periodontal therapy improved the magnitude of change in periodontal parameters as compared to the control subjects. ClinicalTrials.gov Identifier: NCT01128374.

Assessing periodontitis in populations: a systematic review of the validity of partial-mouth examination protocols.

OBJECTIVE: To estimate bias associated with partial-mouth periodontal examination (PMPE) protocols regarding estimates of prevalence, severity and extent of clinical attachment loss (CAL), pocket depth (PD) and gingival recession (REC). MATERIAL AND METHODS: A search was made for articles published in English, from 1946 to 2012, which compared PMPE versus full-mouth periodontal examination protocols for CAL or PD ≥ 4 mm or REC ≥3 mm thresholds. PMPE protocols were evaluated for sensitivity of estimates of periodontitis prevalence, relative biases for severity and extent estimates. RESULTS: A review of the literature identified 12 studies which reported 32 PMPE protocols. Three PMPE protocols which had sensitivities ≥85% and relative biases ≤0.05 in absolute values for severity and extent estimates were as follows: (1) half-mouth six-sites, (2) diagonal quadrants six-sites and (3) full-mouth mesiobuccal-midbuccal-distobuccal (MB-B-DB). Two other PMPE protocols (full-mouth and half-mouth mesiobuccal-midbuccal-distolingual) performed well for prevalence and severity of periodontitis; however, their performance in estimates of extent was unknown. CONCLUSIONS: Among the 32 PMPE protocols listed, the half-mouth six-sites and full-mouth MB-B-DB protocols had the highest sensitivities for prevalence estimates and lowest relative biases for severity and extent estimates.

Frequency of Tongue Cleaning Impacts the Human Tongue Microbiome Composition and Enterosalivary Circulation of Nitrate.

The oral microbiome has the potential to provide an important symbiotic function in human blood pressure physiology by contributing to the generation of nitric oxide (NO), an essential cardiovascular signaling molecule. NO is produced by the human body via conversion of arginine to NO by endogenous nitric oxide synthase (eNOS) but eNOS activity varies by subject. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. These previous studies did not include detailed information on the oral health of enrolled subjects. Using 16S rRNA gene sequencing and analysis, we determined whether introduction of chlorhexidine antiseptic mouthwash for 1 week was associated with changes in tongue bacterial communities and resting systolic blood pressure in healthy normotensive individuals with documented oral hygiene behaviors and free of oral disease. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition. Twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. These data suggest that management of the tongue microbiome by regular cleaning together with adequate dietary intake of nitrate provide an opportunity for the improvement of resting systolic blood pressure.

Alcohol intake and periodontitis in adults aged ≥30 years: NHANES 2009-2012.

BACKGROUND: Whether an association between alcohol consumption and periodontitis exists is still unclear. This study aimed to assess the association between alcohol consumption and periodontitis. METHODS: 7062 adults 30 years or older who participated in 2009-2010 and 2011-2012 cycles of the National Health and Nutrition Examination Survey (NHANES) were included. Alcohol consumption measurement included self-reported average number of alcoholic drinks per week over the previous 12 months and was categorized into four groups (0, < 1, 1- < 8, and ≥8 drinks per week). Participants were categorized using surveillance case definitions for periodontitis that included both clinical attachment level (CAL) and periodontal probing depth (PD) measurements. The association between alcohol consumption and chronic periodontitis was evaluated by multivariable regression analyses adjusting for age, gender, race/ethnicity, education level, income-to-poverty ratio, smoking, self-rated overall oral health, and HbA1c . RESULTS: The odds ratio (95% confidence interval) of having severe periodontitis was 1.9 (1.2-3) among participants who reported alcohol consumption of ≥8 drinks compared to participants consuming some alcohol but < 1 drink per week on average. Participants who consumed 1- < 8, and ≥8 drinks per week, on average, also had higher mean PD, percentage of sites with PD ≥4 mm, mean CAL, and percentage of sites with CAL ≥3 mm compared to participants reporting consumption of < 1 drink per week. Meanwhile, the odds of having periodontitis, mean PD, extent PD ≥4 mm, mean CAL, and extent CAL ≥3 mm were not significantly different for nondrinkers than for participants who consumed some alcohol but < 1 drink per week on average. CONCLUSIONS: Alcohol consumption was associated with an increase in the likelihood of having periodontitis, particularly severe periodontitis. Consumption of some alcohol, < 1 drink per week on average, was associated with similar odds of having periodontitis compared to consumption of no alcohol.

Survival of Dental Implants Placed in Grafted and Nongrafted Bone: A Retrospective Study in a University Setting.

PURPOSE: To compare dental implant survival rates when placed in native bone and grafted sites. Additionally, risk factors associated with dental implant loss were identified. This study was based on the hypothesis that bone grafting has no effect on implant survival rates. MATERIALS AND METHODS: A retrospective chart review was conducted for patients receiving dental implants at the University of Texas, School of Dentistry from 1985 to 2012. Exclusion criteria included patients with genetic diseases, radiation and chemotherapy, or an age less than 18 years. To avoid misclassification bias, implants were excluded if bone grafts were only done at the same time of placement. Data on age, sex, tobacco use, diabetes, osteoporosis, anatomical location of the implant, implant length and width, bone graft, and professional maintenance were collected for analysis. RESULTS: A total of 1,222 patients with 2,729 implants were included. The cumulative survival rates at 5 and 10 years were 92% and 87% for implants placed in native bone and 90% and 79% for implants placed in grafted bone, respectively. The results from multivariate analysis (Cox regression) indicated no significant difference in survival between the two groups; having maintenance therapy after implant placement reduced the failure rate by 80% (P < .001), and using tobacco increased the failure rate by 2.6-fold (P = .001). CONCLUSION: There was no difference in the dental implant survival rate when implants were placed in native bone or bone-grafted sites. Smoking and lack of professional maintenance were significantly related to increased implant loss.

Partial-mouth periodontal examination protocol for estimating periodontitis extent and severity in a US population.

We have previously demonstrated that half-mouth four-site periodontal examination protocol performed well in estimating periodontitis prevalence. This study aimed to assess biases associated with this same protocol in estimating periodontitis extent and severity in a United States population. Periodontitis extent as determined by percentage of sites with clinical attachment loss (CAL) ≥3, and ≥5 mm and severity as determined by mean CAL were calculated for full-mouth examination and half-mouth four-site protocol based on 3734 adults sampled from the National Health and Nutrition Examination Survey 2009-2010. Probing depth was excluded because of low data reliability. The comparison between full-mouth and half-mouth assessments was based on bias, relative bias, Wilcoxon signed-rank test, and intra-class correlation coefficient (ICC). For full-mouth examination, periodontitis extent was 21.2% for CAL ≥3 mm and 6.9% for CAL ≥5 mm; periodontitis severity (mean CAL) was 1.73 mm. Half-mouth four-site protocol provided bias -1.2% and relative bias -5.7% for extent (CAL ≥3 mm). Corresponding numbers were -0.3% and 4.3% for extent (CAL ≥5 mm), -0.05 mm and -2.9% for severity. Although the difference between full-mouth and half-mouth assessments was statistically significant, ICCs between them were ≥0.96 for extent (CAL ≥3, 5 mm), and severity (mean CAL). Half-mouth four-site protocol performed well in estimating periodontitis extent and severity based on CAL. Therefore, this protocol should be considered for periodontitis surveillance.

Altered gene expression in human cleidocranial dysplasia dental pulp cells.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder characterised by defects of bone and tooth development. The dental manifestations in CCD patients include supernumerary teeth, delayed tooth eruption, tooth hypoplasia and absence of cellular cementum formation. This disorder is associated with mutations in the osteoblast-specific transcription factor Runx2. To identify morphological and molecular alterations associated with CCD dental tissues, human primary dental pulp cell cultures were established from age- and sex-matched CCD and normal patients. Dental pulp cells were compared for general morphology, proliferation rates, and gene expression profiles using cDNA microarray technology. CCD pulp cells were about four-fold larger than normal cells, however the normal pulp proliferation rates were two- and three-fold greater at time points tested than the CCD cells. Of the 226 genes analysed by blot microarray, 18.6% displayed significant differences at least two-fold in expression levels. This includes 25 genes (11.1%) that were up-regulated, while 17 (7.5%) that were down-regulated in the CCD cells as compared to the normal cells. Expression of selected genes was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Comparison between the CDD and normal cells revealed that gene expression of cytokines and growth factors, such as leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and transforming growth factor beta receptor II (TGF-betaRII) and vascular endothelial growth factor B (VEGFB) were higher while bone morphogenetic protein 2 (BMP2) was lower in the CCD cells. Furthermore, potential Runx2 binding sites were found in all putative target gene promoters. This study suggests that in addition to bone and tooth cell differentiation, Runx2 may be involved in controlling cell growth during tooth development.

Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions.

Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells.

Classic embryological studies have documented the inductive role of root dentin on adjacent periodontal ligament differentiation.  The biochemical composition of root dentin includes collagens and cleavage products of dentin sialophosphoprotein (DSPP), such as dentin sialoprotein (DSP).  The high abundance of DSP in root dentin prompted us to ask the question whether DSP or peptides derived thereof would serve as potent biological matrix components to induce periodontal progenitors to further differentiate into periodontal ligament cells. Here, we test the hypothesis that domain of DSP influences cell fate. In situ hybridization and immunohistochemical analyses showed that the COOH-terminal DSP domain is expressed in mouse periodontium at various stages of root development. The recombinant COOH-terminal DSP fragment (rC-DSP) enhanced attachment and migration of human periodontal ligament stem cells (PDLSC), human primary PDL cells without cell toxicity. rC-DSP induced PDLSC cell proliferation as well as differentiation and mineralization of PDLSC and PDL cells by formation of mineralized tissue and ALPase activity. Effect of rC-DSP on cell proliferation and differentiation was to promote gene expression of tooth/bone-relate markers, transcription factors and growth factors. The results for the first time showed that rC-DSP may be one of the components of cell niche for stimulating stem/progenitor cell proliferation and differentiation and a natural scaffold for periodontal regeneration application.

Bone morphogenetic protein 2 mediates dentin sialophosphoprotein expression and odontoblast differentiation via NF-Y signaling.

Dentin sialophosphoprotein (DSPP), an important odontoblast differentiation marker, is necessary for tooth development and mineralization. Bone morphogenetic protein 2 (BMP2) plays a vital role in odontoblast function via diverse signal transduction systems. We hypothesize that BMP2 regulates DSPP gene transcription and thus odontoblast differentiation. Here we report that expression of BMP2 and DSPP is detected during mouse odontogenesis by in situ hybridization assay, and BMP2 up-regulates DSPP mRNA and protein expression as well as DSPP-luciferase promoter activity in mouse preodontoblasts. By sequentially deleting fragments of the mouse DSPP promoter, we show that a BMP2-response element is located between nucleotides -97 and -72. By using antibody and oligonucleotide competition assays in electrophoretic mobility shift analysis and chromatin immunoprecipitation experiments, we show that the heterotrimeric transcription factor Y (NF-Y) complex physically interacts with the inverted CCAAT box within the BMP2-response element. BMP2 induces NF-Y accumulation into the nucleus increasing its recruitment to the mouse DSPP promoter in vivo. Furthermore, forced overexpression of NF-Y enhances promoter activity and increases endogenous DSPP protein levels. In contrast, mutations in the NF-Y-binding motif reduce BMP2-induced DSPP transcription. Moreover, inhibiting BMP2 signaling by Noggin, a BMP2 antagonist, results in significant inhibition of DSPP gene expression in preodontoblasts. Taken together, these results indicate that BMP2 mediates DSPP gene expression and odontoblast differentiation via NF-Y signaling during tooth development.