In vitro effect of over-the-counter probiotics on the ability of Candida albicans to form biofilm on denture strips.

PURPOSE: There is a burgeoning recognition and interest in the potential of probiotics in the treatment and prevention of oral candidiasis associated with the use of dentures. Our aim was to investigate if commercially available over-the-counter probiotics can influence the ability of Candida albicans to form biofilms, which is considered a hallmark of the initiation and progression of oral candidiasis. METHODS: We conducted a 2×5 factorial in vitro study to culture C. albicans on denture strips and challenge with one of the following four commercially available probiotics in bacterial or cell-free supernatant form: Accuflora®, Align®, Culturelle® and Sustenex®. C. albicans biofilm formation was studied in triplicates in all factorial combinations of the study and assessed qualitatively with fluorescence microscopy and quantitatively with tetrazolium salt (XTT) reduction assay. Quality control measures included determination of coefficient of variation, Bland Altman plots and Pittman's test. Results were analyzed using two-way analysis of variance (ANOVA) with pairwise post-hoc Scheffe's tests. RESULTS: Our experimental conditions passed the quality control checks. Two-way ANOVA results indicated that cell-free supernatants provided a stronger and significant inhibitory effect on biofilm formation than their bacterial counterparts (2-way ANOVA p=3.8×10(-6)). Further, Lactobacillus-containing probiotic formulations (Accuflora® and Culturelle®) significantly reduced biofilm formation especially in supernatant form. CONCLUSION: Commercially available probiotics that contain Lactobacilli species interfere with the in vitro ability of C. albicans to form biofilms on dentures. The mechanistic and clinical implications of our results need to be addressed by larger in vivo studies.

Lack of association of the APOE epsilon 4 allele with the risk of obstructive sleep apnea: meta-analysis and meta-regression.

STUDY OBJECTIVES: Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)--a vital macromolecule in cholesterol metabolism--with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE epsilon4 allele with the risk of OSA. DESIGN: Random effects meta-analysis and meta-regression. SETTING: Genetic epidemiological studies reporting the association of APOE epsilon4 allele with OSA susceptibility. PATIENTS OR PARTICIPANTS: Synthesis of APOE epsilon4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE epsilon4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86-1.47). There was a statistically significant heterogeneity (I2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE epsilon4 allele or when grouped based on the geographic location of the study. CONCLUSIONS: The hypothesis that the APOE epsilon4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Arbitrary units are a composite and useful measure of muscle sympathetic nerve activity.

In humans, the muscle sympathetic nerve activity (MSNA) signal is challenging to detect, record and analyze. Several methods exist that attempt to capture the latent construct of MSNA. We directly compared the performance of five MSNA parameters: burst frequency, burst incidence, median burst amplitude, arbitrary units (AU) and fractal dimension (FD). The MSNA signal was recorded in 33 subjects for approximately 30 min before, during and after the application of a graded cold pressor test stimulus at 18 degrees C, 10 degrees C and 2 degrees C in random order with an adequate wash-out period. Using coefficient of variation, Shannon's entropy and principal component analysis, we observed that these five parameters defined two physical and conceptual domains of MSNA-frequency and amplitude. Since AU combines information from both these domains, we observed that it explained maximum inter-subject and inter-experimental segment variation. FD did not explain the inter-subject variability and was identified as a unique parameter in the factor analysis. Epidemiological studies that attempt to quantify MSNA may consistently use AU as the parameter for quantification of MSNA.

Factors influencing the benefit of adjunctive devices during percutaneous coronary intervention in ST-segment elevation myocardial infarction: meta-analysis and meta-regression.

BACKGROUND: Routine use of adjunctive devices to percutaneous coronary intervention (PCI) for the treatment of patients of ST-segment elevation myocardial infarction (STEMI) is questionable. Also, the clinical characteristics of STEMI patients that can modulate the treatment benefits of adjunctive devices are not fully understood. OBJECTIVE: To synthesize the existing literature to summarize the therapeutic benefit of the adjunctive devices and to identify the patient characteristics which relate to this therapeutic benefit. METHODS: We conducted (i) meta-analyses of the randomized controlled trials (RCT) comparing the performance of the adjunctive devices with PCI for three reperfusion-related outcomes: myocardial blush grade (MBG) < 3, failed ST-segment resolution (STR), and Thrombolysis In Myocardial Infarction (TIMI) flow grade < 3; (ii) stepwise meta-regressions of the effect of trial characteristics on between-trial heterogeneity; and (iii) analyses to examine whether the reperfusion-related end-points explained the between-trial difference in cardiac death and major adverse cardiac events (MACE). RESULTS: Our meta-analyses represent data from 23 RCT and 5,728 subjects. The overall therapeutic benefit attributable ranged from 32 to 35% for the reperfusion-related outcomes, and thrombectomy devices were more beneficial than the distal protection devices.Meta-regression identified gender, receipt of glycoprotein (GP) IIb/IIIa inhibitor, and baseline TIMI flow grade as significant predictors of improved reperfusion across trials. The available clinical trials were individually underpowered and not designed to detect the influence of adjunctive devices on death or MACE. CONCLUSIONS: Routine use of adjunctive devices cannot be recommended. Thrombus burden, treatment with GPIIb/IIIa inhibitors, and gender may modify the reperfusion benefit of adjunctive devices.

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification.

BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that--assuming each molecular biomarker to be a diagnostic test--enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i) subjects having cancer with those without; ii) subjects with two different cancers; iii) subjects with two different types of one cancer; and iv) subjects with same cancer resulting in differential time to metastasis. RESULTS: Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

Insights into age- and sickle-cell-disease-interaction using principal components analysis.

BACKGROUND: In the context of sickle cell anemia, peripheral blood indexes provide key information that is also potentially influenced by age. Therefore, it is necessary to understand the extent and nature of interactions between sickle cell anemia and age, especially in situations where there is a high prevalence of sickle cell anemia. METHODS: In a cross-sectional study of 374 subjects with varying hemoglobin S (HbS) status, we characterized the interaction between age and sickle hemoglobin using principal components analysis. RESULTS: Factor analysis in subjects with hemoglobin AA identified three orthogonal factors--normal erythropoiesis, presence of thalassemia and the aggregability potential of the blood. These three factors were differentially associated with hemoglobin status. Age influenced the association of factors #2 and #3 with hemoglobin status. CONCLUSION: Our findings suggest that the interaction between age and hemoglobin status needs to be considered in both clinical and public health settings.

Association of umbilical cord blood lead with neonatal behavior at varying levels of exposure.

BACKGROUND: In the light of the ongoing debate about lowering the cut-off for acceptable blood lead level to <5 microg/dL from the currently recommended level of <10 microg/dL, we considered whether prenatal exposure to varying levels of lead is associated with similar or disparate effects on neonatal behavior. METHODS: Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an epidemiological approach and robust statistical techniques like multivariate linear regression, logistic regression, Poisson regression and structural equations modeling analyses we estimated the simultaneous indirect effects of umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS clusters. RESULTS: We observed that when analyzed in all study subjects, the CBL levels independently and strongly influenced autonomic stability and abnormal reflexes clusters. However, when the analysis was restricted to neonates with CBL <10 microg/dL, CBL levels strongly influenced the range of state, motor and autonomic stability clusters. Abnormal walking reflex was consistently associated with an increased CBL level irrespective of the cut-off for CBL, however, only at the lower cut-offs were the predominantly behavioral effects of CBL discernible. CONCLUSION: Our results further endorse the need to be cognizant of the detrimental effects of blood lead on neonates even at a low-dose prenatal exposure.

A prospective cohort study of postoperative complications in the management of perforated peptic ulcer.

BACKGROUND: With dwindling rates of postoperative mortality in perforated peptic ulcer that is attributable to H2-receptor blocker usage, there is a need to shift the focus towards the prevention of postoperative morbidity. Further, the simultaneous contribution of several putative clinical predictors to this postoperative morbidity is not fully appreciated. Our objective was to assess the predictors of the risk, rate and number of postoperative complications in surgically treated patients of perforated peptic ulcer. METHODS: In a prospective cohort study of 96 subjects presenting as perforated peptic ulcer and treated using Graham's omentoplatsy patch or gastrojejunostomy (with total truncal vagotomy), we assessed the association of clinical predictors with three domains of postoperative complications: the risk of developing a complication, the rate of developing the first complication and the risk of developing higher number of complications. We used multiple regression methods - logistic regression, Cox proportional hazards regression and Poisson regression, respectively - to examine the association of the predictors with these three domains. RESULTS: We observed that the risk of developing a postoperative complication was significantly influenced by the presence of a concomitant medical illness [odds ratio (OR) = 8.9, p = 0.001], abdominal distension (3.8, 0.048) and a need of blood transfusion (OR = 8.2, p = 0.027). Using Poisson regression, it was observed that the risk for a higher number of complications was influenced by the same three factors [relative risk (RR) = 2.6, p = 0.015; RR = 4.6, p < 0.001; and RR = 2.4, p = 0.002; respectively]. However, the rate of development of complications was influenced by a history suggestive of shock [relative hazards (RH) = 3.4, p = 0.002] and A- blood group (RH = 4.7, p = 0.04). CONCLUSION: Abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative management in patients of perforated peptic ulcer.

Predictive performance of anthropometric indexes of central obesity for the risk of type 2 diabetes.

BACKGROUND: In spite of several available anthropometric indexes, the relative merit of these indexes for the prediction of type 2 diabetes remains unknown. Considering that obesity and diabetes commonly coexist as co-morbidities, our objective was to directly compare the performance of measures of central and general obesity to predict the risk of type 2 diabetes. METHODS: We conducted a case-control study of type 2 diabetes on 150 cases and 150 age- and gender-matched controls. We directly compared the predictive performance of five anthropometric indexes: four related to central obesity--waist circumference (WC), waist/hip ratio (WHR), abdominal volume index (AVI) and conicity index (CI); and one related to general obesity--body mass index (BMI). We used various statistical approaches like area under (AUC) receiver-operating characteristic (ROC) curves, likelihood ratios, logistic regression and Shannon's entropy to compare the performance of the indexes in the study sample as well as bootstrapped samples. RESULTS: WC had the highest overall predictive accuracy that was gender insensitive (AUC=0.77 in males and 0.74 in females); a comparable information content as that of AVI (Shannon's entropy=1.81 for WC and 1.84 for AVI) and was a better predictor of the risk of type 2 diabetes than all the remaining indexes. WC also correlated strongly with the biochemical markers of diabetes like blood sugar and lipid profile. CONCLUSIONS: WC is a simple, non-invasive and accurate predictor of the risk of type 2 diabetes that can potentially be used in screening programs in developing countries.