Clinical and subclinical effects of power brushing following experimental induction of biofilm overgrowth in subjects representing a spectrum of periodontal disease.

AIM: Investigate short-term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states. MATERIALS AND METHODS: Overall, 175 subjects representing each of five biofilm-gingival interface (BGI) periodontal groups were enrolled in a single-blind, randomized study. After stent-induced biofilm overgrowth for 21 days subjects received either a manual or a power toothbrush to use during a 4 weeks resolution phase. At baseline and during induction and resolution, standard clinical parameters were measured. Subclinical parameters included multikine analysis of 13 salivary biomarkers and 16s Human Oral Microbe Identification Microarray (HOMIM) probe analysis of subgingival plaque samples. RESULTS: All groups exhibited significantly greater reductions in bleeding on probing (BOP) (p = 0.002), gingival index (GI) (p = 0.0007), pocket depth (PD) (p = 0.04) and plaque index (p = 0.001) with power brushing compared to manual. When BGI groups were combined to form a shallow PD (PD ≤ 3 mm) and a deep PD group (PD > 4 mm) power brushing reduced BOP and GI in subjects with both pocket depths. Power brushing significantly reduced IL-1ß levels at resolution while changes in bacterial levels showed non-significant trends between both brushing modalities. CONCLUSIONS: Short-term changes in select clinical parameters and subclinical salivary biomarkers may be useful in assessing efficacy of power brushing interventions in a spectrum of periodontal disease states.

Evaluation of a Curved Design Rubber Bristle Interdental Cleaner on Patients with Gingivitis.

Purpose: The purpose of this clinical study was to evaluate the effectiveness of a curved rubber bristle interdental cleaner, as compared to dental floss, in the reduction of gingivitis and plaque.Methods: Gingival Index (GI), Bleeding on Probing (BOP), Periodontal Probing Depth (PPD) and Modified QH Plaque Index (MQH-PI) parameters were evaluated in an examiner-masked, parallel group, controlled clinical study. A total of 50 participants with gingivitis (no site with PPD >4 mm, BOP ≥10% but ≤50%) met the eligibility criteria. Participants were randomly assigned to either the curved rubber bristle interdental cleaner (cRBIC) group or the ADA-accepted dental floss (Floss) group. Participants used the devices for four weeks. Parameters were obtained at 2 and 4 weeks. Participants scored their level of product familiarity, satisfaction and motivation for interdental cleaning.Results: There were no statistically significant differences between the two groups in changes from baseline to 2 or 4 weeks in GI, BOP%, and MQH-PI. However, cRBIC group showed greater reduction of PPD at 4 weeks from baseline, compared with Floss group (p<0.05). The cRBIC group showed overall better compliance level than Floss group. The mean score of "ease of use" of the cRBIC group was significantly greater than that of Floss group. However, Floss group showed higher levels of "satisfaction" than cRBIC group. Motivation for interdental cleaning was higher in cRBIC.Conclusion: The cRBIC was similar to Floss in clinical effectiveness; however, PPD reduction at 4 weeks was greater with the cRBIC. Ease of use of cRBIC may have affected the participants' motivation for interdental cleaning, resulting in better compliance.

The nuclear factor kappa-B pathway in airway epithelium regulates neutrophil recruitment and host defence following Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa pneumonia usually results from a deficit of the innate immune system. To investigate whether inflammatory signalling by airway epithelial cells provides a pivotal line of defence against P. aeruginosa infection, we utilized two separate lines of inducible transgenic mice that express a constitutive activator of the nuclear factor kappa-B (NF-kappaB) pathway (IKTA) or a dominant inhibitor of NF-kappaB (DNTA) in airway epithelial cells. Compared with control mice, IKTA mice showed an enhanced host response to P. aeruginosa infection with greater neutrophil influx into the lungs, increased expression of Glu-Leu-Arg-positive (ELR(+)) CXC chemokines macrophage inflammatory protein-2 and keratinocyte chemoattractant (KC), superior bacterial clearance and improved survival at 24 h after infection. Neutrophil depletion abrogated the improvement in host defence identified in IKTA mice. In contrast, DNTA mice showed impaired responses to P. aeruginosa infection with higher bacterial colony counts in the lungs, decreased neutrophilic lung inflammation and lower levels of KC in lung lavage fluid. DNTA mice given recombinant KC at the time of P. aeruginosa infection demonstrated improved neutrophil recruitment to the lungs and enhanced bacterial clearance. Our data indicate that the NF-kappaB pathway in airway epithelial cells plays an essential role in defence against P. aeruginosa through generation of CXC chemokines and recruitment of neutrophils.

Digital breast Tomosynthesis vacuum assisted biopsy for Tomosynthesis-detected Sonographically occult lesions.

PURPOSE: To assess the utility and pathological results from DBT VAB for lesions occult on 2D mammography and breast ultrasound (US). MATERIALS AND METHODS: A retrospective review of 1116 consecutive stereotactic biopsies was performed over 27months. DBT VAB was performed for 38 non-calcified lesions which were solely detected using DBT. Imaging findings and pathology results were reviewed. RESULTS: Pathologic findings were malignant in 8 of 38 lesions [masses (5) and distortion (3)]. High-risk findings found in 14 lesions. CONCLUSION: DBT VAB is easily performed and the majority of cases yield actionable pathologies. Therefore, perform DBT VAB primarily when available.

Automated assay optimization with integrated statistics and smart robotics.

The transition from manual to robotic high throughput screening (HTS) in the last few years has made it feasible to screen hundreds of thousands of chemical entities against a biological target in less than a month. This rate of HTS has increased the visibility of bottlenecks, one of which is assay optimization. In many organizations, experimental methods are generated by therapeutic teams associated with specific targets and passed on to the HTS group. The resulting assays frequently need to be further optimized to withstand the rigors and time frames inherent in robotic handling. Issues such as protein aggregation, ligand instability, and cellular viability are common variables in the optimization process. The availability of robotics capable of performing rapid random access tasks has made it possible to design optimization experiments that would be either very difficult or impossible for a person to carry out. Our approach to reducing the assay optimization bottleneck has been to unify the highly specific fields of statistics, biochemistry, and robotics. The product of these endeavors is a process we have named automated assay optimization (AAO). This has enabled us to determine final optimized assay conditions, which are often a composite of variables that we would not have arrived at by examining each variable independently. We have applied this approach to both radioligand binding and enzymatic assays and have realized benefits in both time and performance that we would not have predicted a priori. The fully developed AAO process encompasses the ability to download information to a robot and have liquid handling methods automatically created. This evolution in smart robotics has proven to be an invaluable tool for maintaining high-quality data in the context of increasing HTS demands.

A pilot study of a headache program in the workplace. The effect of education.

Headache is a frequent problem in the workplace and contributes to absenteeism and productivity loss. Disease-management programs targeting headache may reduce its impact on employees, employers, and society. A pilot study was conducted in an employer setting (J.P. Morgan & Co., Incorporated; four locations in New York City and two in Delaware) to evaluate a multimedia computer-based (kiosk) headache program. Study objectives included assessing the effect of the program on participant outcomes and evaluating the educational component of the program. Through the kiosk, participants were questioned about the types, severity, and frequency of their headaches; the impact of headaches on their daily activities; and lost workdays as a result of headache. All participants received personalized reports about their headaches, and the participants in New York were given access to an on-site neurologist and additional educational information. A follow-up assessment was requested 3 months after the baseline screening to evaluate the effect of the program. A total of 185 participants completed both a baseline and follow-up session. Of 177 evaluable participants, 19% saw a physician for headache after their initial kiosk session. Fifty-six percent of evaluable participants reported overall improvement in headache symptoms at follow-up (P < 0.01), with decreased headache frequency and better understanding of headache most often selected as reasons for improvement. Participants also reported higher satisfaction with headache management after using the program and fewer urgent care/emergency room visits for headache (P < 0.01). For participants who reported lost workdays because of headache, the number of days missed had decreased by the follow-up. The results of this study indicate that the headache program improved outcomes. Because all participants received educational materials, it is likely that education played a role in the improvements observed. These results are encouraging and warrant further study in larger, controlled trials.

Human immunodeficiency virus western blot tests: comparisons and considerations.

UNLABELLED: Human immunodeficiency virus (HIV) Western Blot (WB) tests are used as an aid in the diagnosis of acquired immunodeficiency disease syndrome (AIDS) and related disorders. The object of this study is to examine and compare the results of four commercially available HIV WB methods. Sera from 974 persons were tested by four (Kits I, II, III, and IV) HIV WB methods from different vendors. The HIV WB were interpreted by recognized criteria published in Morbidity and Mortality Weekly Report. RESULTS: 65 percent of the referred specimens received were HIV enzyme immunoassay (EIA) repeatedly reactive (R), and 35 percent of the referred specimens were HIV EIA nonreactive (NR). The EIA (NR) sera showed the greatest variability for HIV WB results, especially in the indeterminant (I) category. The HIV WB tests commercially available vary in sensitivity and specificity. Standarization of materials and controls and the use of uniform interpretation criteria are needed.

Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes.

The mechanisms by which chronic inflammatory lung diseases, particularly chronic obstructive pulmonary disease, confer enhanced risk for lung cancer are not well-defined. To investigate whether nuclear factor (NF)-κB, a key mediator of immune and inflammatory responses, provides an interface between persistent lung inflammation and carcinogenesis, we utilized tetracycline-inducible transgenic mice expressing constitutively active IκB kinase ß in airway epithelium (IKTA (IKKß trans-activated) mice). Intraperitoneal injection of ethyl carbamate (urethane), or 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) was used to induce lung tumorigenesis. Doxycycline-treated IKTA mice developed chronic airway inflammation and markedly increased numbers of lung tumors in response to urethane, even when transgene expression (and therefore epithelial NF-κB activation) was begun after exposure to carcinogen. Studies using a separate tumor initiator/promoter model (MCA+BHT) indicated that NF-κB functions as an independent tumor promoter. Enhanced tumor formation in IKTA mice was preceded by increased proliferation and reduced apoptosis of alveolar epithelium, resulting in increased formation of premalignant lesions. Investigation of inflammatory cells in lungs of IKTA mice revealed a substantial increase in macrophages and lymphocytes, including functional CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Importantly, Treg depletion using repetitive injections of anti-CD25 antibodies limited excessive tumor formation in IKTA mice. At 6 weeks following urethane injection, antibody-mediated Treg depletion in IKTA mice reduced the number of premalignant lesions in the lungs in association with an increase in CD8 lymphocytes. Thus, persistent NF-κB signaling in airway epithelium facilitates carcinogenesis by sculpting the immune/inflammatory environment in the lungs.

Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden.

The transcription factor nuclear factor kappa B (NF-κB) is activated in human breast cancer tissues and cell lines. However, it is unclear whether NF-κB activation is a consequence of tumor formation or a contributor to tumor development. We developed a doxycycline (dox)-inducible mouse model, termed DNMP, to inhibit NF-κB activity specifically within the mammary epithelium during tumor development in the polyoma middle T oncogene (PyVT) mouse mammary tumor model. DNMP females and PyVT littermate controls were treated with dox from 4 to 12 weeks of age. We observed an increase in tumor latency and a decrease in final tumor burden in DNMP mice compared with PyVT controls. A similar effect with treatment from 8 to 12 weeks indicates that outcome is independent of effects on postnatal virgin ductal development. In both cases, DNMP mice were less likely to develop lung metastases than controls. Treatment from 8 to 9 weeks was sufficient to impact primary tumor formation. Inhibition of NF-κB increases apoptosis in hyperplastic stages of tumor development and decreases proliferation at least in part by reducing Cyclin D1 expression. To test the therapeutic potential of NF-κB inhibition, we generated palpable tumors by orthotopic injection of PyVT cells and then treated systemically with the NF-κB inhibitor thymoquinone (TQ). TQ treatment resulted in a reduction in tumor volume and weight as compared with vehicle-treated control. These data indicate that epithelial NF-κB is an active contributor to tumor progression and demonstrate that inhibition of NF-κB could have a significant therapeutic impact even at later stages of mammary tumor progression.

Phenanthrene biodegradation in freshwater environments.

Phenanthrene, a low-molecular-weight polycyclic aromatic hydrocarbon, was incubated with water samples from various reservoir systems in Tennessee to evaluate the potential for significant polycyclic aromatic hydrocarbon degradation by the indigenous microbial populations. Biodegradation was assessed by comparison of total polycyclic aromatic hydrocarbon substrate recovery in degradation flasks relative to sterile control flasks. During 1977 field studies, the mean phenanthrene biodegradation was approximately 80% after a 4-week incubation. Within a given habitat, 45% of the total variability in phenanthrene biodegradation was attributable to the physical, chemical, and microbiological site characteristics examined. Polycyclic aromatic hydrocarbon degradation was directly related to the historical environmental pollution of the sampling sites examined, the length of biodegradation assessment, temperature, and the molecular size of the polycyclic aromatic hydrocarbon substrate.

Tenax-GC Extraction Technique for Residual Polychlorinated Biphenyl and Polyaromatic Hydrocarbon Analysis in Biodegradation Assays.

A rapid Tenax-GC extraction technique has been evaluated for use in conjunction with aqueous biodegradation assays for polyaromatic hydrocarbons and polychlorinated biphenyls. The method was quantitatively efficient and reproducible for phenanthrene, but variable and not quantitative for Aroclor 1254 (polychlorinated biphenyls). Aqueous sample volumes and varying concentrations of organic matter influenced polychlorinated biphenyl and polyaromatic hydrocarbon extraction efficiency. Phenanthrene recovery was decreased by soil extract but unaffected by spent bacteriological culture medium. Both types of organic matter caused significant reduction of Aroclor 1254 recovery. Polyaromatic hydrocarbon and polychlorinated biphenyl biodegradation assays, performed with reservoir samples, supported the laboratory evaluation. The study demonstrated the utility of the Tenax-GC extraction technique for phenanthrene analysis in biodegradation assessment; however, Tenax-GC extraction was not appropriate for Aroclor 1254 biodegradation studies.

Impact of coal-coking effluent on sediment microbial communities: a multivariate approach.

The functional response to and recovery from coal-coking waste effluent was evaluated for sediment microbial communities. Twenty estimates of microbial population density, biomass, and activity were measured five times during a 15-month period. Significant effects on microbial communities were observed in response to both wastewater contamination and diversion of the wastewater. Multivariate analysis of variance and discriminant analysis indicated that accurate differentiation between uncontaminated and contaminated sediments required a minimum of nine estimates of community response. Total viable population density, ATP, alkaline phosphatase, naphthalene, and phenanthrene mineralization rates were found to be highly weighted variables in site discrimination. Lipid and glucose mineralization, nitrogen fixation, and sediment protein also contributed significantly to explaining variation among sites. Estimates of anaerobic population densities and rates of methane production contributed little to discrimination among sites in the environment examined. In general, total viable population density, ATP, and alkaline phosphatase activity were significantly depressed in contaminated sediments. However, after removal of this contamination, the previously affected sites demonstrated greater temporal variability but a closer approximation of the mean response at the control site. Naphthalene and phenanthrene mineralization did not follow the general trend and were elevated at the contaminated sites throughout the investigation. Results of the investigation supported the hypothesis that multiple functional measures of microbial community response are required to evaluate the effect of and recovery from environmental contamination. In addition, when long-term effects are evaluated, select physiological traits, i.e., polyaromatic hydrocarbon mineralization, may not reflect population and biomass estimates of community response.

Comparative effects of Aroclor 1254 (polychlorinated biphenyls) and phenanthrene on glucose uptake by freshwater microbial populations.

The effects of polychlorinated biphenyl (PCB) and phenanthrene stress on glucose uptake by natural microbial populations were examined by the heterotrophic potential technique. Temporal and spatial distributions in glucose uptake velocities were examined for natural samples as well as PCB- and phenanthrene-stressed samples. Statistical analysis indicated significant variability among the various samples. It was demonstrated that the environmental variables contributed significantly to the variability in uptake kinetics. Although general trends indicated a PCB-induced stimulation in uptake velocities, these trends were in part masked by sample variability. Data analysis indicated no statistically significant PCB or phenanthrene effect on either total glucose uptake velocities or the proportion of 14CO2 evolved, as compared to natural unstressed samples.

Microcosm and experimental pond evaluation of microbial community response to synthetic oil contamination in freshwater sediments.

A multivariate approach was used to evaluate the significance of synthetic oil-induced perturbations in the functional activity of sediment microbial communities. Total viable cell densities, ATP-biomass, alkaline phosphatase and dehydrogenase activity, and mineralization rates of glucose, protein, oleic acid, starch, naphthalene, and phenanthrene were monitored on a periodic basis in microcosms and experimental ponds for 11 months, both before and after exposure to synthetic oil. All variables contributed to significant discrimination between sediment microbial responses in control communities and communities exposed to a gradient of synthetic oil contamination. At high synthetic oil concentrations (4,000 ml/12 m), a transient reduction in sediment ATP concentrations and increased rates of oleic acid mineralization were demonstrated within 1 week of exposure. These transient effects were followed within 1 month by a significant increase in rates of naphthalene and phenanthrene mineralization. After initial construction, both control and synthetic oil-exposed microbial communities demonstrated wide variability in community activity. All experimental microbial communities approached equilibrium and demonstrated good replication. However, synthetic oil perturbation was demonstrated by wide transient variability in community activity. This variability was primarily the result of the stimulation of polyaromatic hydrocarbon mineralization rates. In general, microcosms and pond communities demonstrated sufficient resiliency to recover from the effects of synthetic oil exposure within 3 months, although polyaromatic hydrocarbon mineralization rates remained significantly elevated.