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Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok
OBJECTIVE: Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. METHODS: Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (>/=32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). RESULTS: Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. CONCLUSION: Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.
PMCID:4476681
PMID: 26098888
ISSN: 1932-6203
CID: 1639912

Toothbrush efficacy for plaque removal

Nightingale, Kj; Chinta, Sk; Agarwal, P; Nemelivsky, M; Frisina, Ac; Cao, Z; Norman, Rg; Fisch, Gs; Corby, P
OBJECTIVES: To determine the effectiveness of a novel sonic toothbrush in reducing plaque and in maintenance of gingival health when compared to a standard manual brush. METHODS: This study was a block-randomized, examiner-blind, two-treatment, parallel group, single centre clinical investigation. A total of 84 subjects were enrolled and randomly assigned to receive either the Panasonic EW-DL90 or an American Dental Association-endorsed manual toothbrush. Subjects were instructed to follow a twice-daily brushing regimen without flossing. Plaque levels and gingival health were assessed at baseline and after 1 and 3 weeks of treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the Papillary Bleeding Score. RESULTS: Subjects assigned to the EW-DL90 group had significantly lower plaque levels after 1 and 3 weeks of treatment than those in the manual group (P = 0.003 and 0.0035, respectively). Both groups showed a reduction in plaque levels at Week 3 relative to baseline. The EW-DL90 group had significantly lower gingival inflammation scores after 1 week of treatment (P = 0.0293), but there was no difference between groups after 3 weeks of treatment. CONCLUSION: The EW-DL90 toothbrush safely and effectively removes more plaque than a standard manual toothbrush. Improvement in gingival inflammation was observed after 1 week of treatment. There was no difference in Papillary Bleeding Score between the two groups after 3 weeks of treatment. CLINICAL SIGNIFICANCE: The newly developed sonic brush (Panasonic EW-DL90) tested in this study was found to be more effective than a manual toothbrush at plaque removal. The papillary bleeding scores were significantly lower in the sonic brush group after 1 week of product use. After 3 weeks of product use, both treatment groups had similar papillary bleeding scores almost returning to baseline values.
PMID: 24738786
ISSN: 1601-5029
CID: 882812

Changes in abundance of oral microbiota associated with oral cancer [Meeting Abstract]

Albertson, Donna G; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M; Queiroz, Erica LS; Nightingale, Kira; Kerr, Alexander R; DeLacure, Mark D; Veeramachaneni, Ratna; Olshen, Adam; Schmidt, Brian L
ISI:000349910203349
ISSN: 1538-7445
CID: 1598342

Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

Viet, C T; Corby, P M; Akinwande, A; Schmidt, B L
Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain.
PMCID:4213248
PMID: 24943201
ISSN: 0022-0345
CID: 1042412

Radiographic comparison of different concentrations of recombinant human bone morphogenetic protein with allogenic bone compared with the use of 100% mineralized cancellous bone allograft in maxillary sinus grafting

Froum, Stuart J; Wallace, Stephen; Cho, Sang-Choon; Khouly, Ismael; Rosenberg, Edwin; Corby, Patricia; Froum, Scott; Mascarenhas, Patrick; Tarnow, Dennis P
The purpose of this study was to radiographically evaluate, then analyze, bone height, volume, and density with reference to percentage of vital bone after maxillary sinuses were grafted using two different doses of recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ACS) combined with mineralized cancellous bone allograft (MCBA) and a control sinus grafted with MCBA only. A total of 18 patients (36 sinuses) were used for analysis of height and volume measurements, having two of three graft combinations (one in each sinus): (1) control, MCBA only; (2) test 1, MCBA + 5.6 mL of rhBMP-2/ACS (containing 8.4 mg of rhBMP-2); and (3) test 2, MCBA + 2.8 mL of rhBMP-2/ACS (containing 4.2 mg of rhBMP-2). The study was completed with 16 patients who also had bilateral cores removed 6 to 9 months following sinus augmentation. A computer software system was used to evaluate 36 computed tomography scans. Two time points where selected for measurements of height: The results indicated that height of the grafted sinus was significantly greater in the treatment groups compared with the control. However, by the second time point, there were no statistically significant differences. Three weeks post-surgery bone volume measurements showed similar statistically significant differences between test and controls. However, prior to core removal, test group 1 with the greater dose of rhBMP-2 showed a statistically significant greater increase compared with test group 2 and the control. There was no statistically significant difference between the latter two groups. All three groups had similar volume and shrinkage. Density measurements varied from the above results, with the control showing statistically significant greater density at both time points. By contrast, the density increase over time in both rhBMP groups was similar and statistically higher than in the control group. There were strong associations between height and volume in all groups and between volume and new vital bone only in the control group. There were no statistically significant relationships observed between height and bone density or between volume and bone density for any parameter measured. More cases and monitoring of the future survival of implants placed in these augmented sinuses are needed to verify these results.
PMID: 25171031
ISSN: 0198-7569
CID: 1313742

HIV Infection and Microbial Diversity in Saliva

Li, Yihong; Saxena, Deepak; Chen, Zhou; Liu, Gaoxia; Abrams, Willam R; Phelan, Joan A; Norman, Robert G; Fisch, Gene S; Corby, Patricia M; Dewhirst, Floyd; Paster, Bruce J; Kokaras, Alexis S; Malamud, Daniel
Limited information is available about the effect of human immunodeficiency virus (HIV) and subsequent antiretroviral treatment on host-microbe interaction. This study aimed to determine the salivary microbial composition in 10 HIV-seropositive subjects, before and 6 months after highly active antiretroviral therapy (HAART), compared with that of 10 HIV-seronegative subjects. Both a conventional culture and two culture-independent analyses were used and consistently demonstrated differences in microbial composition among the three sets of samples. HIV+ subjects had higher levels of total cultivable microbes, including oral streptococci, lactobacilli, S. mutans, and Candida, in saliva as compared to HIV- subjects. The total cultivable microbial level was significantly correlated with CD4+ T cell counts. Denaturing gradient gel electrophoresis (DGGE), which compared the overall microbial profiles, showed distinct fingerprinting profiles for each group. Human oral microbe identification microarray (HOMIM), which compared the 16S rRNA genes, showed a clear separation among the three sample groups. Veillonella, Synergistetes, and Streptococcus, were present in all 30 saliva samples. Only minor changes or no changes were observed in the prevalence of Neisseria, Haemophilus, Gemella, Leptotrichia, Solobacterium, Parvimonas and RothiaI. Severn genera were detected only in HIV- samples, including Capnocytophaga, Slackia, Porphyromonas, Kingella, Peptostreptococcaceae, Lactobacillus, and Atopobium. The prevalence of Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, and Atopobium was increased after therapy with HAART. In contrast, the prevalence of Aggregatibacter was significantly decreased after HAART. Findings of this study suggest that HIV infection and therapy with HAART could have a significant effect on salivary microbial colonization and composition.
PMCID:3993673
PMID: 24523469
ISSN: 0095-1137
CID: 807452

Treatment Responses to Tooth Whitening in Twins

Corby, Patricia M A; Biesbrock, Aaron; Gerlach, Robert; Corby, Andrea L; Moreira, Alexandre; Schork, Nicholas J; Bretz, Walter A
The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light-dark), a* (red-green), and b* (yellow-blue) color change from digital images at baseline () and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h2 = 71.0) for b* and a*(p < .0001), but not for L* (h2 = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips.
PMID: 24429255
ISSN: 1832-4274
CID: 741452

Design Aspects of a Case-Control Clinical Investigation of the Effect of HIV on Oral and Gastrointestinal Soluble Innate Factors and Microbes

Phelan, Joan A; Abrams, William R; Norman, Robert G; Li, Yihong; Laverty, Maura; Corby, Patricia M; Nembhard, Jason; Neri, Dinah; Barber, Cheryl A; Aberg, Judith A; Fisch, Gene S; Poles, Michael A; Malamud, Daniel
INTRODUCTION: The impaired host defense system in HIV infection impacts the oral and gastrointestinal microbiota and associated opportunistic infections. Antiretroviral treatment is predicted to partially restore host defenses and decrease the oral manifestation of HIV/AIDS. Well-designed longitudinal studies are needed to better understand the interactions of soluble host defense proteins with bacteria and virus in HIV/AIDS. "Crosstalk" was designed as a longitudinal study of host responses along the gastrointestinal (GI) tract and interactions between defense molecules and bacteria in HIV infection and subsequent therapy. PURPOSE: The clinical core formed the infrastructure for the study of the interactions between the proteome, microbiome and innate immune system. The core recruited and retained study subjects, scheduled visits, obtained demographic and medical data, assessed oral health status, collected samples, and guided analysis of the hypotheses. This manuscript presents a well-designed clinical core that may serve as a model for studies that combine clinical and laboratory data. METHODS: Crosstalk was a case-control longitudinal clinical study an initial planned enrollment of 170 subjects. HIV+ antiretroviral naive subjects were followed for 9 visits over 96 weeks and HIV uninfected subjects for 3 visits over 24 weeks. Clinical prevalence of oral mucosal lesions, dental caries and periodontal disease were assessed. RESULTS: During the study, 116 subjects (47 HIV+, 69 HIV-) were enrolled. Cohorts of HIV+ and HIV- were demographically similar except for a larger proportion of women in the HIV- group. The most prevalent oral mucosal lesions were oral candidiasis and hairy leukoplakia in the HIV+ group. DISCUSSION: The clinical core was essential to enable the links between clinical and laboratory data. The study aims to determine specific differences between oral and GI tissues that account for unique patterns of opportunistic infections and to delineate the differences in their susceptibility to infection by HIV and their responses post-HAART.
PMCID:4237510
PMID: 25409430
ISSN: 1932-6203
CID: 1355192

Changes in abundance of oral microbiota associated with oral cancer

Schmidt, Brian L; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M; Queiroz, Erica L S; Nightingale, Kira; Kerr, A Ross; DeLacure, Mark D; Veeramachaneni, Ratna; Olshen, Adam B; Albertson, Donna G
Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.
PMCID:4041887
PMID: 24887397
ISSN: 1932-6203
CID: 1030742

Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to prevent enamel loss after erosive challenges using an intra-oral erosion model

Sullivan, R; Rege, A; Corby, P; Klaczany, G; Allen, K; Hershkowitz, D; Godder, B; Wolff, M
OBJECTIVE:The objective of this study was to assess the ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin' Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to prevent enamel loss from an erosive acid challenge in comparison to a silica-based dentifrice with 1450 ppm fluoride as MFP using an intra-oral erosion model. METHODS:The intra-oral clinical study used a double blind, two-treatment, crossover design. A palatal retainer was used to expose the enamel specimens to the oral environment during the five-day treatment period. The retainer was designed to house three partially demineralized bovine enamel samples. The study population was composed of 24 adults, ages 18 to 70 years. The study consisted of two treatment periods, with a washout period lasting seven (+/- three) days preceding each treatment phase. A silica-based dentifrice without fluoride was used during the washout period. The Test Dentifrice used in this study contained 8% arginine and calcium carbonate (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The treatment period lasted five days, during which the panelists wore the retainer 24 hours a day (except during meals and the ex vivo acid challenges) and brushed with their assigned product while wearing the retainer. The panelists brushed once in the morning and once in the evening each day for one minute, followed by a one-minute swish with the slurry and a rinse with 15 ml of water. The panelists brushed only their teeth and not the specimens directly. There were four ex vivo challenges with 1% citric acid dispersed throughout the day: two in the morning, one in the afternoon, and one in the evening. Mineral loss was monitored by a quantitative light fluorescence (QLF) technique. RESULTS:Twenty-three of 24 subjects successfully completed the study. The one subject who did not complete the study did so for reasons unrelated to the study or products used. The average percent mineral loss for the Test Dentifrice and Control Dentifrice was 9.74 +/- 13.23 and 18.36 +/- 14.14, respectively. The statistical analysis showed that the observed product differences were statistically significant (p < 0.001). CONCLUSION/CONCLUSIONS:The Test Dentifrice with 8% arginine, calcium carbonate, and 1450 ppm fluoride as MFP provided significantly better protection against erosive challenges in comparison to the Control Dentifrice with 1450 ppm fluoride as MFP.
PMID: 24933798
ISSN: 0895-8831
CID: 3133562