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1.
Int Orthod ; 21(4): 100810, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37774499

ABSTRACT

OBJECTIVES: A TiNb alloy wire (GUMMETAL® [GM], Toyota Central R&D Labs, Inc., Nagakute, Japan) was recently developed with unique properties for orthodontic applications. This pilot split-mouth randomized controlled trial compared maxillary canine retraction during space closure using sliding mechanics on GM vs. stainless steel (SS) archwires. METHODS: Subjects who met the inclusion criteria were treated with fixed appliances and maxillary first-premolar extractions between September 2020 and March 2022. After leveling and aligning, maxillary archwires, fabricated by crimping together segments of 0.016×0.022" GM and SS archwires, were placed and canine retraction initiated using nickel-titanium coil springs. Digital models of the maxillary arch were superimposed at 0, 4, 8 and 12 weeks and the amount of canine movement (mm), rate of movement (mm/month), and 3-dimensional changes (rotational, vertical extrusion, tip) were measured and compared statistically. RESULTS: Of the 12 subjects recruited, only six completed the study with a median age of 15.8 years (12.0-17.4 years). At 12 weeks, the median canine retraction was 3.41mm (IQR: 2.10, 4.76) with GM versus 3.71mm (IQR: 1.62, 6.45) with SS. The retraction rate was 1.14mm/month (IQR: 0.69, 1.59) with GM, versus 1.24mm/month (IQR: 0.54, 2.15) with SS. The median rotational, vertical and tip changes of the canine were 7.90̊, 0.59mm and 6.15̊ with GM, and 7.25̊, 0.29mm and 2.05̊ with SS. Intergroup differences with all measurements were not statistically significant. CONCLUSION: No significant differences were found between GM and SS during maxillary canine retraction. GM demonstrated clinical potential for space closure mechanics, however, future larger studies are needed.


Subject(s)
Dental Alloys , Stainless Steel , Humans , Adolescent , Orthodontic Wires , Orthodontic Space Closure/methods , Alloys , Mouth , Titanium , Tooth Movement Techniques/methods , Cuspid
2.
Cranio ; : 1-11, 2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36368042

ABSTRACT

OBJECTIVE: To determine the association between obstructive sleep apnea syndrome (OSAS) and predicted bone mineral density (BMD) in adults presenting for orthodontic treatment. METHODS: This retrospective cross-sectional study included 38 adults divided into OSAS and non-OSAS groups. Using pre-treatment CBCT images, radiographic density (RD) of left and right lateral regions of the 1st cervical vertebrae and dens of the 2nd cervical vertebrae were measured as an indicator for BMD. RESULTS: When controlling for age, sex, and BMI, the mean RD was significantly lower in the OSAS group compared to the non-OSAS group (left CV1: 36.69 ± 84.50 vs. 81.67 ± 93.25 Hounsfield Units [HU], respectively, p = 0.031; right CV1: 30.59 ± 81.18 vs. 74.26 ± 91.81 HU, p = 0.045; dens: 159.25 ± 115.96 vs. 223.94 ± 106.09 HU, p = 0.038). CONCLUSION: Adults with OSAS have lower values for predicted BMD than those without OSAS.

3.
Materials (Basel) ; 15(5)2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35269097

ABSTRACT

The objectives of this study were to (1) to evaluate the shear bond strength (SBS) of two ceramic brackets when new and when rebonded following various bracket base conditioning methods, and (2) to determine bond failure mode relative to bracket base morphology. 100 Symetri ClearTM (SC) and 100 Radiance Plus® (RP) ceramic brackets were bonded to bovine incisors and divided into five groups: one group served as controls and four had brackets rebonded following conditioning by: no surface treatment, sealant, sandblasting, and flame then steam. SBS, adhesive remnant index, and bracket base morphology were evaluated. SBS showed no statistical difference between new and rebonded with no surface treatment or sealant (SC brackets) and with sealant or flame and steam (RP brackets). When comparing SC to RP, SBS was higher with SC, no surface treatment, and sandblasted groups. All groups had varying amounts of adhesive left on the tooth, with the sandblasted group having the most. SEM analysis showed that sandblasting damaged the retention features of bracket bases. In conclusion, when rebonded, the SBS of SC brackets that had no surface treatment and both SC and RP brackets that had sealant showed no significant differences to new brackets. Sandblasting damaged the retention features of SC and RP bracket bases, resulting in low SBS.

4.
Angle Orthod ; 92(2): 213-219, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35168254

ABSTRACT

OBJECTIVES: To compare efficacy of casein phosphopeptide (CPP)-amorphous calcium phosphate (ACP) fluoride varnish and light-curable resin modified glass ionomer fluoride varnish (FV) in preventing white spot lesions and evaluating acid etching prior to CPP-ACPFV application on its efficacy. MATERIALS AND METHODS: Molars and premolars were transected and halves divided into four groups (n = 18/group): (1) resin-modified glass ionomer FV: etched and Clinpro-XT varnish (3M ESPE, Pymble, New South Wales, Australia) application; (2) CPP-ACPFV: MI varnish (GC America, Alsip, IL) application; (3) Etch+CPP-ACPFV: etched and MI varnish application; (4) Control: etched and no surface treatment. To simulate 12 weeks in an intraoral environment, samples were subjected to thermocycling, brushing, and pH cycling. Enamel surface microhardness was evaluated at baseline and after the simulated 12 weeks. Representative samples were also assessed using scanning electron microscopy (SEM). RESULTS: At baseline there was no significant difference in microhardness among groups. After the simulated 12 weeks, all groups showed significant within-group differences (P < .001). Control showed the highest percentage loss of surface microhardness (89%), followed by CPP-ACPFV (58%), RMGIFV (51%), and Etch+CPP-ACPFV (24%). The control group had a significant decrease in microhardness compared to all experimental groups (P < .001). No difference was found between the RMGIFV and CPP-ACPFV varnish groups. The Etch+CPP-ACPFV group had significantly less decrease in microhardness compared to the RMGIFV (P < .001) and CPP-ACPFV groups (P < .001). With SEM, control samples showed signs of enamel surface damage, while experimental groups showed spherical particles on a relatively intact surface. CONCLUSIONS: RMGIFV and CPP-ACPFV are effective in reducing enamel demineralization. Acid etching the enamel surface prior to CPP-ACPFV varnish application increased its efficacy.


Subject(s)
Fluorides , Tooth Demineralization , Calcium Phosphates , Caseins , Dental Enamel , Fluorides, Topical , Humans , Phosphopeptides , Tooth Demineralization/prevention & control
5.
J Am Dent Assoc ; 153(1): 39-49, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34763817

ABSTRACT

BACKGROUND: The purpose of this study was to compare color alterations (ΔE) of white-spot lesions (WSLs) bleached before versus after resin infiltration (RI). METHODS: Using the facial surfaces of bovine maxillary incisors, WSLs were created and the teeth were allocated into 2 groups (n = 45/group): bleach then RI (B-RI group) and RI then bleach (RI-B group). To determine ΔE, Commission Internationale de l'Eclairage L∗ a∗ b∗ (L∗ represents lightness, ranging from black to white [0-100]; a∗ represents green to red chromaticity [-150-+100]; and b∗ represents blue to yellow chromaticity [-100-+150]) measurements were obtained at baseline, after WSL formation, and after RI and bleaching. Representative specimens were evaluated by means of scanning electron microscopy. Statistical analyses included the Mann-Whitney U and Wilcoxon signed rank tests (P ≤ .0016) and repeated measures analysis of variance (P ≤ .05). RESULTS: No differences in ΔE were found comparing B-RI with RI-B groups or when the B-RI group was compared with bleached enamel. A statistically significant difference was found when the RI-B group was compared with bleached enamel (ΔE, 0.81; P < .001), but the difference was deemed not clinically significant. Scanning electron microscopy revealed that bleaching after RI increased surface roughness of the resin. CONCLUSIONS: There were no clinically significant differences in ΔE of WSLs when bleach was applied before or after RI; however, applying bleaching agent after RI roughened the surface of the resin material. PRACTICAL IMPLICATIONS: Results indicate that ΔE were not clinically significantly different between WSLs bleached before versus after RI, although it is best to sequence bleaching before RI therapy, as bleaching after RI roughened the restoration's surface.


Subject(s)
Dental Caries , Tooth Bleaching , Animals , Cattle , Color , Dental Enamel , Humans , Incisor , Resins, Synthetic , Tooth Bleaching/adverse effects
6.
PLoS One ; 16(4): e0243336, 2021.
Article in English | MEDLINE | ID: mdl-33909629

ABSTRACT

A joint analysis of the NCI60 small molecule screening data, their genetically defective genes, and mechanisms of action (MOA) of FDA approved cancer drugs screened in the NCI60 is proposed for identifying links between chemosensitivity, genomic defects and MOA. Self-Organizing-Maps (SOMs) are used to organize the chemosensitivity data. Student's t-tests are used to identify SOM clusters with enhanced chemosensitivity for tumor cell lines with versus without genetically defective genes. Fisher's exact and chi-square tests are used to reveal instances where defective gene to chemosensitivity associations have enriched MOAs. The results of this analysis find a relatively small set of defective genes, inclusive of ABL1, AXL, BRAF, CDC25A, CDKN2A, IGF1R, KRAS, MECOM, MMP1, MYC, NOTCH1, NRAS, PIK3CG, PTK2, RPTOR, SPTBN1, STAT2, TNKS and ZHX2, as possible candidates for roles in chemosensitivity for compound MOAs that target primarily, but not exclusively, kinases, nucleic acid synthesis, protein synthesis, apoptosis and tubulin. These results find exploitable instances of enhanced chemosensitivity of compound MOA's for selected defective genes. Collectively these findings will advance the interpretation of pre-clinical screening data as well as contribute towards the goals of cancer drug discovery, development decision making, and explanation of drug mechanisms.


Subject(s)
Antineoplastic Agents/pharmacology , Computational Biology , Databases, Nucleic Acid , Drug Resistance, Neoplasm , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Neoplasm Proteins , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Drug Screening Assays, Antitumor , Humans , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics
8.
Angle Orthod ; 90(4): 485-490, 2020 07 01.
Article in English | MEDLINE | ID: mdl-33378505

ABSTRACT

OBJECTIVE: To assess the efficacy and efficiency of treatment in adolescents presenting with mild malocclusions, comparing outcomes using clear aligners to fixed appliances. MATERIALS AND METHODS: Patients identified retrospectively and consecutively from one private practice had been treated with either clear aligners (Invisalign, Align Technology, Santa Clara, Calif) or fixed appliances (0.022 Damon, Ormco, Orange, Calif; n = 26/group). Assessments of occlusion were made using the American Board of Orthodontics Discrepancy Index (DI) for initial records and Cast-Radiograph Evaluation (CRE) for final records. Number of appointments, number of emergency visits, and overall treatment time were determined from chart reviews. Data were analyzed using Pearson's correlation, Wilcoxon rank tests, unpaired t-tests, and Chi-square tests, with significance set to P ≤ .05. RESULTS: Pretreatment, the aligner and fixed groups showed no significant difference in overall severity (DI: 11.9 ± 5.3 vs 11.6 ± 4.8) or in any individual DI category. Posttreatment scores showed finishes for the aligner group had fewer discrepancies from ideal relative to the fixed appliance group (CRE: 30.1 ± 8.3 vs 37.0 ± 9.3; P < .01). Patients treated with aligners had fewer appointments (13.7 ± 4.4 vs 19.3 ± 3.6; P < .0001), fewer emergency visits (0.8 ± 1.0 vs 3.6 ± 2.5; P < .0001), and shorter overall treatment time (16.9 ± 5.7 vs 23.4 ± 4.4 months; P < .0001). CONCLUSIONS: Outcomes for treatment of mild malocclusions in adolescents showed equivalent effectiveness of clear aligners compared to fixed appliances, with significantly improved results for clear aligner treatment in terms of tooth alignment, occlusal relations, and overjet. Assessment of the number of appointments, number of emergency visits, and overall treatment time showed better outcomes for treatment with clear aligners.


Subject(s)
Malocclusion , Orthodontic Appliances, Removable , Adolescent , Humans , Malocclusion/therapy , Orthodontic Appliance Design , Orthodontic Appliances, Fixed , Outcome Assessment, Health Care , Retrospective Studies , Treatment Outcome
10.
Orthod Craniofac Res ; 22 Suppl 1: 5-7, 2019 May.
Article in English | MEDLINE | ID: mdl-30801925

ABSTRACT

OBJECTIVE: A third focused workshop explored how to transfer novel findings into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Participants met at the Scottsdale Plaza Resort, 12-16 September 2018 for the Consortium for Orthodontic Advances in Science and Technology 2018 Innovators' Workshop. Thirty speakers and four lunch-hour focus group leaders shared and exchanged information with approximately 45 registered attendees. MATERIAL AND METHODS: This Innovators' Workshop was organized according to five themed sessions which covered: (a) The relevance of genetics, biology and environment to therapeutic outcomes; (b) Application of bioinformatics in craniofacial research; (c) Regeneration with and for orthodontic treatment; (d) Technology in precision orthodontics; and (e) Muscle, joint, and airway: Growth, function and pain. RESULTS: The papers that comprise this supplemental issue exemplify the important outcomes of the 2018 COAST Workshop. In addition, matters identified as important needs include improved understanding of neural, skeletal and muscle tissue crosstalk in early craniofacial growth; standardized methods for three-dimensional radiographic and surface landmark and reference plane identification, measurements and serial superimpositioning techniques for use in the clinic; sharing and making available existing data sets (eg, cone beam computed tomography images, genotype-phenotype data); evidence of the usefulness and effectiveness of new devices; guidelines of what to measure to characterize the airway; more information about the influences of the soft tissues on craniofacial morphology; and information about effective digital work flows applied to clinical and educational settings. CONCLUSIONS: Progress in bridging the biology-technology gap has identified new needs for improvements in orthodontics and craniofacial care.


Subject(s)
Orthodontics , Cone-Beam Computed Tomography , Imaging, Three-Dimensional
11.
Angle Orthod ; 89(3): 438-445, 2019 05.
Article in English | MEDLINE | ID: mdl-30653333

ABSTRACT

OBJECTIVES: To assess the effectiveness and efficiency of ultraviolet (UV) illumination compared to conventional white light in the detection of fluorescent-tagged adhesive remnants during orthodontic debonding. MATERIALS AND METHODS: Orthodontic brackets were bonded to extracted human premolars using one of two bonding resins having fluorescent properties (Pad Lock, Reliance Orthodontics, Itasca, Ill; Opal Bond MV, Opal Orthodontics, South Jordan, Utah; n = 40 each). The brackets were then debonded and, in each adhesive group, half the teeth had the remaining adhesive resin removed under illumination using the operatory light and the other half using a UV (395 nm) light emitting diode (LED) flashlight (n = 20/group). Time for teeth cleanup was recorded. Follow-up images were obtained under a dissecting microscope using UV illumination, and the surface area of adhesive remnants was calculated. Effectiveness of adhesive removal was also assessed using scanning electron microscopy imaging. Analysis of variance and Kruskal-Wallis tests were used to analyze time and adhesive remnants, respectively. RESULTS: Assessment using the dissecting microscope found groups using UV light during adhesive removal had statistically significantly lower amounts of adhesive remnants than groups using white light (P ≤ .01). Time for adhesive removal was significantly lower with Opal Bond MV adhesive using UV light when compared with the white light (P ≤ .01). Assessment by scanning electron microscopy showed that thin remnants of adhesive (<2 µm) remained undetected by UV illumination. CONCLUSIONS: UV light is more effective and tends to be more efficient than white light in the detection of fluorescent adhesive during orthodontic debonding. Although there are limitations, the use of UV LED lighting is a practical tool that aids in adhesive detection.


Subject(s)
Dental Bonding , Dental Debonding , Orthodontic Brackets , Ultraviolet Rays , Dental Cements , Dental Enamel , Humans , Jordan , Materials Testing , Resin Cements , Surface Properties
12.
Cleft Palate Craniofac J ; 56(7): 902-907, 2019 08.
Article in English | MEDLINE | ID: mdl-30514093

ABSTRACT

OBJECTIVE: To assess weight gain of infants with cleft lip and/or palate (CL ± P) treated with nasoalveolar molding (NAM). DESIGN: Retrospective, case-control chart review. SETTING: Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon. PATIENTS, PARTICIPANTS: Infants with nonsyndromic CL ± P and noncleft controls. INTERVENTIONS: Prior to primary lip surgery, NAM was either included (+NAM) or not included (-NAM) in the cleft treatment protocol. MAIN OUTCOME MEASURE(S): Weight gain and percentage weight gain relative to initial weight were compared among +NAM, -NAM, and control groups from birth to 7 months and from birth to 36 months. RESULTS: Comparing +NAM and -NAM groups, no significant difference in weight or percentage weight gain was found in either time window. Compared to controls, from birth to 7 months, both CL ± P groups weighed less (P < .001), while percentage weight gain was greater for the +NAM (P < .001) and did not differ for -NAM. From birth to 36 months relative to controls, weight for +NAM showed no significant difference and -NAM weighed less (P < .01), while percentage weight gain was greater for both CL ± P groups (P < .001). CONCLUSIONS: Comparisons of CL ± P infants treated with and without NAM showed that with the NAM appliance, despite its added complexity, there was no adverse impact on weight gain. Comparisons to noncleft, control infants suggests that NAM treatment may have a beneficial impact on weight gain.


Subject(s)
Cleft Lip , Cleft Palate , Weight Gain , Case-Control Studies , Child , Cleft Lip/surgery , Cleft Palate/surgery , Humans , Infant , Nose/surgery , Retrospective Studies
13.
Int J Oral Maxillofac Implants ; 33(6): 1296-1304, 2018.
Article in English | MEDLINE | ID: mdl-30427960

ABSTRACT

PURPOSE: To investigate cone beam computed tomography (CBCT) accuracy in measuring facial bone height and detecting dehiscence and fenestration defects around teeth. MATERIALS AND METHODS: Patients who were treatment planned for periodontal flap or dental implant surgeries were enrolled (n = 25). CBCT imaging (Carestream CS 9300) was obtained at 0.09-mm voxels (n = 10 patients, 23 teeth) and at 0.18-mm voxels (n = 15 patients, 33 teeth). Facial bone height measurements, from cusp tip to crest of bone height along the long axis of the tooth, and presence or absence of dehiscence or fenestration defects were recorded from CBCT images in triplicates independently by two examiners. The corresponding clinical measurements were made at the time of surgery. Comparisons of CBCT and clinical measurements were made using paired t tests for teeth: anterior and posterior, maxillary and mandibular, with or without restorations, or root canal therapy. Level of agreement between investigators was assessed by concordance correlation coefficients (CCC), Pearson's correlation coefficient (PCC), and Cohen's Kappa. RESULTS: Comparing mean CBCT and clinical measurements, statistically significant differences were noted for 0.09-mm and 0.18-mm voxel sizes, for anterior and posterior teeth, for maxillary and mandibular teeth, for teeth with or without restorations, and for teeth without root canal therapy (P < .05). Clinical and CBCT measurements were similar for teeth with crowns and with root canal therapy (P > .05). CBCT measurements underestimated mean facial bone height from 0.33 ± 0.78 to 0.88 ± 1.14 mm (mean ± SD) and absolute facial bone height values from 0.56 ± 0.35 to 1.08 ± 0.92 mm. Intraexaminer and interexaminer reliability for measuring facial bone height ranged from poor to substantial (PCC = 0.78 to 0.97 and CCC = 0.63 to 0.96, respectively). Interexaminer reliability for detection of dehiscence and fenestration defects ranged from poor to moderate (Cohen's Kappa = -0.09 to 0.66). CONCLUSION: CBCT imaging underestimated facial bone height and overestimated the presence of dehiscence and fenestration defects.


Subject(s)
Alveolar Bone Loss/diagnostic imaging , Alveolar Process/diagnostic imaging , Cone-Beam Computed Tomography/methods , Dental Implantation, Endosseous/methods , Dental Implants , Maxilla/diagnostic imaging , Adult , Female , Humans , Incisor , Male , Mandible , Reproducibility of Results
14.
Angle Orthod ; 87(6): 834-840, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28841034

ABSTRACT

OBJECTIVE: To evaluate the effect of different curing modes available in a dental light-curing unit on degree of conversion (DC) of a composite photoactivated under a metal orthodontic bracket. MATERIALS AND METHODS: The average irradiance and total energy delivered by three curing modes (standard, high, and extra power) of a multiwave LED unit (Valo Cordless, Ultradent Products, South Jordan, Utah) were measured using the longest time available for each mode (20, 4, and 3 seconds, respectively). Brackets (n = 3/group) were bonded to molar epoxy resin replicas using each curing mode. Mesiodistal sections, 0.5 mm thick, were assessed using an infrared spectrometer microscope. Spectra of composite beneath the brackets were sequentially collected using the mapping tool in near-infrared (NIR)-transmittance mode. Composite conversion was mapped between the mesial and distal edges of the bracket base using 400-µm steps for a total of 10 measurements per specimen. Data from irradiance and total energy were analyzed by one-way ANOVA, while data of DC were analyzed with two-way repeated measures ANOVA (α = 0.05). RESULTS: The highest DC values were observed for standard power (mean 56%, P < .05), while no difference was observed between high (50%) and extra power (49%) modes. Regarding the site of measurement, higher DC was observed close to the bracket edges (52%, P < .05). CONCLUSIONS: The use of high irradiance for a short time slightly reduced the DC. The small magnitude of reduction suggests that use of a high irradiance protocol is a clinically valid approach when bonding metal brackets.


Subject(s)
Curing Lights, Dental , Orthodontic Brackets , Polymerization , Humans , In Vitro Techniques , Metals , Orthodontic Appliance Design , Time Factors , Treatment Outcome
15.
PLoS One ; 12(8): e0181991, 2017.
Article in English | MEDLINE | ID: mdl-28792525

ABSTRACT

A novel data mining procedure is proposed for identifying potential pathway-gene biomarkers from preclinical drug sensitivity data for predicting clinical responses to erlotinib or sorafenib. The analysis applies linear ridge regression modeling to generate a small (N~1000) set of baseline gene expressions that jointly yield quality predictions of preclinical drug sensitivity data and clinical responses. Standard clustering of the pathway-gene combinations from gene set enrichment analysis of this initial gene set, according to their shared appearance in molecular function pathways, yields a reduced (N~300) set of potential pathway-gene biomarkers. A modified method for quantifying pathway fitness is used to determine smaller numbers of over and under expressed genes that correspond with favorable and unfavorable clinical responses. Detailed literature-based evidence is provided in support of the roles of these under and over expressed genes in compound efficacy. RandomForest analysis of potential pathway-gene biomarkers finds average treatment prediction errors of 10% and 22%, respectively, for patients receiving erlotinib or sorafenib that had a favorable clinical response. Higher errors were found for both compounds when predicting an unfavorable clinical response. Collectively these results suggest complementary roles for biomarker genes and biomarker pathways when predicting clinical responses from preclinical data.


Subject(s)
Antineoplastic Agents/therapeutic use , Data Mining/methods , Erlotinib Hydrochloride/therapeutic use , Neoplasms/genetics , Neoplasms/metabolism , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Biomarkers, Pharmacological/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cluster Analysis , Databases, Factual , Gene Expression Regulation, Neoplastic/drug effects , Humans , Linear Models , Microarray Analysis , Neoplasms/drug therapy , Niacinamide/therapeutic use , Prognosis , Sorafenib , Treatment Outcome
16.
BMC Microbiol ; 15: 259, 2015 Nov 06.
Article in English | MEDLINE | ID: mdl-26545875

ABSTRACT

BACKGROUND: Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered. RESULTS: The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt. CONCLUSIONS: These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.


Subject(s)
Burkholderia mallei/immunology , Burkholderia pseudomallei/immunology , Chemokines/genetics , Macrophages/immunology , Macrophages/microbiology , Actins/metabolism , Animals , Burkholderia mallei/isolation & purification , Burkholderia mallei/pathogenicity , Burkholderia pseudomallei/isolation & purification , Burkholderia pseudomallei/pathogenicity , Gene Expression Regulation , Giant Cells/metabolism , Immunity, Innate , Macrophages/cytology , Mice , RAW 264.7 Cells
17.
PLoS One ; 10(7): e0127433, 2015.
Article in English | MEDLINE | ID: mdl-26132924

ABSTRACT

Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE) and Sanger Cancer Genome Project (CGP). The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a) evaluate drug responses of compounds with similar mechanism of action (MOA), b) examine measures of gene expression (GE), copy number (CN) and mutation status (MUT) biomarkers, combined with gene set enrichment analysis (GSEA), for hypothesizing biological processes important for drug response, c) conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d) assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.


Subject(s)
Biomarkers, Tumor , Data Mining , Genomics , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cluster Analysis , Computational Biology/methods , DNA Copy Number Variations , Databases, Genetic , Drug Discovery , Drug Screening Assays, Antitumor , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Genomics/methods , Humans , Mutation , Neoplasms/drug therapy , Neoplasms/genetics
18.
J Nat Prod ; 77(11): 2475-80, 2014 Nov 26.
Article in English | MEDLINE | ID: mdl-25338277

ABSTRACT

Bioinformatic analysis of data from the NCI-60 cell cytotoxicity screen revealed a subset of extracts that showed selective cytotoxic activity toward human colon carcinoma cell lines. Bioassay-guided fractionation of a colon cancer selective extract from a Philippines collection of the marine sponge Corticium niger provided two new steroidal alkaloids, plakinamines N (1) and O (2), along with two known compounds of the plakinamine class (3, 4). The structures of these compounds were elucidated by interpretation of combined MS and NMR spectroscopic data. Plakinamines N (1), O (2), and J (4) were tested for antiproliferative activity in the NCI-60 screen, and they showed enhanced inhibitory effects against all of the colon cell lines with mean GI50 values of 11.5, 2.4, and 1.4 µM, respectively.


Subject(s)
Alkaloids/isolation & purification , Porifera/chemistry , Steroids/isolation & purification , Steroids/pharmacology , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Colonic Neoplasms/drug therapy , Drug Screening Assays, Antitumor , Humans , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Philippines , Steroids/chemistry
19.
Angle Orthod ; 84(4): 607-14, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24555689

ABSTRACT

OBJECTIVE: To measure and compare bracket transfer accuracy of five indirect bonding (IDB) techniques. MATERIALS AND METHODS: Five IDB techniques were studied: double polyvinyl siloxane (double-PVS), double vacuum-form (double-VF), polyvinyl siloxane vacuum-form (PVS-VF), polyvinyl siloxane putty (PVS-putty), and single vacuum-form (single-VF). Brackets were bonded on 25 identical stone working models. IDB trays were fabricated over working models (n  =  5 per technique) to transfer brackets to another 25 identical stone patient models. The mesiodistal (M-D), occlusogingival (O-G), and faciolingual (F-L) positions of each bracket were measured on the working and patient models using digital photography (M-D, O-G) and calipers (F-L). Paired t-tests were used to compare bracket positions between working and patient models, and analysis of variance was used to compare bracket transfer accuracy among the five techniques. RESULTS: Between the working and patient models, double-VF had the most teeth with significant differences (n  =  6) and PVS-VF the fewest (n  =  1; P < .05). With one exception, all significant differences were ≤0.26 mm and most (65%) were ≤0.13 mm. When the techniques were compared, bracket transfer accuracy was similar for double-PVS, PVS-putty, and PVS-VF, whereas double-VF and single-VF showed significantly less accuracy in the O-G direction. CONCLUSIONS: Although overall differences in bracket position were relatively small, silicone-based trays had consistently high accuracy in transferring brackets, whereas methods that exclusively used vacuum-formed trays were less consistent.


Subject(s)
Dental Bonding/methods , Orthodontic Brackets , Dental Bonding/instrumentation , Dental Bonding/statistics & numerical data , Humans , Image Processing, Computer-Assisted/methods , Models, Dental , Photography, Dental/methods , Polyvinyls/chemistry , Resin Cements/chemistry , Siloxanes/chemistry , Tooth/anatomy & histology , Vacuum , Vinyl Compounds/chemistry
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