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1.
JDR Clin Trans Res ; 8(3): 215-223, 2023 07.
Article in English | MEDLINE | ID: mdl-35446163

ABSTRACT

OBJECTIVE: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. METHODS: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013-2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)-recommended level of 0.7 ppm. RESULTS: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%-47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%-42%) greater dfs and 10% (95% CI, 2%-20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. CONCLUSIONS: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. KNOWLEDGE TRANSFER STATEMENT: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.


Subject(s)
Dental Caries , Fluorides , Adolescent , Humans , Child , Fluorides/adverse effects , Dental Caries/epidemiology , Dental Caries/etiology , Dental Caries/prevention & control , Nutrition Surveys , Cross-Sectional Studies , Sugars
2.
JDR Clin Trans Res ; 6(4): 368-381, 2021 10.
Article in English | MEDLINE | ID: mdl-33030085

ABSTRACT

OBJECTIVES: To conduct a systematic review and meta-analysis to assess whether individuals with nonsyndromic orofacial clefts (OCs) display a higher frequency of dental anomalies (DAs) when compared with individuals without OCs. METHODS: A literature search of indexed databases (PubMed, Cochrane, Web of Science, Embase, Scopus, and LILACS) was conducted without language restriction up to and including February 1, 2020. Cross-referencing was used to further identify articles. Several cleft teams across the United States and Europe were contacted to obtain unpublished data. The eligibility criteria were observational studies with original data that statistically compared individuals with OC without syndromes and those without OC on any type of DA in primary and/or permanent dentition. Random effects meta-analysis through the Mantel-Haenszel estimator was used to evaluate the association between OC and DA based on odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The literature search generated 933 records, and 75 full-text articles were reviewed. Twenty-six studies encompassing 15,213 individuals met the inclusion criteria. The meta-analysis revealed statistically significant associations between OC and agenesis (OR, 14.2; 95% CI, 9.4 to 21.3), supernumerary teeth (OR, 5.7; 95% CI, 3.3 to 9.7), developmental enamel defects (OR, 5.6; 95% CI, 3.5 to 9.0), microdontia (OR, 14.8; 95% CI, 4.0 to 54.6), peg-shaped anterior teeth (OR, 12.2; 95% CI, 3.6 to 41.2), taurodontism (OR, 1.7; 95% CI, 1.0 to 2.7), tooth malposition and/or transposition (OR, 5.6; 95% CI, 2.8 to 11.5), tooth rotation (OR, 3.2; 95% CI, 1.3 to 8.2), and tooth impaction (OR, 3.6; 95% CI, 1.1 to 12.2). The OR estimates of the reviewed studies exhibited significant heterogeneity (P < 0.0001). No association was observed between OC and fusion and/or gemination. CONCLUSION: Within the limitations of this study, the available evidence suggests that individuals with OCs are more likely to present with a range of DAs than their unaffected peers. KNOWLEDGE TRANSFER STATEMENT: The findings of the current review suggest that individuals with orofacial clefts (OCs) are more likely to present with a range of dental anomalies than their unaffected peers. Understanding the association between OCs and dental anomalies is essential in guiding clinicians during treatment-planning procedures and is important in raising our awareness of the possible need for future dental treatment for patients with OCs.


Subject(s)
Cleft Lip , Cleft Palate , Tooth Abnormalities , Tooth, Supernumerary , Cleft Lip/epidemiology , Cleft Palate/epidemiology , Dentition, Permanent , Humans , Tooth Abnormalities/epidemiology
3.
Space Sci Rev ; 216(8): 137, 2020.
Article in English | MEDLINE | ID: mdl-33268910

ABSTRACT

The Mars 2020 Perseverance rover is equipped with a next-generation engineering camera imaging system that represents an upgrade over previous Mars rover missions. These upgrades will improve the operational capabilities of the rover with an emphasis on drive planning, robotic arm operation, instrument operations, sample caching activities, and documentation of key events during entry, descent, and landing (EDL). There are a total of 16 cameras in the Perseverance engineering imaging system, including 9 cameras for surface operations and 7 cameras for EDL documentation. There are 3 types of cameras designed for surface operations: Navigation cameras (Navcams, quantity 2), Hazard Avoidance Cameras (Hazcams, quantity 6), and Cachecam (quantity 1). The Navcams will acquire color stereo images of the surface with a 96 ∘ × 73 ∘ field of view at 0.33 mrad/pixel. The Hazcams will acquire color stereo images of the surface with a 136 ∘ × 102 ∘ at 0.46 mrad/pixel. The Cachecam, a new camera type, will acquire images of Martian material inside the sample tubes during caching operations at a spatial scale of 12.5 microns/pixel. There are 5 types of EDL documentation cameras: The Parachute Uplook Cameras (PUCs, quantity 3), the Descent stage Downlook Camera (DDC, quantity 1), the Rover Uplook Camera (RUC, quantity 1), the Rover Descent Camera (RDC, quantity 1), and the Lander Vision System (LVS) Camera (LCAM, quantity 1). The PUCs are mounted on the parachute support structure and will acquire video of the parachute deployment event as part of a system to characterize parachute performance. The DDC is attached to the descent stage and pointed downward, it will characterize vehicle dynamics by capturing video of the rover as it descends from the skycrane. The rover-mounted RUC, attached to the rover and looking upward, will capture similar video of the skycrane from the vantage point of the rover and will also acquire video of the descent stage flyaway event. The RDC, attached to the rover and looking downward, will document plume dynamics by imaging the Martian surface before, during, and after rover touchdown. The LCAM, mounted to the bottom of the rover chassis and pointed downward, will acquire 90 ∘ × 90 ∘ FOV images during the parachute descent phase of EDL as input to an onboard map localization by the Lander Vision System (LVS). The rover also carries a microphone, mounted externally on the rover chassis, to capture acoustic signatures during and after EDL. The Perseverance rover launched from Earth on July 30th, 2020, and touchdown on Mars is scheduled for February 18th, 2021.

4.
J Dent Res ; 99(11): 1262-1269, 2020 10.
Article in English | MEDLINE | ID: mdl-32579872

ABSTRACT

Laboratory studies show that bisphenol A (BPA) leaches from bisphenol A-glycidyl methacrylate (bisGMA)-based dental materials. We aimed to quantify the extent to which children are exposed to BPA from dental treatment with bisGMA materials, by amount of treatment and type of sedation. We hypothesized that posttreatment urinary BPA (uBPA) concentrations would be higher among patients with more surfaces treated with bisGMA-based materials and among patients receiving general anesthesia compared with pretreatment concentrations. We conducted a prospective cohort study in 211 children, 4 to 12 y old, who had no prior resin-based dental treatment. We measured uBPA concentrations twice before treatment and at 2 d and 1, 4, and 16 wk posttreatment. We abstracted treatment data (surfaces treated) from the chart. We generated descriptive statistics and compared pre- and posttreatment uBPA concentrations using generalized estimating equations. Participants were 51% female, 46% non-White, and 74% publicly insured. The median age was 6 y. The mean number of tooth surfaces exposed to BisGMA materials (composites/sealants) was 7.5 (SD 5.3). Overall, uBPA concentrations were 86% higher (95% confidence interval [CI] 42% to 143%, P < 0.001) at 2 d posttreatment compared with pretreatment concentrations. The uBPA concentrations 2 d posttreatment versus pretreatment tended to be higher (112%, 95% CI 53% to 194%) among those receiving treatment on >4 surfaces than those receiving treatment on ≤4 surfaces (50%, 95% CI -2% to 130%). Two days after treatment, uBPA was significantly higher than pretreatment concentrations in children receiving nitrous oxide but not in those receiving general anesthesia. Among all findings, uBPA concentrations returned to baseline by 4 wk. Children experience short-term increases in BPA from dental treatment. The impact of relatively high, short-term BPA exposure on child health is unknown. Given the widespread use of BisGMA-based dental materials and that chronic low-dose BPA exposure may adversely affect child health, strategies that minimize BPA exposure could potentially improve child health.


Subject(s)
Benzhydryl Compounds , Phenols , Benzhydryl Compounds/adverse effects , Bisphenol A-Glycidyl Methacrylate , Child , Female , Humans , Male , Prospective Studies
5.
JDR Clin Trans Res ; 4(2): 106-115, 2019 04.
Article in English | MEDLINE | ID: mdl-30931707

ABSTRACT

INTRODUCTION: Dental composite restorations and dental sealants containing bisphenol A glycidyl methacrylate (BisGMA) are commonly used materials in dentistry. Bisphenol A (BPA) is used to manufacture BisGMA and can be a by-product in BisGMA-based dental materials. BPA is an endocrine-disrupting chemical that may affect reproductive, psychological, cognitive, and endocrine-related health. We conducted a systematic review of clinical studies that measured urinary BPA (uBPA) concentrations before and after dental treatment to evaluate the extent to which individuals are exposed to BPA from dental treatment. METHODS: Eligibility included studies that measured uBPA concentrations before and after dental treatment with any type of resin-based dental material. We searched PubMed, Cochrane, Web of Science, Virtual Health Library, Science Direct, ProQuest, and Clinical Trials with no date or language restrictions to identify published studies. We summarized eligible studies across participant characteristics, amount of treatment, and time of follow-up measures. Because methods of measuring uBPA varied, our primary outcome was the direction and percentage change between baseline and 24 h posttreatment and at later time points as available. RESULTS: We identified 1,190 abstracts and 7 eligible studies: 4 in children and 3 in adults. In all studies, BPA concentrations increased 24 h after treatment. The 2 studies with the largest sample sizes found statistically significant increases >40% in uBPA concentrations at 24 h posttreatment (both P values <0.01). The 1 study to examine uBPA concentrations beyond 1 mo posttreatment found that concentrations returned to baseline by 14 d after treatment and remained at baseline 6 mo after treatment. CONCLUSIONS: Our findings suggest that uBPA concentrations increase 24 h after dental treatment. One study showed that uBPA concentrations return to baseline by 14 d. Additional research is needed to determine the magnitude of change from pre- to post-dental treatment and the trajectory of uBPA concentrations posttreatment. KNOWLEDGE TRANSFER STATEMENT: BPA is an endocrine-disrupting chemical that may have negative human health effects. Our findings suggest that urinary BPA concentrations increase in the short term after dental treatment. The extent to which such an increase may affect the health of patients remains an open question, particularly since there are no established thresholds for safety or harm related to BPA exposure.


Subject(s)
Benzhydryl Compounds , Phenols , Adult , Bisphenol A-Glycidyl Methacrylate , Child , Humans , Pit and Fissure Sealants
6.
Nutr Diabetes ; 7(5): e277, 2017 May 15.
Article in English | MEDLINE | ID: mdl-28504709

ABSTRACT

BACKGROUND/OBJECTIVES: Successful Type 2 diabetes management requires adopting a high nutrient-density diet made up of food items that both meet dietary needs and preferences and can be feasibly obtained on a regular basis. However, access to affordable, nutrient-dense foods often is lacking in poorer neighbourhoods. Therefore, low food security should directly impair glucose control, even when patients have full access to and utilize comprehensive medical management. The present study sought to determine whether food security is related longitudinally to glucose control, over-and-above ongoing medication management, among Type 2 diabetes patients receiving comprehensive care at a Midwestern multi-site federally qualified health centre (FQHC). SUBJECTS/METHODS: In this longitudinal observational study, we completed a baseline assessment of patients' food security (using the US Household Food Security Module), demographics (via Census items), and diabetes history/management (using a structured clinical encounter form) when patients began receiving diabetes care at the health centre. We then recorded those patients' A1C levels several times during a 24-month follow-up period. Three hundred and ninety-nine patients (56% with low food security) had a baseline A1c measurement; a subsample of 336 (median age=52 years; 56% female; 60% Hispanic, 27% African American, and 9% White) also had at least one follow-up A1c measurement. RESULTS: Patients with lower (vs higher) food security were more likely to be on insulin and have higher A1c levels at baseline. Moreover, the disparity in glucose control by food security status persisted throughout the next 2 years. CONCLUSIONS: Although results were based on one multi-site FQHC, potentially limiting their generalizability, they seem to suggest that among Type 2 diabetes patients, low food security directly impairs glucose control-even when patients receive full access to comprehensive medical management-thereby increasing their long-term risks of high morbidity, early mortality, and high health-care utilization and cost.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Food Supply , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Primary Health Care , Safety-net Providers , Adult , Diabetes Mellitus, Type 2/blood , Disease Management , Female , Glycated Hemoglobin/analysis , Humans , Longitudinal Studies , Male , Middle Aged , Patient Acceptance of Health Care , United States
7.
Analyst ; 141(16): 4902-11, 2016 Aug 02.
Article in English | MEDLINE | ID: mdl-27314130

ABSTRACT

Multi-modal recording describes the simultaneous collection of information across distinct domains. Compared to isolated measurements, such studies can more easily determine relationships between varieties of phenomena. This is useful for neurochemical investigations which examine cellular activity in response to changes in the local chemical environment. In this study, we demonstrate a method to perform simultaneous patch clamp measurements with fast-scan cyclic voltammetry (FSCV) using optically isolated instrumentation. A model circuit simulating concurrent measurements was used to predict the electrical interference between instruments. No significant impact was anticipated between methods, and predictions were largely confirmed experimentally. One exception was due to capacitive coupling of the FSCV potential waveform into the patch clamp amplifier. However, capacitive transients measured in whole-cell current clamp recordings were well below the level of biological signals, which allowed the activity of cells to be easily determined. Next, the activity of medium spiny neurons (MSNs) was examined in the presence of an FSCV electrode to determine how the exogenous potential impacted nearby cells. The activities of both resting and active MSNs were unaffected by the FSCV waveform. Additionally, application of an iontophoretic current, used to locally deliver drugs and other neurochemicals, did not affect neighboring cells. Finally, MSN activity was monitored during iontophoretic delivery of glutamate, an excitatory neurotransmitter. Membrane depolarization and cell firing were observed concurrently with chemical changes around the cell resulting from delivery. In all, we show how combined electrophysiological and electrochemical measurements can relate information between domains and increase the power of neurochemical investigations.

8.
JDR Clin Trans Res ; 1(3): 226-233, 2016 Oct.
Article in English | MEDLINE | ID: mdl-28879242

ABSTRACT

Racial disparities in how pain is treated in the emergency department (ED) for toothache have not been reported. Due to increasing reliance on EDs for dental care, the authors investigated whether race/ethnicity and insurance type are associated with treatment for toothache pain. The authors conducted a nationally representative cross-sectional study of ED toothache visits by adults (19 to 64 y old), using the 2008-2010 National Hospital Ambulatory Medical Care Survey. Multinomial regression models accounted for the complex survey design. Outcomes were pain medicines received: none, nonopioid only, or opioids. After adjusting for sociodemographic factors, black patients had 1.99 greater odds (P < 0.005) than white patients of receiving only a nonopioid pain medicine for toothache. Visits made by patients on Medicare, Medicaid, uninsured, or "other" insurance status had greater odds than the privately insured of receiving only a nonopioid pain medicine rather than an opioid (odds ratios, respectively: 4.8, P < 0.001; 2.1, P ≤ 0.001; 2.3, P < 0.01; and 4.1, P < 0.001). Blacks are less likely than whites to receive opioids in the ED for a toothache, even with similar levels of pain. Nonprivately insured patients have lower odds than the privately insured to receive opioids for toothache pain. A better understanding of the etiology of these disparities could lead to directed interventions. Knowledge Transfer Statement: This study presents findings novel to the body of pain and oral health care literature. Because there is an increasing reliance on the emergency department to address dental pain, disparities in how toothache pain is treated will be of great interest to a growing number of Americans, clinicians, and policy makers.

9.
Community Ment Health J ; 50(8): 896-902, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24838373

ABSTRACT

The concept of recovery can be operationalized from either the point of view of the consumer or from the perspective of the provider of services. The Recovery Markers Inventory (RMI) was created to assess recovery-related factors (i.e., actions/events associated with consumer's recovery) from the provider's perspective. Evidence, which established the psychometric properties of the RMI, was obtained through the use of: (a) construct validity (i.e., confirmatory factor analysis and Rasch principal components analysis of residuals); (b) concurrent validity (i.e., the calculation of Pearson correlations between the RMI and other recovery-oriented instruments); and (c) reliability (i.e., Rasch Partial Credit models). Evidence presented in this article shows that the RMI scale is unidimensional, has an adequate level of correlation, and acceptable reliability. The current analysis provides evidence to support the RMI as a valid, reliable measure of recovery-related factors, which can complement consumer based instruments in the assessment of changes in recovery.


Subject(s)
Mental Disorders/rehabilitation , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/standards , Surveys and Questionnaires/standards , Treatment Outcome , Adolescent , Adult , Aged , Aged, 80 and over , Attitude of Health Personnel , Community Mental Health Centers , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Patient Outcome Assessment , Psychometrics , Reproducibility of Results , United States , Young Adult
10.
J Dent Res ; 92(12): 1089-94, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24097855

ABSTRACT

Little is known about oral clefts in developing countries. We aimed to identify micronutrient-related and environmental risk factors for oral clefts in Thailand. We tested hypotheses that maternal exposure during the periconceptional period to multivitamins or liver consumption would decrease cleft lip with or without cleft palate (CL ± P) risk and that menstrual regulation supplements would increase CL ± P risk. We conducted a multisite hospital-based case-control study in Thailand. We enrolled cases with CL ± P and 2 live births as controls at birth from the same hospital. Mothers completed a questionnaire. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Eighty-six cases and 172 controls were enrolled. Mothers who took a vitamin (adjusted OR, 0.39; 95% CI: 0.16, 0.94) or ate liver (adjusted OR, 0.26; 95% CI: 0.12, 0.57) were less likely than those who did not to have an affected child. Mothers who took a menstrual regulation supplement were more likely than mothers who did not to have an affected child. Findings did not differ for infants with a family history of other anomalies or with isolated CL ± P. If replicated, our finding that liver decreases CL ± P risk could offer a low-cost primary prevention strategy.


Subject(s)
Cleft Lip/etiology , Cleft Palate/etiology , Micronutrients/analysis , Animals , Calcium/therapeutic use , Case-Control Studies , Common Cold/complications , Contraceptive Agents, Female/therapeutic use , Developing Countries , Diabetes Complications , Environment , Female , Folic Acid/therapeutic use , Humans , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Iron/therapeutic use , Male , Meat , Preconception Care , Risk Factors , Sex Factors , Swine , Thailand , Tretinoin/therapeutic use , Vitamin A/therapeutic use , Vitamin B Complex/therapeutic use , Vitamins/therapeutic use
11.
Genes Immun ; 13(6): 458-60, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22551723

ABSTRACT

There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤ 1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN ≥ 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.


Subject(s)
Gene Deletion , Receptors, IgG/genetics , Scleroderma, Systemic/genetics , Scleroderma, Systemic/immunology , Autoantibodies/blood , Base Sequence , Case-Control Studies , Centromere/immunology , DNA Copy Number Variations , DNA Probes/genetics , DNA Topoisomerases, Type I/immunology , Europe , GPI-Linked Proteins/genetics , Gene Dosage , Genetic Association Studies , Humans , Risk Factors , Scleroderma, Diffuse/genetics , Scleroderma, Diffuse/immunology , Scleroderma, Limited/genetics , Scleroderma, Limited/immunology , White People/genetics
12.
Br J Radiol ; 84(999): 216-20, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20959368

ABSTRACT

OBJECTIVE: Many "guideline-development studies" have presented the sensitivity (SN) and specificity (SP) of a new decision tool to describe the potential improvements in utilisation of imaging techniques as a result of adopting the new guideline. However, SN and SP are measures designed to assess how well a new guideline compares with a gold standard. These measures do not evaluate how many patients with a positive test actually have the disease; nor do they evaluate how many patients with a negative test do not have the disease. To evaluate these characteristics of a decision tool, other measures, namely the positive predictive value (PPV) and negative predictive value (NPV), should be calculated. This report highlights some of the main methodological challenges in interpretation of the studies that attempt to evaluate the development of an imaging guideline and the effectiveness of an imaging guideline in real world practice. METHODS: We define four key measures of a decision tool: SN, SP, PPV and NPV. Using data from two hypothetical populations, we explain how these measures can be calculated and interpreted. We place special emphasis on the purpose of and differences between the SN-SP and PPV-NPV. RESULTS: Borrowing information from two studies, we demonstrate how these measures should be used in the radiology healthcare services research to evaluate decision guidelines. CONCLUSION: The use of appropriate measures for the specific question at hand will ensure the guidelines are useful, safe, cost reducing and effective clinical tools.


Subject(s)
Guideline Adherence/standards , Patient Care Management/standards , Practice Guidelines as Topic , Sensitivity and Specificity , Tomography, X-Ray Computed/standards , Craniocerebral Trauma/diagnostic imaging , Decision Support Techniques , Female , Humans , Male , Risk Assessment
14.
Ann Rheum Dis ; 67(3): 409-13, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17604289

ABSTRACT

OBJECTIVE: There is increasing evidence that gene copy-number variation influences phenotypic variation. Chemokine ligand 3-like 1 (CCL3L1) is encoded by a variable copy-number gene, and binds to several pro-inflammatory cytokine receptors, including chemokine receptor 5 (CCR5). Considering lymphocyte recruitment by beta-chemokines is a feature of autoimmunity, and that the CCR5Delta32 variant is associated with protection to rheumatoid arthritis (RA), we hypothesised that CCL3L1 copy-number influences susceptibility to RA and type 1 diabetes (T1D). METHODS: We measured CCL3L1 copy-number in 1136 RA cases from New Zealand (NZ) and the UK, 252 NZ T1D cases and a total of 1470 controls. All subjects were ancestrally Caucasian. RESULTS: A copy-number higher than 2 (the most common copy number) was a risk factor for RA in the NZ cohort (odds ratio (OR) 1.34, 95% CI 1.08-1.66, p = 0.009) but not the smaller UK RA cohort (OR 1.09, 95% CI 0.75-1.60, p = 0.643). There was evidence for association in the T1D cohort (OR 1.46, 95% CI 0.98-2.20, p = 0.064) and in the combined RA/T1D cohort (OR 1.30, 95% CI 1.00-1.54, p = 0.003). Genetic interaction between CCL3L1 dosage and CCR5 genotype was found; the increased genetic risk conferred by higher CCL3L1 copy-number was ablated by a dysfunctional CCR5 (CCR5Delta32). CONCLUSIONS: These data suggest that increased CCL3L1 expression may enhance inflammatory responses and increase the chance of autoimmune disease. Genetic interaction data were consistent with a biologically plausible model; CCR5Delta32 protects against RA and T1D by blocking signalling through the CCR5 pathway, mitigating the pro-inflammatory effects of excess CCL3L1.


Subject(s)
Arthritis, Rheumatoid/genetics , Chemokines, CC/genetics , Gene Dosage , Cohort Studies , Diabetes Mellitus, Type 2/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Receptors, CCR5/genetics , Risk Factors
15.
Cell Mol Life Sci ; 64(7-8): 961-78, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17322987

ABSTRACT

The study of candidate genes over the past three decades has yielded notable successes in common-disease genetics. During this time, however, interpretation of genetic association studies has been hampered by the use of clinical cohorts of inadequate power and insufficient information on genetic variation in candidate genes. The unavailability of highthroughput and low-cost genotyping technologies has also limited the scope of complex-disease genetic studies. More recently, however, the sequencing and characterization of variation within the human genome has revolutionized genetic studies and enabled full genome-wide scans for genes associated with disease. The identification of disease-associated (causative) genes has illuminated disease mechanisms. The translation of this knowledge into direct clinical benefit in diagnosis, prognosis and therapy for an individual's disease still remains a challenge.


Subject(s)
Disease , Genetic Predisposition to Disease , Genetic Techniques , Genome, Human , Humans
16.
Eur J Surg Oncol ; 32(5): 511-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16564154

ABSTRACT

AIMS: This study investigates whether the calcium-sensing receptor (CaR) is commonly expressed in primary breast cancers. The CaR controls secretion of PTHrP in several breast cancer cell lines and PTHrP is known to stimulate osteolysis during metastatic bone resorption. Whether this could explain the propensity of breast cancers to develop bone metastases has not been explored. METHODS: With Ethical Committee approval, immunohistochemistry was performed using a commercially available antiCaR antibody (AffinityBioReagents, Cambridge, UK) on archived histological sections of primary tumours from patients who died with advanced breast cancer. Intensity of CaR expression was assessed by two independent observers on a 6-point scale. RESULTS: One hundred and eight patients with breast cancer were found to have positive bone scans, 42 patients had died. Of the patients with negative bone scans, 23 had liver or lung metastases. Most patients with strongly expressed CaR (score 4-5 on immunohistochemistry) had bone metastases (13/15 patients) compared with 2/23 patients with normal bone scans (p < 0.001, chi(2) test). Other clinical/pathological markers (ER, PR, c-erb B-2, LN status) were not significantly different between patients with CaR-positive or CaR-negative tumours. CONCLUSIONS: CaR expression is common in a selected group of patients with advanced primary breast cancers. A prospective study should investigate if patients with CaR-positive tumours are more likely to develop bone metastases.


Subject(s)
Biomarkers, Tumor/analysis , Bone Neoplasms/secondary , Breast Neoplasms/metabolism , Receptors, Calcium-Sensing/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/secondary , Cause of Death , Female , Forecasting , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lymphatic Metastasis/pathology , Middle Aged , Parathyroid Hormone-Related Protein/metabolism , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Retrospective Studies , Risk Factors
18.
Clin Otolaryngol Allied Sci ; 29(6): 621-7, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15533149

ABSTRACT

The best way to manage small and medium-sized vestibular schwannomas is currently a matter of heated debate. As these tumours are not immediately life-threatening, patients are invariably concerned about how management would affect their quality of life. Until now, no study has compared the three treatment modalities in terms of physical, psychological and social wellbeing. This study is based on a retrospective database analysis and postal questionnaire survey of unilateral vestibular schwannoma patients who had either been managed conservatively, or treated with microsurgery or radiosurgery. The results showed that: quality of life (measured by the Glasgow Benefit Inventory) deteriorated after microsurgery, particularly for small tumours; conservative management did not lead to a change in quality of life, and there was a trend towards poorer quality of life following radiosurgery. The findings suggest that a conservative management approach may be more appropriate for small tumours, and that patients who are due to undergo microsurgery or radiosurgery may benefit from counselling about the potential impact of treatment on quality of life.


Subject(s)
Neuroma, Acoustic/psychology , Neuroma, Acoustic/surgery , Quality of Life , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Microsurgery , Middle Aged , Radiosurgery , Social Support , Surveys and Questionnaires , Time Factors
19.
Neurology ; 63(8): 1403-8, 2004 Oct 26.
Article in English | MEDLINE | ID: mdl-15505156

ABSTRACT

BACKGROUND: fMRI language tasks reliably identify language areas in presurgical epilepsy patients, but activation using single paradigms may disagree with the intracarotid amobarbital test (IAT). OBJECTIVE: To determine whether a panel of fMRI tasks targeting different aspects of language processing increases accuracy in determining hemisphere language dominance. METHODS: Twenty-six patients age 12 to 56 years, predominantly with temporal lobe epilepsy, were studied using whole-brain 1.5 T fMRI (echo planar imaging, blood oxygenation level-dependent) with three task categories using a block design: verbal fluency, reading comprehension, and auditory comprehension. fMRI t maps were visually rated at three thresholds. All patients had assessment of language lateralization by IAT. RESULTS: fMRI showed left dominance in 21 patients, right dominance in 2, and bilateral activation in 2; raters disagreed over a left vs right bilateral rating in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI panel showed consistent findings across raters. Agreement between raters was excellent (partial disagreement in only one patient); the panel of tasks was superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91 to 1.0] vs 0.72 [range 0.60 to 0.86]). CONCLUSIONS: A panel of fMRI language paradigms may be more accurate for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of nondiagnostic findings, improves interrater reliability, and helps confirm language laterality.


Subject(s)
Cerebral Cortex/physiology , Dominance, Cerebral/physiology , Epilepsy/surgery , Language Tests/standards , Magnetic Resonance Imaging/methods , Preoperative Care/methods , Verbal Behavior/physiology , Adolescent , Adult , Brain Mapping/instrumentation , Brain Mapping/methods , Cerebral Cortex/anatomy & histology , Cerebrovascular Circulation/physiology , Child , Epilepsy/physiopathology , Female , Humans , Language , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Speech Perception/physiology , Temporal Lobe/pathology , Temporal Lobe/physiopathology
20.
Clin Otolaryngol Allied Sci ; 26(5): 388-93, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11678946

ABSTRACT

Tinnitus is a common experience with up to one third of the adult population experiencing it at some time in their life. Less than 1% of the adult population have tinnitus of sufficient severity to affect their quality of life seriously (although up to 8% may seek medical advice about it). Much of the severity of tinnitus relates to the individuals' psychological response to the abnormal tinnitus signal. The prevalence of tinnitus increases in association with high frequency hearing loss. There is, unfortunately, no diagnostic test that either confirms the presence of tinnitus or its severity. Currently there is no satisfactory severity grading system. A five-point severity grading scheme is therefore proposed and the entry criteria detailed. The five severity points are: slight, mild, moderate, severe and catastrophic. Categorization as 'severe' or 'catastrophic' should be, by epidemiological definition, very rare. General guidance, theory and evidential support are contained within.


Subject(s)
Severity of Illness Index , Tinnitus/diagnosis , Adult , Aged , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , United Kingdom
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