Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 228; 95% CI: 1.11 to 4.70, p = 0.024) and marginally associated to the risk of POAG in the patients >= 52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p = 0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p = 0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p = 0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p = 0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p = 0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group >= 52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p = 0.002). We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG. (C) 2012 Elsevier B.V. All rights reserved.

Seroprevalence and risk factors associated with Chlamydophila abortus infection in dairy goats in the Northeast of Brazil

Santos C.S.A.B., Piatti R.M., Azevedo S.S., Alves C.J., Higino S.S.S., Silva M.L.C.R., Brasil A.W.L. & Gennari S.M. 2012. Seroprevalence and risk factors associated with Chlamydophila abortus infection in dairy goats in the Northeast of Brazil. Pesquisa Veterinaria Brasileira 32(11):1082-1086. Unidade Academica de Medicina Veterinaria, Centro de Sa de e Tecnologia Rural, Universidade Federal de Campina Grande, Av. Universitaria s/n, Bairro Santa Cecilia, Patos, PB 58700-970, Brazil. E-mail: sergio.azevedo@pq.cnpq.br Few data are available on the prevalence and risk factors of Chlamydophila abortus infection in goats in Brazil. A cross-sectional study was carried out to determine the flock-level prevalence of C. abortus infection in goats from the semiarid region of the Paraiba State, Northeast region of Brazil, as well as to identify risk factors associated with the infection. Flocks were randomly selected and a pre-established number of female goats >= 12 mo old were sampled in each of these flocks. A total of 975 serum samples from 110 flocks were collected, and structured questionnaire focusing on risk factors for C. abortus infection was given to each farmer at the time of blood collection. For the serological diagnosis the complement fixation test (CFT) using C. abortus S26/3 strain as antigen was performed. The flock-level factors for C. abortus prevalence were tested using multivariate logistic regression model. Fifty-five flocks out of 110 presented at least one seropositive animal with an overall prevalence of 50.0% (95%; CI: 40.3%, 59.7%). Ninety-one out of 975 dairy goats examined were seropositive with titers >= 32, resulting in a frequency of 9.3%. Lend buck for breeding (odds ratio = 2.35; 95% CI: 1.04-5.33) and history of abortions (odds ratio = 3.06; 95% CI: 1.37-6.80) were associated with increased flock prevalence.

Multivariate analyses of UV-Vis absorption spectral data from cachaca wood extracts: a model to classify aged Brazilian cachacas according to the wood species used

Multivariate analyses of UV-Vis spectral data from cachaca wood extracts provide a simple and robust model to classify aged Brazilian cachacas according to the wood species used in the maturation barrels. The model is based on inspection of 93 extracts of oak and different Brazilian wood species by a non-aged cachaca used as an extraction solvent. Application of PCA (Principal Components Analysis) and HCA (Hierarchical Cluster Analysis) leads to identification of 6 clusters of cachaca wood extracts (amburana, amendoim, balsamo, castanheira, jatoba, and oak). LDA (Linear Discriminant Analysis) affords classification of 10 different wood species used in the cachaca extracts (amburana, amendoim, balsamo, cabreuva-parda, canela-sassafras, castanheira, jatoba, jequitiba-rosa, louro-canela, and oak) with an accuracy ranging from 80% (amendoim and castanheira) to 100% (balsamo and jequitiba-rosa). The methodology provides a low-cost alternative to methods based on liquid chromatography and mass spectrometry to classify cachacas aged in barrels that are composed of different wood species.

Why Are Women With Cervical Cancer Not Being Diagnosed in Preinvasive Phase? An Analysis of Risk Factors Using a Hierarchical Model

Objective: To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods: This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low-or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals' care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results: The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3-48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3-4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3-13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5-35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1-0.8) for delayed diagnosis. Conclusions: Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology

Abstract Background Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil. Methods This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units. Results Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection. Conclusions Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters ≥ 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

Abstract Background Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. Methods The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach. Results The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. Conclusions The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.

Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss

Aim: To investigate the association of the Periodontal Risk Assessment (PRA) model categories with periodontitis recurrence and tooth loss during supportive periodontal therapy (SPT) and to explore the role of patient compliance. Material and Methods: In a retrospective cohort, PRA was performed for 160 patients after active periodontal therapy (APT) and after 9.5 ± 4.5 years of SPT. The recurrence of periodontitis and tooth loss were analysed according to the patient's risk profile (low, moderate or high) after APT and compliance with SPT. The association of risk factors with tooth loss and recurrence of periodontitis was investigated using logistic regression analysis. Results: In 18.2% of patients with a low-risk profile, in 42.2% of patients with a moderate-risk profile and in 49.2% of patients with a high-risk profile after APT, periodontitis recurred. During SPT, 1.61 ± 2.8 teeth/patient were lost. High-risk profile patients lost significantly more teeth (2.59 ± 3.9) than patients with moderate- (1.02 ± 1.8) or low-risk profiles (1.18 ± 1.9) (Kruskal–Wallis test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal–Wallis test, p=0.0067) more teeth (3.11 ± 4.5) than patients compliant with SPT (1.07 ± 1.6). Conclusions: In multivariate logistic regression analysis, a high-risk patient profile according to the PRA model at the end of APT was associated with recurrence of periodontitis. Another significant factor for recurrence of periodontitis was an SPT duration of more than 10 years.

The SURTAVI model: proposal for a pragmatic risk stratification for patients with severe aortic stenosis

Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis (AS) and a high operative risk. Risk stratification plays a decisive role in the optimal selection of therapeutic strategies for AS patients. The accuracy of contemporary surgical risk algorithms for AS patients has spurred considerable debate especially in the higher risk patient population. Future trials will explore TAVI in patients at intermediate operative risk. During the design of the SURgical replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial, a novel concept of risk stratification was proposed based upon age in combination with a fixed number of predefined risk factors, which are relatively prevalent, easy to capture and with a reasonable impact on operative mortality. Retrospective application of this algorithm to a contemporary academic practice dealing with clinically significant AS patients allocates about one-fourth of these patients as being at intermediate operative risk. Further testing is required for validation of this new paradigm in risk stratification. Finally, the Heart Team, consisting of at least an interventional cardiologist and cardiothoracic surgeon, should have the decisive role in determining whether a patient could be treated with TAVI or SAVR.

Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan. Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads. Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs' effects on patients' annual charges for two types of services, primary care and specialty care, the associations among PCPs' effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: –.40; 95% CI: –.71, –.008) and provided fewer services to patients that they saw (estimated correlation: –.53; 95% CI: –.77, –.21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p < .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73). Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models.

Evaluation of flood risk in response to climate variability

Standard procedures for forecasting flood risk (Bulletin 17B) assume annual maximum flood (AMF) series are stationary, meaning the distribution of flood flows is not significantly affected by climatic trends/cycles, or anthropogenic activities within the watershed. Historical flood events are therefore considered representative of future flood occurrences, and the risk associated with a given flood magnitude is modeled as constant over time. However, in light of increasing evidence to the contrary, this assumption should be reconsidered, especially as the existence of nonstationarity in AMF series can have significant impacts on planning and management of water resources and relevant infrastructure. Research presented in this thesis quantifies the degree of nonstationarity evident in AMF series for unimpaired watersheds throughout the contiguous U.S., identifies meteorological, climatic, and anthropogenic causes of this nonstationarity, and proposes an extension of the Bulletin 17B methodology which yields forecasts of flood risk that reflect climatic influences on flood magnitude. To appropriately forecast flood risk, it is necessary to consider the driving causes of nonstationarity in AMF series. Herein, large-scale climate patterns—including El Niño-Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), North Atlantic Oscillation (NAO), and Atlantic Multidecadal Oscillation (AMO)—are identified as influencing factors on flood magnitude at numerous stations across the U.S. Strong relationships between flood magnitude and associated precipitation series were also observed for the majority of sites analyzed in the Upper Midwest and Northeastern regions of the U.S. Although relationships between flood magnitude and associated temperature series are not apparent, results do indicate that temperature is highly correlated with the timing of flood peaks. Despite consideration of watersheds classified as unimpaired, analyses also suggest that identified change-points in AMF series are due to dam construction, and other types of regulation and diversion. Although not explored herein, trends in AMF series are also likely to be partially explained by changes in land use and land cover over time. Results obtained herein suggest that improved forecasts of flood risk may be obtained using a simple modification of the Bulletin 17B framework, wherein the mean and standard deviation of the log-transformed flows are modeled as functions of climate indices associated with oceanic-atmospheric patterns (e.g. AMO, ENSO, NAO, and PDO) with lead times between 3 and 9 months. Herein, one-year ahead forecasts of the mean and standard deviation, and subsequently flood risk, are obtained by applying site specific multivariate regression models, which reflect the phase and intensity of a given climate pattern, as well as possible impacts of coupling of the climate cycles. These forecasts of flood risk are compared with forecasts derived using the existing Bulletin 17B model; large differences in the one-year ahead forecasts are observed in some locations. The increased knowledge of the inherent structure of AMF series and an improved understanding of physical and/or climatic causes of nonstationarity gained from this research should serve as insight for the formulation of a physical-casual based statistical model, incorporating both climatic variations and human impacts, for flood risk over longer planning horizons (e.g., 10-, 50, 100-years) necessary for water resources design, planning, and management.

Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.

Lesion location predicts transient and extended risk of aspiration after supratentorial ischemic stroke

BACKGROUND AND PURPOSE To assess the association of lesion location and risk of aspiration and to establish predictors of transient versus extended risk of aspiration after supratentorial ischemic stroke. METHODS Atlas-based localization analysis was performed in consecutive patients with MRI-proven first-time acute supratentorial ischemic stroke. Standardized swallowing assessment was carried out within 8±18 hours and 7.8±1.2 days after admission. RESULTS In a prospective, longitudinal analysis, 34 of 94 patients (36%) were classified as having acute risk of aspiration, which was extended (≥7 days) or transient (<7 days) in 17 cases. There were no between-group differences in age, sex, cause of stroke, risk factors, prestroke disability, lesion side, or the degree of age-related white-matter changes. Correcting for stroke volume and National Institutes of Health Stroke Scale with a multiple logistic regression model, significant adjusted odds ratios in favor of acute risk of aspiration were demonstrated for the internal capsule (adjusted odds ratio, 6.2; P<0.002) and the insular cortex (adjusted odds ratio, 4.8; P<0.003). In a multivariate model of extended versus transient risk of aspiration, combined lesions of the frontal operculum and insular cortex was the only significant independent predictor of poor recovery (adjusted odds ratio, 33.8; P<0.008). CONCLUSIONS Lesions of the insular cortex and the internal capsule are significantly associated with acute risk of aspiration after stroke. Combined ischemic infarctions of the frontal operculum and the insular cortex are likely to cause extended risk of aspiration in stroke patients, whereas risk of aspiration tends to be transient in subcortical stroke.

Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer

PURPOSE To explore differential methylation of HAAO, HOXD3, LGALS3, PITX2, RASSF1 and TDRD1 as a molecular tool to predict biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa). METHODS A multiplexed nested methylation-specific PCR was applied to quantify promoter methylation of the selected markers in five cell lines, 42 benign prostatic hyperplasia (BPH) and 71 high-risk PCa tumor samples. Uni- and multivariate Cox regression models were used to assess the importance of the methylation level in predicting BCR. RESULTS A PCa-specific methylation marker HAAO in combination with HOXD3 and a hypomethylation marker TDRD1 distinguished PCa samples (>90 % of tumor cells each) from BPH with a sensitivity of 0.99 and a specificity of 0.95. High methylation of PITX2, HOXD3 and RASSF1, as well as low methylation of TDRD1, appeared to be significantly associated with a higher risk for BCR (HR 3.96, 3.44, 2.80 and 2.85, correspondingly) after correcting for established risk factors. When DNA methylation was treated as a continuous variable, a two-gene model PITX2 × 0.020677 + HOXD3 × 0.0043132 proved to be the best predictor of BCR (HR 4.85) compared with the individual markers. This finding was confirmed in an independent set of 52 high-risk PCa tumor samples (HR 11.89). CONCLUSIONS Differential promoter methylation of HOXD3, PITX2, RASSF1 and TDRD1 emerges as an independent predictor of BCR in high-risk PCa patients. A two-gene continuous DNA methylation model "PITX2 × 0.020677 + HOXD3 × 0.0043132" is a better predictor of BCR compared with individual markers.