Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson`s correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. (C) 2009 Elsevier Ltd. All rights reserved.

Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining

Context: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. Objective: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). Design: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. Results: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). Conclusion: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.

Association Between Polymorphisms in GRIK2 Gene and Obsessive-Compulsive Disorder: A Family-Based Study

Several studies support a genetic influence on obsessive-compulsive disorder (OCD) etiology. The role of glutamate as an important neurotransmitter affecting OCD pathophysiology has been supported by neuroimaging, animal model, medication, and initial candidate gene studies. Genes involved in glutamatergic pathways, such as the glutamate receptor, ionotropic, kainate 2 (GRIK2), have been associated with OCD in previous studies. This study examines GRIK2 as a candidate gene for OCD susceptibility in a family-based approach. Probands had full DSM-IV diagnostic criteria for OCD. Forty-seven OCD probands and their parents were recruited from tertiary care OCD specialty clinics from France and USA. Genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes were analyzed using Haploview and FBAT software. The polymorphism at rs1556995 (P = 0.0027; permuted P-value = 0.03) was significantly associated with the presence of OCD. Also, the two marker haplotype rs1556995/rs1417182, was significantly associated with OCD (P = 0.0019, permuted P-value = 0.01). This study supports previously reported findings of association between proximal GRIK2 SNPs and OCD in a comprehensive evaluation of the gene. Further study with independent samples and larger sample sizes is required.

Autoimmune hemolytic anemia in systemic lupus erythematosus: association with thrombocytopenia

Hematological disturbances are common in systemic lupus erythematous (SLE). Specifically, autoimmune hemolytic anemia (AHA) may manifest in SLE patients at the time of diagnosis or within the first year of the disease. AHA is often associated with thrombocytopenia, lupus nephritis, and central nervous system activity. In this study we investigated these associations in Brazilian patients with SLE. Forty-four consecutive SLE patients who had a history of AHA were age, gender, and disease duration matched with 318 SLE patients without AHA who formed the control group. All patients fulfilled the revised American College of Rheumatology criteria for SLE and were followed-up within our Service. Clinical and laboratorial manifestations were similar in both groups, except for the predominance of leukopenia, thrombocytopenia, and anti-dsDNA on univariate analysis in the AHA group. The multivariate logistic regression model revealed risk only for thrombocytopenia in the AHA group compared to the control group (odds ratio, 2.70; 95% confidence interval, 1.32-5.50). Our results corroborate previous data that AHA in SLE increases the risk of thrombocytopenia in individuals with SLE. This association suggests a common mechanism in AHA and SLE pathophysiologies.

Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

Background: Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). Objective: Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. Methods: 102 FH subjects (36% male, 45 +/- 13 years, LDL-c 280 +/- 54 mg/dL) and 35 controls (40% male, 46 +/- 12 years, LDL-c 103 +/- 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. Results: FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p = 0.0005), stenosis (19% vs. 3%, p = 0.015), segments with plaques (2.05 +/- 2.85 vs. 0.43 +/- 1.33, p = 0.0016) and calcium scores (55 perpendicular to 129 vs. 38 perpendicular to 140, p = 0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR = 2.06, for age change of 10 years, CI95%: 1.38-3.07, p < 0.001) and total cholesterol (OR = 1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p = 0.027). Coronary calcium score was associated with the presence of stenosis (OR = 1.54; CI95%: 1.27-1.86, p < 0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p = 0.014) and inversely with calcified plaques (OR = 0.21, CI95%: 0.05-0.84, p = 0.027). Family history of early CHD was associated with the presence of mixed plaques (OR = 4.90, CI95%: 1.32-18.21, p = 0.018). Conclusions: Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Increased Melanocytic Nevi in Patients with Inherited Ichthyoses: Report of a Previously Undescribed Association

Ichthyosis is a heterogeneous cornification disorder. Melanocytic lesions have not been previously described in association with ichthyosis. Their clinical importance lies in the fact that they may simulate melanoma clinically and dermoscopically, as seen in epidermolysis bullosa. The objective of this study was to evaluate the clinical, dermoscopic, and histopathologic features of nevi and lentigines in 16 patients with autosomal recessive congenital ichthyosis-lamellar ichthyosis and non-bullous ichthyosiform congenital erythroderma. Patients underwent general clinical examination dermoscopy. The more suspicious lesions were excised and to histopathologic examination. Most patients (n = 13) reported no personal or familial history of melanoma or atypical nevi. All of the patients had at least five atypical melanocytic lesions. Ten of the 16 patients had at least one atypical nevus or lentigo. This study suggests that increased atypical melanocytic nevi may be a feature of long-standing congenital ichthyoses. Whether this finding is disease-related or a coincidental observation is difficult to ascertain. As an unequivocal discrimination from malignant melanoma in vivo is not always possible, regular clinical follow-up of patients with ichthyosis and increased or unusual nevi is recommended.

Association Between Integrin Expression and Prognosis in Localized Prostate Cancer

BACKGROUND. Integrins and other adhesion molecules are essential for maintaining the epithelial phenotype. Some studies have reported correlations between abnormalities in their expression and carcinogenesis, but their role in prostate cancer is unclear. Our aim was to study the expression profile of integrins in surgical specimens of prostate cancer and associate their expression patterns with patient outcomes. METHODS. We selected 111 patients with localized prostate cancer who had undergone radical prostatectomy. Of these patients, 60 had no tumor recurrence after a median follow-up of 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two tumor samples per patient. A semiquantitative analysis was employed. We measured the association between the expression of eight integrins and tumor recurrence. RESULTS. Multivariate analysis showed that expression of alpha 3 and alpha 3 beta 1 was related to worse outcome. When alpha 3 expression was strong and alpha 3 beta 1 expression was positive, the odds of recurrence were 3.0- and 2.5-fold higher, respectively. Only 19% and 28% of patients were recurrence-free in a mean period of 123 months of follow up when their tumors showed strong alpha 3 or positive alpha 3 beta 1 immuno-expression, respectively. CONCLUSIONS. We have shown that the expression of integrin alpha 3 beta 1 was independently associated with tumor recurrence after radical prostatectomy, suggesting that this integrin is a potential prognostic marker. Prostate 70: 1189-1195, 2010. (C) 2010 Wiley-Liss, Inc.

The Association Between Physical Activity, Productivity, and Health Care Utilization Among Employees in Brazil

Objective: To document the relationship between physical activity, absenteeism, presenteeism, health care utilization, and morbidity among Brazilian automotive workers. Methods: Eligible employees (N = 620) completed a questionnaire. Univariate correlations, multivariate logistic regression, and Pearson`s product-moment correlation coefficient were used. Results: Work absenteeism was associated with physical activity at work (OPA) (odds ratio, [OR] = 1.63, 95% confidence interval [CI] = 1.31 to 2.02) and leisure physical activity time excluding sport (OR = 0.73, 95% CI = 0.58 to 1.00). Health care utilization was associated with OPA (OR = 1.25, 95% CI = 0.99 to 1.58) and leisure physical activity time excluding sport (OR = 0.76, 95% CI = 0.57 to 1.02). Presenteeism showed an indirect relationship with OPA (r = 0.099, P = 0.014). Referred morbidity was associated with OPA (OR = 1.3, 95% CI = 1.06 to 1.61) and sports during leisure time (OR = 0.67, 95% CI = 0.54 to 0.82). Conclusions: Physical activity components seem to have differential relationships to the studied outcomes. Associations measured indicate negative impacts of OPA on absenteeism, health care utilization, and morbidity, although overall physical activity did not show these relationships.

Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.

Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey

Degenerative aortic valve disease (DAVD), a common finding in the elderly, is associated with an increased risk of death due to cardiovascular causes. Taking advantage of its longitudinal design, this study evaluates the prevalence of DAVD and its temporal associations with long-term exposure to cardiovascular risk factors in the general population. We studied 953 subjects (aged 25-74 years) from a random sample of German residents. Risk factors had been determined at a baseline investigation in 1994/95. At a follow-up investigation, 10 years later, standardized echocardiography determined aortic valve morphology and aortic valve area (AVA) as well as left ventricular geometry and function. At the follow-up study, the overall prevalence of DAVD was 28%. In logistic regression models adjusting for traditional cardiovascular risk factors at baseline age (OR 2.0 [1.7-2.3] per 10 years, P < 0.001), active smoking (OR 1.7 [1.1-2.4], P = 0.009) and elevated total cholesterol levels (OR 1.2 [1.1-1.3] per increase of 20 mg/dL, P < 0.001) were significantly related to DAVD at follow-up. Furthermore, age, baseline status of smoking, and total cholesterol level were significant predictors of a smaller AVA at follow-up study. In contrast, hypertension and obesity had no detectable relationship with long-term changes of aortic valve structure. In the general population we observed a high prevalence of DAVD that is associated with long-term exposure to elevated cholesterol levels and active smoking. These findings strengthen the notion that smoking cessation and cholesterol lowering are promising treatment targets for prevention of DAVD.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Association between personality disorder and violent behavior pattern

Personality disorders are associated with criminality and antisocial and borderline personalities as strong predictors of violence. Nevertheless antisocial patients show more instrumental violence, while borderline patients more emotional violence. We surveilled medical records of a personality disorder facility, searching data of aggression and crimes against property among 11 patients with antisocial personality disorder and 19 borderline personality disorder. We found that there are differences regarding engagement in violence and lawbreaking according to the personality disorder: antisocial patients statistically engage more in crimes against property than the borderline patients, and more in this kind of crime than in aggression, whilst borderline patients show a tendency to engage more in episodes of aggression and physical violence than antisocial patients, and less in crimes against property. We conclude that the distinct personality leads to a distinct pattern of crimes and violence: antisocial patients are c old and get more involved in crimes requiring more detailed planning, whilst borderline patients are impulsive and engage in explosive episodes of physical violence. Further studies on the association among personality disorder, behavior pattern and violence type may be useful for both treatment and criminal profiling. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Association of EGFR c.2073A > T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study

Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C > A and c.-216G > T) and the c.2073A > T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A > T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A > T polymorphism could play a role in future therapeutic approaches to astrocytoma. (Int J Biol Markers 2008; 23: 140-6)

Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy

Context: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue, resulting in severe dyslipidemia and insulin resistance. In most reported cases, BSCL is due to alterations in either seipin, of unknown function, or 1-acylglycerol-3- phosphate acyltransferase-beta (AGPAT2), which catalyzes the formation of phosphatidic acid. Objective: We sought to determine the genetic origin of the unexplained cases of BSCL. We thus sequenced CAV1, encoding caveolin-1, as a candidate gene involved in insulin signaling and lipid homeostasis. CAV1 is a key structural component of plasma membrane caveolae, and Cav1-deficient mice display progressive loss of adipose tissue and insulin resistance. Design: We undertook phenotyping studies and molecular screening of CAV1 in four patients with BSCL with no mutation in the genes encoding either seipin or AGPAT2. Results: A homozygous nonsense mutation (p.Glu38X) was identified in CAV1 in a patient with BSCL born from a consanguineous union. This mutation affects both the alpha-and beta-CAV1 isoforms and ablates CAV1 expression in skin fibroblasts. Detailed magnetic resonance imaging of the proband confirmed near total absence of both sc and visceral adipose tissue, with only vestigial amounts in the dorsal sc regions. In keeping with the lack of adipose tissue, the proband was also severely insulin resistant and dyslipidemic. In addition, the proband had mild hypocalcemia likely due to vitamin D resistance. Conclusions: These findings identify CAV1 as a new BSCL-related gene and support a critical role for caveolins in human adipocyte function.

Candidate-Gene Approach in Posttraumatic Stress Disorder After Urban Violence: Association Analysis of the Genes Encoding Serotonin Transporter, Dopamine Transporter, and BDNF

Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3`UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3`UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.