Publications by authors named "Sidia M Callegari-Jacques"

52 Publications

Cancer Cell Fitness Is Dynamic.

Cancer Res 2021 02 22;81(4):1040-1051. Epub 2020 Dec 22.

Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2488DOI Listing
February 2021

Abdominal Palpation Does Not Modify the Number of Bowel Sounds in Healthy Volunteers and Gastrointestinal Outpatients.

Am J Med Sci 2020 10 2;360(4):378-382. Epub 2020 Jun 2.

Faculdade de Medicina, Universidade de Passo Fundo, Passo Fundo-RS, Brazil. Electronic address:

Background: The effect of abdominal palpation on bowel sounds is controversial. The authors developed an auscultation apparatus to count bowel sounds and determined whether abdominal palpation modifies the number of bowel sounds in healthy volunteers and gastrointestinal outpatients.

Methods: Four medical students developed an auscultation apparatus by attaching a Littmann stethoscope to an electret condenser microphone. The students examined 20 healthy volunteers and 20 gastrointestinal outpatients between March and June 2018. Abdominal auscultation lasting 4 minutes (1-minute each quadrant) was performed before and after abdominal palpation with registration of sound tracings. The software Audacity was used to count the bowel sounds. The effect of palpation on bowel sounds was analyzed using Generalized Estimating Equations.

Results: The volunteers were predominantly young (mean ± SD, 21 ± 2 years) and men (70%), whereas the outpatients were older (60 ± 11 years) and women (80%). The apparatus was able to generate sound tracings with good quality from all participants. In the comparison before/after palpation, the number of bowel sounds did not differ either in volunteers (mean ± SD, 12.6 ± 4.7 and 11.6 ± 3.5; P = 0.482) or in patients (15.6 ± 7.5 and 15.8 ± 7.9; P = 0.714). In the analysis of all participants, the difference before-after palpation was not statistically significant (mean ± SD, 14.1 ± 6.3 and 13.7 ± 6.4, respectively; P = 0.550; mean difference = 0.4; 95% CI -1.2 to 2.0) and did not depend on the group studied.

Conclusions: Using an apparatus devised by medical students, the authors found that abdominal palpation did not modify the number of bowel sounds in healthy volunteers and gastrointestinal outpatients.
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http://dx.doi.org/10.1016/j.amjms.2020.05.041DOI Listing
October 2020

Nuclear morphometric analysis in tissue as an objective tool with potential use to improve melanoma staging.

Melanoma Res 2019 10;29(5):474-482

Department of Pathology, Federal University of Health Sciences of Porto Alegre, Porto Alegre.

Alterations in nuclear size and shape are commonly observed in cancers, and its objective evaluation may provide valuable clinical information about the outcome of the disease. Here, we applied the nuclear morphometric analysis in tissues in hematoxylin and eosin-digitized slides of nevi and melanoma, to objectively contribute to the prognostic evaluation of these tumors. To this, we analyzed the nuclear morphometry of 34 melanomas classified according to the TNM stage. Eight cases of melanocytic nevi were used as non-neoplastic tissues to set the non-neoplastic parameters of nuclear morphology. Our samples were set as G1 (control, nevi), G2 (T1T2N0M0), G3 (T3T4N0M0), G4 (T1T2N1M1), and G5 (T3T4N1M1). Image-Pro Plus 6.0 software was used to acquire measurements related to nuclear size (variable: Area) and shape (variables: Aspect, AreaBox, Roundness, and RadiusRatio, which were used to generate the Nuclear Irregularity Index). From these primary variables, a set of secondary variables were generated. All the seven primary and secondary variables related to the nuclear area were different among groups (Pillai's trace P<0.001), whereas Nuclear Irregularity Index, which is the variable related to nuclear shape, did not differ among groups. The secondary variable 'Average Area of Large Nuclei' was able to differ all pairwise comparisons, including thin nonmetastatic from thin metastatic tumors. In conclusion, the objective quantification of nuclear area in hematoxylin and eosin slides may provide objective information about the risk stratification of these tumors and has the potential to be used as an additional method in clinical decision making.
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http://dx.doi.org/10.1097/CMR.0000000000000594DOI Listing
October 2019

The somatic mobilization of transposable element mariner-Mos1 during the Drosophila lifespan and its biological consequences.

Gene 2018 Dec 30;679:65-72. Epub 2018 Aug 30.

Programa de Pós-Graduação em Biodiversidade Animal, Universidade Federal de Santa Maria, Santa Maria, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Dep. Biochemistry and Molecular Biology -Universidade Federal de Santa Maria, Av. Roraima 1000, 97105900 Santa Maria, Brazil. Electronic address:

Transposable elements (TEs) are mobile DNA sequences on genomes. Some elements are able to transpose in somatic cells, a process known as somatic transposition (ST), which has been associated with detrimental biological effects. The mariner-Mos1 element of Drosophila promotes transposition in somatic and germline cells and is an excellent model for studies related to the biological consequence of somatic excision (SE). In this work, we used temperature stress to induce increasing transposition of mariner-Mos1 during different stages of the development of D. simulans, aiming to quantify SE during lifespan. Furthermore, strains of D. melanogaster exhibiting differential expression of mariner-Mos1 were employed for estimating some biological consequences of mariner mobilization. It is shown that SE of mariner-Mos1 was not constant during development; the larval phase had the highest rates while the pupal stage exhibited lower rates, and in the embryonic stage, no difference was detected. SE can be detrimental, as suggested by correlation in SE level and reduction in behavioral activities and embryonic viability. This study showed that mariner-Mos1 SE accumulates during the Drosophila life cycle, and can be involved in detrimental effects.
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http://dx.doi.org/10.1016/j.gene.2018.08.079DOI Listing
December 2018

Acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia.

Logoped Phoniatr Vocol 2018 Dec 15;43(4):169-174. Epub 2018 Aug 15.

f Pediatric Gastroenterology Unit , HCPA, UFRGS , Porto Alegre , Brazil.

Objetive: The aim of this study was to characterize the acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia (OPD).

Method: Thirty-two children with OPD were examined with combined digital cervical auscultation (DCA) and videofluoroscopic swallow study (VFSS). Power spectral density (PSD, in 1/√Hz) of the acoustic signal from a sequential series of five liquid swallows was used for comparisons between children who silently aspirated and children who did not aspirate on VFSS. Fourteen children were excluded due to either DCA/VFSS artifact or non-silent aspiration (cough, choking).

Results: The remaining 18 participants (median age 6 years, range 2-12.8) were classified based on VFSS as aspirators (n = 8) and non-aspirators (n = 10). The PSD curve of aspirators presented an ascending pattern (1st vs. 5th deglutition: 695.2 vs. 4421.9 1/√Hz), while the curve of non-aspirators was flat (1st vs. 5th deglutition: 509 vs. 463.4 1/√Hz), with marked differences being observed from the 3rd measure onwards (p < .001). In this study, DCA was able to identify silent tracheal aspiration in children with OPD.

Conclusion: This non-invasive technique identified aspiration by an increase in the PSD curve in aspiration sounds.
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http://dx.doi.org/10.1080/14015439.2018.1487993DOI Listing
December 2018

Cytological and genome size data analyzed in a phylogenetic frame: Evolutionary implications concerning Sisyrinchium taxa (Iridaceae: Iridoideae).

Genet Mol Biol 2018 1;41(1 suppl 1):288-307. Epub 2018 Mar 1.

Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Sisyrinchium is the largest genus of Iridaceae in the Americas and has the greatest amount of cytological data available. This study aimed at investigating how genomes evolved in this genus. Chromosome number, genome size and altitude from species of sect. Viperella were analyzed in a phylogenetic context. Meiotic and pollen analyses were performed to assess reproductive success of natural populations, especially from those polyploid taxa. Character optimizations revealed that the common ancestor of sect. Viperella was probably diploid (2n = 2x =18) with two subsequent polyplodization events. Total DNA content (2C) varied considerably across the phylogeny with larger genomes detected mainly in polyploid species. Altitude also varied across the phylogeny, however no significant relationship was found between DNA content changes and altitude in our data set. All taxa presented regular meiosis and pollen viability (> 87%), except for S. sp. nov. aff. alatum (22.70%), suggesting a recent hybrid origin. Chromosome number is mostly constant within this section and polyploidy is the only source of modification. Although 2C varied considerably among the 20 taxa investigated, the diversity observed cannot be attributed only to polyploidy events because large variations of DNA content were also observed among diploids.
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http://dx.doi.org/10.1590/1678-4685-GMB-2017-0077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913718PMC
March 2018

Juice Test for Identification of Nonerosive Reflux Disease in Heartburn Patients.

J Neurogastroenterol Motil 2018 Apr;24(2):233-240

Faculdade de Medicina, Universidade de Passo Fundo (UPF), Passo Fundo-RS, Brazil.

Background/aims: Evaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients.

Methods: Multiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol∙L⁻¹∙sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy.

Results: Delta5 cutoff in healthy subjects was 251 mmol·L⁻¹∙sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213-472] vs 165 [105-225]; < 0.01) and erosive disease (310 [169-625] vs 165 [105-225]; < 0.01). An elevated Delta5 (> 251 mmol∙L⁻¹∙sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%.

Conclusions: A juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.
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http://dx.doi.org/10.5056/jnm17077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885722PMC
April 2018

and genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect.

J Psychiatry Neurosci 2016 10;41(6):405-412

From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase () and of the dopamine transporter () genes on ADHD symptoms in the general population.

Methods: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes.

Results: Linear regression analyses demonstrated that the increasing number of 158Val and 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, = 2.189, = 0.029, = 0.012, and β coefficient = 0.064, = 2.832, = 0.005, = 0.008, respectively). The presence of both 158Val and 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ = 4.561, = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls.

Limitations: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated.

Conclusion: This study demonstrates a role for and genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on and gene expression.
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http://dx.doi.org/10.1503/jpn.150270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082511PMC
October 2016

Influence of genetic, biological and pharmacological factors on levodopa dose in Parkinson's disease.

Pharmacogenomics 2016 Apr 29;17(5):481-8. Epub 2016 Mar 29.

Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Aim: Levodopa is first-line treatment of Parkinson's disease motor symptoms but, dose response is highly variable. Therefore, the aim of this study was to determine how much levodopa dose could be explained by biological, pharmacological and genetic factors.

Patients & Methods: A total of 224 Parkinson's disease patients were genotyped for SV2C and SLC6A3 polymorphisms by allelic discrimination assays. Comedication, demographic and clinical data were also assessed.

Results: All variables with p < 0.20 were included in a multiple regression analysis for dose prediction. The final model explained 23% of dose variation (F = 11.54; p < 0.000001).

Conclusion: Although a good prediction model was obtained, it still needs to be tested in an independent sample to be validated.
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http://dx.doi.org/10.2217/pgs.15.183DOI Listing
April 2016

Gastro-oesophageal reflux disease and dental erosions in adults: influence of acidified food intake and impact on quality of life.

Eur J Gastroenterol Hepatol 2016 Jul;28(7):797-801

aPost-Graduation Program in Dentistry, Dental School bMedical School, University of Passo Fundo, Passo Fundo cDepartment of Statistics, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Background And Aim: Gastro-oesophageal reflux disease (GORD) and dental erosions (DE) have an established association. We assessed whether GORD is associated with DE controlling for acidified food intake and their relationships with quality of life (QOL).

Methods: In this cross-sectional study, 419 adult patients who sought dentistry consultation were considered eligible. Patients responded to questionnaires for GORD symptoms, acidified food ingestion and World Health Organization quality of life (WHOQOL Bref), followed by an oral examination, in which DE were characterized according to the Smith & Knight criteria.

Results: A total of 417 patients were included (43.8±13.7 years; 68.8% women). There were 143 patients with GORD (34.3%) and 274 controls without GORD. The prevalence of DE was higher in GORD patients compared with the controls (25.9 vs. 17.2%; P=0.041). GORD was associated with DE after adjusting for acidified food intake (P=0.035), with a prevalence ratio of 1.52 (0.95 confidence interval 1.03-2.22). The WHOQOL Bref score was significantly lower in the presence of GORD [median 17.2 (GORD-DE-) vs. 15.4 (GORD+DE+); P<0.01], irrespective of DE.

Conclusion: In adults examined in a referential dentistry centre in South America, DE were prevalent and significantly associated with GORD. This association was independent of the intake of acidified food in our study. Impairment in QOL was observed in GORD patients irrespective of the presence of DE.
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http://dx.doi.org/10.1097/MEG.0000000000000622DOI Listing
July 2016

Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment.

Neurosci Lett 2016 Feb 21;615:88-91. Epub 2016 Jan 21.

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Brazil. Electronic address:

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Besides characteristic PD motor features, the disease has important non-motor characteristics such as cognitive impairment. The role of genetic factors in cognitive impairment associated with PD is still unclear. In this study, we examined whether BDNF Val66Met was associated with impaired cognition in Parkinson's disease. One hundred and seventy five patients with a clinical diagnosis of Parkinson's disease were included. Global cognitive abilities of the patients were measured by the Mini-Mental State Examination (MMSE). Poisson Regression models were used to test for association between 66Met carriers and cognitive impairment controlling for covariates. Carriers of at least one BDNF 66Met allele presented a higher prevalence of cognitive impairment (p=0.005 RR=1.45 IC=95% [1.1-1.8]). These results suggest a role for BDNF Val66Met polymorphism on cognitive impairment in PD.
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http://dx.doi.org/10.1016/j.neulet.2016.01.030DOI Listing
February 2016

High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs).

Genet Mol Biol 2015 Jul-Sep;38(3):324-31. Epub 2015 Aug 21.

Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow.
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http://dx.doi.org/10.1590/S1415-475738320140260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612595PMC
October 2015

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment.

J Psychiatr Res 2015 Sep 20;68:83-90. Epub 2015 Jun 20.

Developmental Cognitive Neuroscience Research Group (GNCD), Biomedical Research Institute (IPB), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil.

The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (NR3C2 and NR3C1, respectively). One hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. Childhood adversities were assessed using the Childhood Trauma Questionnaire (CTQ), and withdrawal symptoms were assessed using the Cocaine Selective Severity Assessment (CSSA) scale. Conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. We found an interaction between the rs5522-Val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (Odds ratio = 4.0, P = 0.001). Moreover, a NR3C2-NR3C1 interaction (P = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. In the post hoc analysis, concomitant carriers of the NR3C2 rs5522-Val and NR3C1 rs6198-G alleles showed lower overall severity scores when compared to other genotype groups (P-values ≤ 0.035). This gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in cocaine addiction. Additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between NR3C2 and NR3C1 genes.
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http://dx.doi.org/10.1016/j.jpsychires.2015.06.008DOI Listing
September 2015

Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients?

Pharmacogenomics 2015 15;16(6):573-82. Epub 2015 Apr 15.

Departmento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa postal 15053, Porto Alegre, RS, 91501-970, Brazil.

Aim: Levodopa is first line treatment of Parkinson's disease (PD). However, its use is associated with the presence of motor fluctuations and dyskinesias. In recent years, adenosine A2A receptor (A2AR) is rising as a therapeutic target for PD. The aim of the present study was to investigate whether ADORA2A is associated with levodopa adverse effects.

Patients & Methods: Two hundred and eight PD patients on levodopa therapy were investigated. rs2298383 and rs3761422 at the ADORA2A gene were genotyped by allelic discrimination assays.

Results: A trend for association was observed for both polymorphism and diplotypes with dyskinesia.

Conclusion: The present results should be considered as positive preliminary evidence. Further studies are needed to determine the association between ADORA2A and dyskinesia. Original submitted 3 December 2014; Revision submitted 13 February 2015.
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http://dx.doi.org/10.2217/pgs.15.23DOI Listing
February 2016

The Impact of Gastric Bypass on Gastroesophageal Reflux Disease in Morbidly Obese Patients.

Ann Surg 2016 Jan;263(1):110-6

*Department of Surgery, GASTROBESE, Passo Fundo, RS, Brazil †Hospital Universitário São Vicente de Paulo, Passo Fundo, RS, Brazil ‡Post-Graduate Program in Surgery, School of Medicine, UFRGS, Porto Alegre, RS, Brazil §School of Medicine, Hospital de Clinicas de Porto Alegre, UFRGS, Porto Alegre, RS, Brazil ¶Department of Statistics, UFRGS, Porto Alegre, RS, Brazil ||School of Medicine, Universidade de Passo Fundo, Passo Fundo, RS, Brazil.

Objective: To assess the impact of Roux-en-Y gastric bypass (GBP) on gastroesophageal reflux disease (GERD) in morbidly obese patients.

Background: Recently, authors have reported that early results of GBP can control GERD. However, longer follow-ups based on objective parameters for GERD are missing.

Methods: Fifty-three patients [15 men (28%), 39 years old (range, 18-59), body mass index = 46 ± 7.7 kg/m2] were consecutively evaluated for GERD irrespectively of related symptoms, before the operation (E1) and at 6 (E2) and 39 ± 7 months postoperatively (E3). The end points were (1) esophageal syndromes based on the Montreal Consensus and (2) an esophageal acid exposure assessment.

Results: Body mass index dropped from 46 ± 7.7 kg/m2 at E1 to 30 ± 5.2 kg/m2 at E3. Typical reflux syndrome displayed a significant decrease from 31 (58%) at E1 to 8 (15%) at E2 and 5 (9%) at E3. Statistically significant differences occurred between E1 and both postoperative evaluations (P < 0.001). Reflux esophagitis was detected in 24 (45%), 17 (32%), and 10 patients (19%) at E1, E2, and E3, respectively (P = 0.002). The incidence of GERD decreased in 34 (64%) and 21 (40%) patients at E1 and E2, respectively, and then in 12 (23%) patients at E3. DeMeester scores reduced from 28.6 (E1) to 9.4 (E2) and 1.2 (E3) (P < 0.001).

Conclusions: For most morbidly obese patients, in addition to causing significant weight loss, GBP reduces GERD symptoms, improves reflux esophagitis, and decreases esophageal acid exposure for longer than 3 years.
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http://dx.doi.org/10.1097/SLA.0000000000001139DOI Listing
January 2016

The lactase persistence genotype is a protective factor for the metabolic syndrome.

Genet Mol Biol 2014 Oct 21;37(4):611-5. Epub 2014 Oct 21.

Departamento de Genética , Universidade Federal do Rio Grande do Sul , Porto Alegre, RS , Brazil .

The Metabolic Syndrome (MetS) is defined as a pattern of metabolic disturbances, which include central obesity, insulin resistance and hyperglycemia, dyslipidemia, and hypertension. Milk has been promoted as a healthy beverage that can improve the management of MetS. Most human adults, however, down-regulate the production of intestinal lactase after weaning. Lactase encoded by the LCT gene is necessary for lactose digestion. The -13910C > T SNP (rs4988235) is responsible for the lactase persistence phenotype in European populations. We herein investigated whether the lactase persistence genotype is also associated with the MetS in subjects from a Brazilian population of European descent. This study consisted of 334 individuals (average age of 41 years) genotyped by PCR-based methods for the -13910C > T SNP. Clinical data were assessed and the genotypes were tested for their independent contribution to the MetS using chi-square tests and multiple logistic regression analysis. Univariate analyses showed that hypertension and MetS prevalence were higher in individuals with the lactase non-persistence genotype than in lactase persistence subjects. Furthermore, lactase persistence was associated with a lower risk for MetS (OR = 0.467; 95% CI 0.264-0.824; p = 0.009). These results suggest that LCT genotypes can be a valuable tool for the management of MetS treatment.
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http://dx.doi.org/10.1590/S1415-47572014005000012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261958PMC
October 2014

MR and GR functional SNPs may modulate tobacco smoking susceptibility.

J Neural Transm (Vienna) 2013 Oct 31;120(10):1499-505. Epub 2013 Mar 31.

Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves - 15053, Porto Alegre, RS, 91501-970, Brazil.

A number of studies have demonstrated that stress is involved in all aspects of smoking behavior, including initiation, maintenance and relapse. The mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis. As nicotine increases the activation of the HPA axis, we wondered if functional SNPs (single nucleotide polymorphisms) in MR and GR coding genes (NR3C2 rs5522 and NR3C1 rs6198, respectively) may be involved in smoking susceptibility. The sample included 627 volunteers, of which 514 were never-smokers and 113 lifetime smokers. We report an interaction effect between rs5522 and rs6198 SNPs. The odds ratio (OR) for the presence of the NR3C2 rs5522 Val allele in NR3C1 rs6198 G carriers was 0.18 (P = 0.007), while in rs6198 G noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total score of the Fagerström Test for Nicotine Dependence (P = 0.007). These findings are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and smoking behavior and provide a first partial replication for a nominally significant GWAS finding between NR3C2 and tobacco smoking.
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http://dx.doi.org/10.1007/s00702-013-1012-2DOI Listing
October 2013

Polymorphisms in the dopamine transporter gene are associated with visual hallucinations and levodopa equivalent dose in Brazilians with Parkinson's disease.

Int J Neuropsychopharmacol 2013 Jul 30;16(6):1251-1258. Epub 2013 Jan 30.

Departmento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

The requirement for dopaminergic drugs in Parkinson's disease (PD) is highly variable. Visual hallucinations are a frequent and serious complication of chronic levodopa therapy. Polymorphisms in the DAT1 gene might affect the reuptake of dopamine in the synaptic cleft, but the influence of this variability on adverse effects or levodopa equivalent dose on PD patients is still poorly investigated. Therefore, the aim of the present study was to investigate DAT1 gene polymorphisms on levodopa equivalent dose and visual hallucination occurrence in PD patients. Altogether, 196 PD patients in treatment with at least 200 mg levodopa equivalent dose for at least 1 yr were included. These patients were genotyped for the -839 C > T and 3' VNTR DAT1 polymorphisms by PCR-based methodologies. Visual hallucinations occurred in 25.5% of the sample. After controlling for confounders, the dopamine transporter (DAT) -839 C allele was associated with visual hallucinations (prevalence ratio 2.5, 95% confidence intervals 1.13-5.5, p = 0.02). Levodopa equivalent dose was lower in carriers of the nine repeat allele of the DAT 3'UTR VNTR (741.2 ± 355.0 vs. 843.4 ± 445.7), explaining 21% of dose variability (p = 0.01). Our results support an effect of DAT1 polymorphisms in adverse effects of anti-Parkinsonian drugs and in levodopa equivalent dose usage.
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http://dx.doi.org/10.1017/S1461145712001666DOI Listing
July 2013

Gastric yield pressure and gastric yield volume to assess anti-reflux barrier in a porcine model.

J Invest Surg 2013 Apr 28;26(2):80-4. Epub 2012 Dec 28.

Programa de Pós-graduação Ciências em Gastroenterologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul UFRGS, Porto Alegre, Brazil.

Anti-reflux barrier (ARB) resistance may be useful to test new treatments for gastroesophageal reflux (GER). The ARB has been estimated by increasing gastric yield pressure (GYP) and gastric yield volume (GYV) in animal models but has not been validated. This study aimed to develop an experimental model suitable for assessing the ARB resistance to increasing intragastric pressure and volume and its reproducibility in a seven-day interval. Ten two-month-old female Large-White swine were studied. Intragastric pressure and volume were recorded using a digital system connected to a Foley catheter inserted through gastrostomy into the stomach. GYP and GYV were defined as the gastric pressure and volume able to yield gastric contents into the esophagus detected by esophageal pH. A sudden pH drop below 3 sustained during 5 min was considered diagnostic for gastric yield. Animals were studied again after seven days. On days 0 and 7, there were no significant differences for GYP (mean ± SD = 7.66 ± 3.02 mmHg vs. 7.07 ± 3.54 mmHg, p = .686) and GYV (636.70 ± 216.74 ml vs. 608.30 ± 276.66 ml; p = .299), respectively. Concordance correlation coefficient (ρc) was significant for GYP (ρc = 0.634, 95% CI = 0.141-0.829, p = .006), but not for GYV (ρc = 0.291, 95% CI = -0.118 to 0.774, p = .196). This study demonstrated an experimental model, assessing the ARB resistance. GYP seems to be a more reliable parameter than GYV for assessment of ARB resistance.
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http://dx.doi.org/10.3109/08941939.2012.695429DOI Listing
April 2013

IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil.

Malar J 2012 Dec 7;11:409. Epub 2012 Dec 7.

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Background: Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood.

Methods: The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test.

Results: The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively).

Conclusion: Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.
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http://dx.doi.org/10.1186/1475-2875-11-409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537609PMC
December 2012

DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in Parkinson's disease patients.

Pharmacogenomics 2012 Nov;13(15):1701-10

Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.

Aim: Dyskinesia and motor fluctuation are frequent and serious complications of chronic levodopa therapy in patients with Parkinson's disease. Since genetic factors could play a role in determining the occurrence of these problems, the aim of the present study was to investigate whether possible functional polymorphisms among DRD2 and ANKK1 genes are associated with the risk of developing dyskinesia and motor fluctuations in Parkinson's disease patients.

Patients & Methods: One hundred and ninety nine patients in treatment with levodopa were genotyped for the -141CIns/Del, rs2283265, rs1076560, C957T, TaqIA and rs2734849 polymorphisms at the DRD2/ANKK1 gene region.

Results: Carriers of the TTCTA haplotype showed an increased risk for the presence of dyskinesia (p = 0.007; 1.538 [95% CI: 1.126-2.101]).

Conclusion: Our data suggest an influence of the DRD2/ANKK1 gene region on levodopa-induced dyskinesia.
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http://dx.doi.org/10.2217/pgs.12.149DOI Listing
November 2012

Stability or variation? Patterns of lactase gene and its enhancer region distributions in Brazilian Amerindians.

Am J Phys Anthropol 2012 Mar 23;147(3):427-32. Epub 2012 Jan 23.

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970, Porto Alegre, RS, Brazil.

Lactase persistence (LP) is the phenotypic trait in which lactase secretion is maintained during adulthood. LP is due to mutations in the LCT enhancer region, located 14-kb upstream of the gene. In Europeans, the -13910*T allele is associated with LP. In Africans this allele is rare while other mutations in this same region were related to LP. The LCT is highly polymorphic in human populations, but so far Brazilian Amerindians had not been investigated for these polymorphisms or for the presence of LP mutations. We describe the genetic diversity of the LCT region and the presence of LP enhancer mutations in four native Brazilian populations (Guarani-Kaiowá, Guarani-Ñandeva, Kaingang, and Xavante). Twelve polymorphisms were genotyped by PCR-based methods. The -13910*T allele varied from 0.5% in the Xavante to 7.6% in the Guarani-Ñandeva. These frequencies probably derive from European sources and they correlate with non-native admixture proportions previously estimated for these groups. But since admixture is virtually absent in the Xavante, we suggest that the presence of the LP allele could have been determined by a de novo mutation. No other mutations in the -14 kb enhancer region were found. The LCT was highly polymorphic in the present sample showing 15 haplotypes with a heterogeneous distribution among the four Amerindian populations. This diversity could be due to drift, as indicated by the neutrality test performed.
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http://dx.doi.org/10.1002/ajpa.22010DOI Listing
March 2012

Prevalence of common α-thalassemia determinants in south Brazil: Importance for the diagnosis of microcytic anemia.

Genet Mol Biol 2010 Oct 1;33(4):641-5. Epub 2010 Dec 1.

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.

Alpha thalassemia has not been systematically investigated in Brazil. In this study, 493 unrelated individuals from the southernmost Brazilian state of Rio Grande do Sul were screened for deletional forms of α-thalassemia. One hundred and one individuals had microcytic anemia (MCV < 80 fL) and a normal hemoglobin pattern (Hb A (2) < 3.5% and Hb F < 1%). The subjects were screened for - α(3.7) , - α(4.2) , - α(20.5) , - (SEA) and - (MED) deletions but only the - α(3.7) allele was detected. The - α(3.7) allele frequency in Brazilians of European and African ancestry was 0.02 and 0.12, respectively, whereas in individuals with microcytosis the frequency was 0.20. The prevalence of α-thalassemia was significantly higher in individuals with microcytosis than in healthy individuals (p = 0.001), regardless of their ethnic origin. There were also significant differences in the hematological parameters of individuals with - α(3.7) / αα, - α(3.7) /- α(3.7) and β-thalassemia trait compared to healthy subjects. These data suggest that α-thalassemia is an important cause of microcytosis and mild anemia in Brazilians.
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http://dx.doi.org/10.1590/S1415-47572010005000086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036136PMC
October 2010

Catechol-O-methyltransferase valine158methionine polymorphism moderates methylphenidate effects on oppositional symptoms in boys with attention-deficit/hyperactivity disorder.

Biol Psychiatry 2011 Aug 6;70(3):216-21. Epub 2011 May 6.

Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: The catechol-O-methyltransferase enzyme plays a key role in the function of prefrontal cortex, accounting for most of the degradation of dopamine. Previous studies have documented the improvement of oppositional symptoms in attention-deficit/hyperactivity disorder (ADHD) patients with methylphenidate (MPH) treatment. However, the effect of the COMT gene in the response to MPH on oppositional symptoms has not been investigated.

Methods: A total of 251 children with ADHD fulfilled inclusion criteria to participate in the study. Dosages of short-acting MPH were augmented until no further clinical improvement was detected or until there were significant adverse events (MPH dose always > .3 mg/kg/day). The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV). The scale was applied by child psychiatrists blinded to genotype at baseline and in the first and third months. The COMT valine158methionine polymorphism was genotyped by polymerase chain reaction based methods.

Results: We detected significant improvement in SNAP-IV oppositional scores from baseline to the first and three months of treatment [n = 112; F(2,231) = 5.35, p = .005]. A significant effect of the presence of methionine allele in oppositional defiant disorder scores during treatment [F(1,148) = 5.02, p = .027] and a significant interaction between the methionine allele and treatment over time for the SNAP-IV oppositional scores during this period of treatment [F(2,229) = 6.40, p = .002] were both observed.

Conclusions: These results suggest an effect of the COMT genotype on the trajectory of oppositional defiant disorder symptoms improvement with MPH treatment in boys with ADHD.
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http://dx.doi.org/10.1016/j.biopsych.2011.03.025DOI Listing
August 2011

Autosome STRs in native South America-Testing models of association with geography and language.

Am J Phys Anthropol 2011 Jul 25;145(3):371-81. Epub 2011 Apr 25.

Departamento de Genética, Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Information on one Ecuadorian and three Peruvian Amerindian populations for 11 autosomal short tandem repeat (STR) loci is presented and incorporated in analyses that includes 26 other Native groups spread all over South America. Although in comparison with other studies we used a reduced number of markers, the number of populations included in our analyses is currently unmatched by any genome-wide dataset. The genetic polymorphisms indicate a clear division of the populations into three broad geographical areas: Andes, Amazonia, and the Southeast, which includes the Chaco and southern Brazil. The data also show good agreement with proposed hypotheses of splitting and dispersion of major language groups over the last 3,000 years. Therefore, relevant aspects of Native American history can be traced using as few as 11 STR autosomal markers coupled with a broad geographic distribution of sampled populations.
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http://dx.doi.org/10.1002/ajpa.21505DOI Listing
July 2011

Obese patients have stronger peristalsis and increased acid exposure in the esophagus.

Dig Dis Sci 2011 May 24;56(5):1420-6. Epub 2010 Oct 24.

Faculdade de Medicina, Universidade de Passo Fundo, Rua Teixeira Soares, 817, Passo Fundo-RS, 99010-080, Brazil.

Background: Obesity is a risk factor for GERD and a potential modulator of esophageal motility.

Aim: To assess whether obese patients differ from non-obese patients in terms of esophageal motility and reflux.

Methods: Patients (n = 332) were categorized in GERD and controls after clinical assessment, esophageal manometry, and pH monitoring. Non-obese (BMI 16-29.9) and obese (BMI 30-68) were compared in regard of distal esophageal amplitude (DEA), LES pressure (LESP), manometric diagnosis, and esophageal acid exposure (EAE).

Results: Obese showed higher DEA in both controls (122 ± 53 vs. 97 ± 36 mmHg, p = 0.041) and GERD patients (109 ± 38 vs. 94 ± 46 mmHg, p < 0.001), higher LESP in GERD patients (20.5 ± 10.6 vs. 18.2 ± 10.6 mmHg, p = 0.049), higher frequency of nutcracker esophagus in controls (30 vs. 0%, p = 0.001), lower frequency of ineffective motility in GERD patients (6 vs. 20%, p = 0.001), and higher EAE in both controls [total EAE: 1.6% (0.7-5.1) vs. 0.9% (0.2-2.4), p = 0.027] and GERD patients [upright EAE: 6.5% (3.8-11.1) vs. 5.2% (1.5-10.6), p = 0.048]. Multiple linear regression showed that BMI was associated either with EAE (p < 0.001), DEA (p = 0.006), or LESP (in men, p = 0.007).

Conclusions: Obese patients differed from non-obese in terms of esophageal motility and reflux, regardless of the presence of GERD. Obese patients showed stronger peristalsis and increased acid exposure in the esophagus.
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http://dx.doi.org/10.1007/s10620-010-1454-4DOI Listing
May 2011

Dopamine receptor D4 allele distribution in Amerindians: a reflection of past behavior differences?

Am J Phys Anthropol 2010 Nov;143(3):458-64

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.

The DRD4 variable number of tandem repeats (VNTR) allele distribution of 172 Guarani (Kaiowá and Ñandeva subgroups) and Kaingang Brazilian Amerindians is reported. These results are integrated with those previously obtained for this ethnic group. Allele frequencies for the three populations are within the interval observed for 15 other Native American populations and show intermediate values between those observed in Amazonia and Patagonia. Significant differences in allele distribution between recent past hunter-gatherer and agriculturalist populations are observed, with an increase of the 7R allele among hunter-gatherers (P < 0.001). Analysis of molecular variance (AMOVA) and pairwise F(ST) data suggest three distinct sectors for the genetic landscape of Native South America: Andes, Center/Southeast region, and Amazonia. Common traits among hunter-gatherers such as novelty-seeking temperament, hyperactivity, and impulsivity could have been important and advantageous in new environments during America's prehistoric colonization.
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http://dx.doi.org/10.1002/ajpa.21358DOI Listing
November 2010

The role of gastro-oesophageal pressure gradient and sliding hiatal hernia on pathological gastro-oesophageal reflux in severely obese patients.

Eur J Gastroenterol Hepatol 2010 Apr;22(4):404-11

Department of Clinical Research, GASTROBESE, Passo Fundo-RS, Brazil.

Background And Aims: The relationship between gastro-oesophageal pressure gradient (GOPG), sliding hiatal hernia (SHH) and gastro-oesophageal reflux disease (GORD) is under investigation. We assessed whether GOPG and SHH are predictors of pathological reflux in severely obese patients.

Methods: Ninety-four consecutive patients were prospectively studied with oesophageal manometry, 24-h pH monitoring, upper gastrointestinal endoscopy and barium swallow X-ray. Inspiratory and expiratory GOPGs were measured at manometry testing, whereas SHH was characterized by X-ray. Patients were classified as having physiological or pathological reflux depending on pH monitoring. Patients with oesophagitis but normal pH testing were excluded.

Results: Eighty-nine patients composed the study sample (25 men, 38.3+/-11.1 years; BMI 45+/-6.9 kg/m). Sixty-two patients (70%) had pathological reflux, whereas 27 patients (30%) had physiological reflux. Pathological reflux was predicted either by inspiratory GOPG [prevalence ratio (PR) =1.05; 95% confidence interval (CI): 1.03-1.08; P<0.001] or by expiratory GOPG (PR=1.07; 95% CI: 1.03-1.11; P=0.001). Accordingly, an increment of 1 mmHg in inspiratory and expiratory GOPGs raises the risk of pathological reflux in 5 and 7%, respectively. Pathological reflux was also predicted by SHH (PR: 1.54, 95% CI: 1.19-2.00; P=0.001), which increases the risk of abnormal reflux in 54%.

Conclusion: In severely obese patients, either inspiratory GOPG, expiratory GOPG or SHH are predictors of pathological reflux. These findings give pathophysiological support to the high prevalence of GORD in this population.
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http://dx.doi.org/10.1097/MEG.0b013e328332f7b8DOI Listing
April 2010

The impact of gastric bypass on gastroesophageal reflux disease in patients with morbid obesity: a prospective study based on the Montreal Consensus.

Ann Surg 2010 Feb;251(2):244-8

Department of Surgery, Gastrobese, Passo Fundo, RS, Brazil.

Objectives: To assess the impact of gastric bypass (GBP) on gastroesophageal reflux disease (GERD) based on Montreal Consensus.

Methods: In this study, 86 patients (25 men; aging 38 +/- 12 years; body mass index 45 [35-68 kg/m2]) were investigated for GERD before GBP and 6 months later. Esophageal and extraesophageal syndromes were assessed based on Montreal Consensus. Esophageal acid exposure and gastric pouch acidity were also evaluated.

Results: Overall prevalence of GERD was 64% before GBP and 33% after GBP (P < 0.0001). Typical reflux syndrome (TRS) was present in 47 patients (55%) preoperatively and disappeared in 39 of them (79%) post-GBP. Out of 39 patients with no symptoms, 4 (10%) developed TRS postoperatively (P < 0.0001). The chief TRS complaint changed from heartburn pre-GBP (96%) to regurgitation post-GBP (64%). Esophageal mucosa improved in 27, was unchanged in 51, and worsened in 8 patients (P = 0.001) in regard of esophagitis. Extraesophageal syndromes were present in 16 patients preoperatively and in none but one post-GBP (P = 0.0003). GERD-related well being and use of proton pump inhibitors were both improved after GBP. Total acid exposure decreased from a median (interquartile range, 25%-75%) of 5.1% (range, 2-8.2) to 1.1% (range, 0.2-4.8), P = 0.0002. Most patients (86%) showed and acid gastric pouch in fasting conditions post-GBP.

Conclusions: GBP ameliorated GERD syndromes in most patients 6 months after the procedure, resulting in quality of life improvement and less proton pump inhibitors usage. Whether regurgitation post-GBP corresponds to reflux disease or bad eating behavior deserves further studies.
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http://dx.doi.org/10.1097/SLA.0b013e3181bdff20DOI Listing
February 2010

Cytokine genes are associated with tuberculin skin test response in a native Brazilian population.

Tuberculosis (Edinb) 2010 Jan 14;90(1):44-9. Epub 2009 Dec 14.

Departamento de Genética, Instituto de Biociências, UFRGS, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501 970 Porto Alegre, RS, Brazil.

Tuberculosis was a major cause of population decline among Brazilian indigenous peoples and remains a leading cause of morbidity and mortality among them. Despite high BCG coverage, results of Tuberculin Skin Test (TST) reactivity have shown high rates of anergy in Amazonian Indians. Given the high prevalence of anergy in these populations and the fact that genetic host factors play an important role in susceptibility to Mycobacterium tuberculosis (MTB), the aim of this study was to evaluate the association of nineteen polymorphisms in fifteen genes related to immune response and anergy in the Xavante, an indigenous group from Brazil. A total of 481 individuals were investigated. TST anergy was observed in 69% of them. Polymorphisms in four genes showed absence or very low variability: SP110, PTPN22, IL12RB1 and IL6. IFNG +874 A/T heterozygotes and IL4-590 C/C homozygotes were more frequent in those individuals who presented a positive TST (prevalence ratios of 1.9 and 2.0 respectively). The risk of anergy was 1.5 in IL10-1082 G/G homozygotes when compared to carriers for the A allele. In indigenous groups such as the Xavante exposure to a variety of infections, associated with specific genetic factors, may disturb the T-helper 1 and T-helper 2 balance leading to increased immunological susceptibility.
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http://dx.doi.org/10.1016/j.tube.2009.11.002DOI Listing
January 2010