CCR5Δ32 and HLA allele diversity in bone marrow donors from southern Brazil.

Transplantation of stem cells derived from donors with CCR5Δ32 homozygous genotype is a potential strategy to achieve both the control of malignant hematological disease as well as sustained remission of the HIV infection, and researchers in different countries are looking for CCR5Δ32 homozygous donors to replicate such a 'double-target' strategy. We determined the frequency of the CCR5Δ32 variant in a sample of 1,398 bone marrow donors from Rio Grande do Sul State, Brazil. This study also evaluated whether HLA-A, HLA-B and HLA-DRB1 genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers in a population characterized by a significant genetic admixture. The CCR5Δ32 allele frequency was 7.4% (CI0.95 6.4-8.4%), and the frequency of the Δ32/Δ32 homozygous genotype was 0.72% (CI0.95 0.34-1.31%). In general, HLA genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers. Considering the large number of bone marrow donors in Brazil and the high CCR5Δ32 allele frequency observed in our study, our results clearly indicate the existence of a considerable amount of potential CCR5Δ32 homozygous bone marrow donors in southern Brazil, suggesting that an active search for these donors is not only feasible but an attractive and promising strategy towards effective HIV infection control and treatment.

Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma.

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive 5 years after diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is needed. Autophagy is a physiological mechanism involved in the turnover of cellular components that plays a key role in cancer. This study evaluated the differential levels of three key regulators of autophagy (SQSTM1, MAP1LC3B, and BECN1) in patients with ESCC, associating autophagy with histopathologic features, including the grade of differentiation, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. Nuclear morphometry of the tumor parenchyma was also assessed, associating it with autophagy and histopathology. All three markers significantly increased in patients with ESCC compared to the control group. Based on the mean expression of each protein in the control group, 57% of patients with ESCC had high levels of all three markers compared to control patients (14%). The most frequent profiles found in ESCC were BECNhigh/MAP1LC3high and BECNhigh/SQSTM1high. According to the TCGA database, we found that the main autophagy genes were upregulated in ESCC. Moreover, high levels of autophagy markers were associated with a poor prognosis. Considering nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which was strongly negatively correlated with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while poorly differentiated tumors showed lower SQSTM1 levels. ESCC progression may involve increased autophagy and changes in nuclear structure, associated with clinically relevant histopathological features. KEY MESSAGES: Autophagy markers are co-increased in primary ESCC. Autophagy negatively correlates with nuclear morphometry in ESCC parenchyma. Autophagy and nuclear morphometry are associated with histopathological features. Autophagy is increased in ESCC-TCGA database and associated with poor prognosis.

Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses.

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children's non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.

Predictors of dental erosions in patients evaluated with upper digestive endoscopy: a cross-sectional study.

The most studied medical condition related with dental erosions is gastroesophageal reflux disease (GERD). The aim of this study was to assess other predictors of dental erosions besides GERD in outpatients referred for upper digestive endoscopy. In a cross-sectional study, we prospectively evaluated 235 patients who underwent upper digestive endoscopy. Patients were interviewed and examined by a trained dentist before the endoscopies, addressing dental health as well as clinical information and food intake. Dental erosion was classified using Basic Erosive Wear Examination score. Potential predictors for dental erosions were: gender, age, chronic use of antidepressants and proton pump inhibitors (PPI), diabetes mellitus, body mass index, heartburn and acid regurgitation scores, chocolate intake, reflux esophagitis and hiatal hernia. Overall prevalence of dental erosions was 23.4%. The most parsimonious Poisson regression model for dental erosions considered age, chocolate intake and acid regurgitation as predictors. Dental erosions were associated with acid regurgitation in patients younger than 50 years [adjusted prevalence ratio (PR) = 1.8 (95% CI 1.1-2.9)] and with chocolate intake in patients older than 50 years [PR = 2.1 (95% CI 1.2-3.9]. The surfaces most eroded were palatine/lingual (n = 25) and occlusal (n = 25), followed by vestibular (n = 5). In outpatients evaluated with upper digestive endoscopy, the variables associated with dental erosions were age younger than 50 years, acid regurgitation and chocolate intake. Referral for dental evaluation should be considered for young patients with GERD and frequent acid regurgitation.

Polymorphisms in CYP19A1 and NFKB1 genes are associated with cutaneous melanoma risk in southern Brazilian patients.

BACKGROUND: Melanoma is the leading cause of death from skin cancers and its etiology is complex. Recent discoveries related to genetic risk factors are helping us to understand melanoma pathogenesis better. Nuclear factor-κB (NF-κB) has a critical role in immunity, inflammation, and tumor growth. The 94ins/del ATTG (rs28362491) polymorphism located in the NFKB1 gene has been associated to various cancers and the ATTG2/ATTG2 genotype was correlated to melanoma risk in Sweden. The CYP19A1 gene encodes the enzyme aromatase, which is active in malignant melanoma tissue. In addition, the CYP19A1 TCT insertion/deletion variant in intron 4 (rs11575899) has been associated with an increased incidence of cancer, albeit with conflicting results. The goal of this study was to investigate possible associations between these two gene variants and melanoma. METHODS: In this case-control study, we evaluated 117 cutaneous melanoma patients and 116 controls from southern Brazil. Genotyping of rs28362491 and rs11575899 was carried out by means of PCR amplification and capillary electrophoresis. Logistic regression was used to obtain odds ratios (ORs) of melanoma, according to genotypes. RESULTS: We identified an association between the ATTG2/ATTG2 and melanoma [OR=1.78; 95% confidence interval (CI): 1.06-3.00; P=0.03]. In addition, there was a dose effect: for each ins allele in the genotype, the risk for melanoma increased (OR=1.51; 95% CI: 1.08-2.11; P=0.017). As regards the CYP19A1 variant, genotype 11 (del/del) was more frequent in patients than in controls (OR=1.85; 95% CI 1.06-3.22; P=0.03). CONCLUSION: The NFKB1 ATTG2/ATTG2 and CYP19A1 del/del genotypes are significantly associated with melanoma and could be genetic markers of melanoma susceptibility in southern Brazilian population.

Health-related uuality of life of pregnant women with heartburn and regurgitation / Qualidade de vida em gestantes com pirose e regurgitação

Background Heartburn and regurgitation frequently occur in the third trimester of pregnancy, but their impact on quality of life has not been thoroughly investigated. Objective To measure health-related quality of life of third-trimester pregnant women with heartburn and regurgitation. Methods Data on obstetric history, heartburn and regurgitation frequency and intensity, history of heartburn and regurgitation and health-related quality of life were collected of 82 third-trimester pregnant women. Results Sixty-two (76%) women had heartburn, and 58 (71%), regurgitation; 20 were asymptomatic. Mean gestational age was 33.8±3.7 weeks; 35 (43%) women had a family history of heartburn and/or regurgitation, and 57 (70%) were asymptomatic before pregnancy. The following quality of life concepts were significantly reduced: physical problems and social functioning for heartburn; physical problems and emotional functioning for regurgitation. There was agreement between heartburn in present and previous pregnancies. Conclusion Heartburn and/or regurgitation affected health-related quality of life of third trimester pregnant women .

Contexto A pirose e a regurgitação ocorrem com frequência no terceiro trimestre de gestação, mas o seu impacto na qualidade de vida não foi completamente investigado. Objetivo Avaliar a qualidade da vida de gestantes do terceiro trimestre com pirose e regurgitação. Métodos Os dados sobre a história obstétrica, frequência, intensidade e história de pirose e regurgitação, bem como a qualidade de vida foram coletados de 82 mulheres do terceiro trimestre de gestação. Resultados Sessenta e duas (76%) mulheres tinham pirose e, 58 (71%), regurgitação; 20 eram assintomáticas. A idade gestacional média foi de 33,8 ± 3,7 semanas; 35 (43%) mulheres tinham história familiar de pirose e/ou regurgitação e 57 (70%) eram assintomáticos antes da gestação. Os seguintes domínios de qualidade de vida estavam significativamente reduzidos: limitação física e aspectos sociais pela pirose; limitação física e aspectos emocionais pela regurgitação. Houve concordância entre pirose nas gestações atuais e prévias. Conclusão A pirose e/ou regurgitação afetam a qualidade de vida de gestantes de terceiro trimestre. .

Expression of cancer stem cell markers in basal and penta-negative breast carcinomas--a study of a series of triple-negative tumors.

PURPOSE: Breast cancer is a heterogeneous disease. Immunohistochemistry has given rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of neoplasia and its heterogeneity has been strongly debated in cancer stem cells (CSC) theme. This study investigates the prevalence of basal (BCC) and penta-negative carcinomas (5NC) in TNC and establishes associations with CSC (CD44CD24). MATERIALS AND METHODS: 94 TNC were tested for CK5/6, HER1, CD44 and CD24, evaluated by a simple immunohistochemistry score and correlated with clinicopathological and survival data. RESULTS: BCC had higher tumor grades than 5NC (p=0.004). CD44 negativity (p=0.007) and CD44(-)CD24(+) phenotype (p=0.013) were associated with less vascular invasion amongst TNC. CD44 expression was associated with BCC (p=0.007). CD44(-)CD24(-/low) phenotype was associated with 5NC. None of the variables were associated with clinical outcome. CONCLUSION: BCC and 5NC are closely related tumor subtypes. CD44(-)CD24(-/low) phenotype was associated with 5NC and CD44(-)CD24(+) phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.

Nuclear morphometric analysis (NMA): screening of senescence, apoptosis and nuclear irregularities.

Several cellular mechanisms affect nuclear morphology which can therefore be used to assess certain processes. Here, we present an analytic tool to quantify the number of cells in a population that present characteristics of senescence, apoptosis or nuclear irregularities through nuclear morphometric analysis. The tool presented here is based on nuclear image analysis and evaluation of size and regularity of adhered cells in culture. From 46 measurements of nuclear morphometry, principal component analysis filtered four measurements that best separated regular from irregular nuclei. These measurements, namely aspect, area box, radius ratio and roundness were combined into a single nuclear irregularity index (NII). Normal nuclei are used to set the parameters for a given cell type, and different nuclear phenotypes are separated in an area versus NII plot. The tool was validated with ß-gal staining for senescence and annexin or caspases inhibitor for apoptosis as well as several treatments that induce different cellular phenotypes. This method provides a direct and objective way of screening normal, senescent, apoptotic and nuclear irregularities which may occur during failed mitosis or mitotic catastrophe, which may be very useful in basic and clinical research.

Is there an association between hiatal hernia and ineffective esophageal motility in patients with gastroesophageal reflux disease?

INTRODUCTION: The pathophysiology of gastroesophageal reflux disease is multifactorial, where esophageal motility is one of the factors implicated in its genesis. However, there is still no consensus on the existence of an association between esophageal dysmotility and hiatal hernia in patients with gastroesophageal reflux disease. The objective of this study was to establish the prevalence of esophageal dysmotility in patients with hiatal hernia and to determine if herniation is a factor related to esophageal dysmotility in patients with gastroesophageal reflux disease. METHODS: The study included 356 patients with a clinical diagnosis of gastroesophageal reflux disease submitted to upper digestive endoscopy and esophageal functional diagnostics. Hiatal hernia was defined endoscopically by a distance equal to or greater than 2 cm between the diaphragmatic constriction and the squamocolumnar junction and esophageal dysmotility when the esophageal manometry identified the amplitude of the peristaltic waves in the distal esophagus as <30 mmHg and/or less than 80% of effective contractions. For univariate statistical analysis, the patients were divided into two groups: with and without hiatal hernia. Poisson regression models were used to estimate crude and adjusted prevalence ratios (PR) of esophageal dysmotility according to hiatal hernia. RESULTS: Gastroesophageal reflux disease patients with hiatal hernia had a prevalence of esophageal dysmotility equal to 14.8% and those without hiatal hernia, a prevalence of 7.7% (p = 0.041). Patients with hiatal hernia also showed a higher frequency of erosive esophagitis (47.5% versus 24.2%, p < 0.001), lower low esophageal sphincter pressure (10.4 versus 13.10; p < 0.001), and higher frequency of individuals with abnormal pH-metry values (p < 0.001). The crude PR for esophageal dysmotility, according to the presence of hiatal hernia, was 1.92 (confidence interval (CI), 1.04-3.53; p = 0.037), but this association did not persist when controlled for age, esophagitis, altered pH-metry, and altered low esophageal sphincter (adjusted PR, 1.69; CI, 0.68-4.15; p = 0.257). CONCLUSION: Despite the prevalence of esophageal dysmotility in the hiatal hernia group being higher than that in the group without hiatal hernia, the association between these variables in individuals with gastroesophageal reflux disease disappeared when controlling for age, esophagitis, altered pH-metry, and altered low esophageal sphincter, leading us to believe that in these patients, hiatal hernia is not an independent risk factor for dysmotility.

Evolução da prevalência de parasitoses intestinais em escolares em Caxias do Sul, RS / Evolution of the prevalence of intestinal parasitosis among schoolchildren in Caxias do Sul, RS

Relatos da prevalência das parasitoses intestinais no Brasil são pontuais e têm sido descritos em diferentes populações, tornando difícil um diagnóstico abrangente. Visando estudar a variação em 35 anos da prevalência de enteroparasitoses em escolares de Caxias do Sul, RS, foram avaliados 9.787 exames parasitológicos de fezes realizados por centrífugo-sedimentação. Resultaram positivas 5.655 (58 por cento) amostras sendo mais prevalente a infestação por Ascaris lumbricoides (47 por cento), Trichuris trichiura (36 por cento), Enterobius vermicularis (8 por cento) e os protozoários: Giardia lamblia (24 por cento) e Entamoeba coli (20 por cento). A prevalência geral diminuiu de 89 por cento para 37 por cento, com um decréscimo médio de 1,4 por cento ao ano. Houve redução na prevalência de Ascaris lumbricoides de 61 para 26 por cento e de Trichuris trichiura de 38 a 18 por cento. Para Giardia lamblia não houve alteração significativa. A prevalência de Entamoeba coli cresceu de 29 a 46 por cento. Os decréscimos obtidos na prevalência dos helmintos são provavelmente devidos às melhorias da infra-estrutura e às ações formativas desenvolvidas nas escolas.

Reports on the prevalence of intestinal parasitosis in Brazil have been local in nature, with descriptions of different populations, which makes comprehensive diagnosis difficult. With the aim of studying the variation in the prevalence of intestinal parasitosis among schoolchildren in Caxias do Sul, Rio Grande do Sul, over a 35-year period, 9,787 parasitological stool tests that had been performed using centrifugal sedimentation were evaluated. There were positive results from 5,655 samples (58 percent), and the most prevalent infestations were of Ascaris lumbricoides (47 percent), Trichuris trichiura (36 percent), Enterobius vermicularis (8 percent) and the protozoa Giardia lamblia (24 percent) and Entamoeba coli (20 percent). The overall prevalence diminished from 89 percent to 37 percent, indicating an average decrease of 1.4 percent per year. Reductions in prevalence were observed for Ascaris lumbricoides (61 to 26 percent) and Trichuris trichiura (38 to 18 percent). No significant change was observed for Giardia lamblia. The prevalence of Entamoeba coli increased from 29 to 46 percent. The decreases in helminth prevalence were probably due to infrastructure improvements and educational actions undertaken in schools.

Prospective evaluation of pregnant women vaccinated against rubella in southern Brazil.

The rubella virus is a potent human teratogen. The highest risk of this infection occurs during pregnancy, as the virus may cause fetal damage known as congenital rubella syndrome (CRS). Since the rubella vaccine is made with attenuated live virus, there is a high level of anxiety concerning exposure during pregnancy. Although no case of CRS has been proved in children of immunized susceptible pregnant women, a risk below 1.6% cannot be ruled out. Our main purpose was to evaluate the occurrence of CRS in women who were vaccinated against rubella and did not know that they were pregnant, or became pregnant within 30 days after vaccination. We collected, prospectively, data on 171 pregnant women who were susceptible at the time of vaccination and compared them with data on the total population of pregnant women in the state of Rio Grande do Sul (RS), Brazil. A serologic sample was collected in 149 infants of susceptible mothers. A total of 10 infants (6.7%) had anti-rubella antibodies. When these were compared with the results obtained in the total population of births in RS, no difference was found in mean birth weight, low birth weight and sex. None of the ten infants with IgM(+) presented congenital defects involving CRS, during the physical examinations performed at the time of birth and at 3 months of age. Our study allows the safety of rubella vaccination to be extended to pregnant women.

Effect of temperature shock on soybean microspore embryogenesis

Neste estudo foram testados os efeitos do choque térmico na indução androgenética em cultura de anteras de soja. Parte das anteras formam submetidas ao choque térmico de 4 ou 33ºC, enquanto as anteras controle formam mantidas a 25ºC. Análises citológicas formam realizadas ao longo dos 30 primeiros dias de cultura mostrando que a freqüência de grãos de pólen binucleados simétricos e multinucleados não difere entre os tratamentos e que os grãos de pólen multinucleados podem ser formados tanto a partir de uma mitose simétrica inicial como após uma mitose assimétrica. Em relação à indução embriogênica, os tratamentos também não diferem. Estes resultados sugerem que o tratamento de choque térmico não induz a rota esporofítica nos micrósporos de soja.

Association between floral bud size and developmental stage in soybean microspores

This study was carried out to establish the association between floral bud size and the corresponding microspore developmental stages for Brazilian soybean cultivars. Microspore developmental stage distributions were examined in young buds from cv Década, IAS5 and RS7. The data indicated that for a given bud-size group, the microspores of different cultivars were at different developmental stages, with cv RS7 and Década distributed at the youngest and cv IAS5 at the most advanced stages. Microspore stages distribution were also compared among the ten anthers of the same bud of the above cultivars. The ten anthers from a given bud were clearly distributed at different developmental stages. Caution should be exercised when adopting the standard anther culture practice of using the microspore stage of one anther to represent the entire bud