Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CßS, MTHFR, NOS3, CYBA, and ACE1.

OBJECTIVE: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CßS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. METHODS: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher's exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. RESULTS: Results revealed that CßS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CßS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]). CONCLUSIONS: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.

Perfil Epidemiológico da Violência no Estado de São Paulo em Comparação ao Departamento Regional de Saúde II / Epidemiological Profile of Violence in the State of Sao Paulo Compared to a Regional Health Department II

Introdução: A violência sempre esteve presente na história da humanidade e consiste no uso de poder ou força física contra si mesmo ou contra outros, ou grupos, que resulte em algum tipo de dano ou até em morte. Objetivo: O objetivo deste artigo é caracterizar o perfil epidemiológico da violência no estado de São Paulo e no Departamento Regional de Saúde II e comparar a incidência das notificações entre 2011 e 2021. Métodos: Trata-se de um estudo longitudinal retrospectivo com dados provenientes do DATASUS. Foram calculadas as frequências relativas das variáveis das vítimas e dos agressores. Resultados: Identificou-se que na região e no departamento estudados houve predomínio da violência física, com a maioria das vítimas pertencentes ao sexo feminino e à raça branca. Em geral, a agressão foi cometida pelo cônjuge, dentro da residência. No quesito faixa etária, houve diferença entre estado e DRS II, com preponderância das idades entre 15 a 29 anos e 30 a 59 anos, respectivamente. Nas variáveis escolaridade da vítima e ciclo de vida do autor, observou-se que a maior porcentagem das fichas se enquadraram na categoria branco/ignorado/não se aplica. Conclusão: Ao comparar a incidência das notificações de violência entre ambos, concluiu-se que não houve diferença significativa (p > 0,05). A caracterização do perfil epidemiológico é essencial para o combate à violência, pois possibilita a implementação de políticas públicas, bem como a identificação de fragilidades relacionadas ao preenchimento da ficha de notificação individual.

Introduction: Violence has always been present in history and consists of the use of power or physical force against oneself or against others, or groups, resulting in some kind of harm or even death. Objective: The objective of this article is to characterize the epidemiological profile of violence in the state of São Paulo and in the DRS II region and compare the incidence of notifications between 2011 and 2021. Methods: This is a retrospective longitudinal study using data from DATASUS. The relative frequencies of victim and aggressor variables were calculated. Results: It was identified that in both regions studied, physical violence predominated, with the majority of victims being female and white. In general, the aggression occurred within the home by the spouse. There was a difference in age group between the state and DRS II, with predominance of ages between 15 to 29 years and 30 to 59 years, respectively. In terms of victim's education level and author's life cycle variables, the highest percentage of records fell into the category of white/unknown/not applicable. Conclusion: When comparing the incidence of violence notifications between both regions, it was concluded that there was no significant difference (p>0.05). Characterizing the epidemiological profile is essential to combat violence, as it enables the creation of public policies, as well as identifying weaknesses related to the completion of the Individual Notification Form.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Macroscopic Evaluation of Atherosclerosis in the Arteries: An Autopsy Assessment Tool. / Avaliação Macroscópica da Aterosclerose nas Artérias: Uma Ferramenta de Avaliação na Autópsia.

BACKGROUND: Atherosclerosis, in some cases, is an asymptomatic condition, and it is important to know the degree of arterial impairment caused by plaques and its association with risk factors. Autopsy examination provides understanding of basic disease processes and assessment to data about macroscopic characteristic of atherosclerotic involvement. OBJECTIVE: To macroscopically assess and standardize atherosclerotic involvement of aorta, carotid and iliac arteries and compare with age, gender and causes of death. METHODS: We collected 53 aortic arteries, 53 right carotid arteries, 53 left carotid arteries, 53 right iliac arteries and 53 left iliac arteries. For this assessment, the extension of fatty streaks, atheromatous plaques, fibrosis and calcification were considered, being the reference to score the degree of atherosclerotic involvement. Many degrees of atherosclerosis and accurate values were observed for mild, moderate and severe classification. For statistical analysis, data were analyzed using the software GraphPad Prism® 7.0. Differences were considered statistically significant if p-value was less than 5% (p <0.05). RESULTS: Carotid arteries had greater atherosclerotic involvement compared to the other arteries (K = 15.73, p = 0.0004). Atherosclerosis was progressive and significant with increasing age (carotid arteries: t = 6.321; p <0.0001; aorta: U = 83.5; p <0.0001; iliac: U = 306; p <0.0001) and as cause of cardiovascular death (carotids: t = 5.047; p <0.0001; aorta: U = 98.5; p = 0.0068; iliac: U = 467.5; p = 0.0012). CONCLUSION: Macroscopic assessment of atherosclerosis is an innovative and low-cost way of direct visualization of atherosclerotic plaques, enabling an association with risk factors such as increasing age and cardiovascular diseases, providing important data for clinical practice.

FUNDAMENTO: A aterosclerose, em alguns casos, é uma condição assintomática, sendo necessário conhecer o grau de comprometimento arterial provocado pelas placas e sua associação com os fatores de risco. O exame de autópsia permite a compreensão dos processos básicos de doenças, assim como a avaliação e fornecimento de dados sobre a característica macroscópica do acometimento aterosclerótico. OBJETIVO: Avaliar macroscopicamente e padronizar o acometimento aterosclerótico das artérias aorta, carótidas e ilíacas e comparar com a idade, o sexo e a causa de morte. MÉTODOS: Foram coletados 53 artérias aorta, 53 artérias carótida direita, 53 artérias carótida esquerda, 53 artérias ilíaca direita e 53 artérias ilíaca esquerda. Para essa avaliação, foi considerada a extensão de estrias lipídicas, de placas ateromatosas, de fibrose e de calcificação, as quais serviram de referência para pontuar a intensidade do acometimento aterosclerótico. Foram observados vários graus da aterosclerose e valores acurados para a classificação discreta, moderada e acentuada. Para a análise estatística, os dados foram analisados utilizando-se o software GraphPad Prism ® 7.0. As diferenças foram consideradas estatisticamente significativas quando "p" foi menor que 5% (p<0,05). RESULTADOS: As artérias carótidas apresentaram maior acometimento aterosclerótico em comparação às outras artérias avaliadas (K=15,73, p=0,0004). A ocorrência da aterosclerose se mostrou progressiva e significativa com o decorrer da idade (carótidas: t=6,321; p<0,0001; aortas: U=83,5; p<0,0001; ilíacas: U=306; p<0,0001) e na causa de morte cardiovascular (carótidas: t=5,047; p<0,0001; aortas: U=98,5; p=0,0068; ilíacas: U=467,5; p=0,0012). CONCLUSÃO: A avaliação macroscópica da aterosclerose trata-se de uma forma inovadora e de baixo custo de avaliação através da visualização direta das placas ateroscleróticas, possibilitando uma associação com fatores de risco como idade avançada e doenças cardiovasculares, fornecendo dados importantes para a prática clínica.

Avaliação Macroscópica da Aterosclerose nas Artérias: Uma Ferramenta de Avaliação na Autópsia / Macroscopic Evaluation of Atherosclerosis in the Arteries: An Autopsy Assessment Tool

Resumo Fundamento A aterosclerose, em alguns casos, é uma condição assintomática, sendo necessário conhecer o grau de comprometimento arterial provocado pelas placas e sua associação com os fatores de risco. O exame de autópsia permite a compreensão dos processos básicos de doenças, assim como a avaliação e fornecimento de dados sobre a característica macroscópica do acometimento aterosclerótico. Objetivo Avaliar macroscopicamente e padronizar o acometimento aterosclerótico das artérias aorta, carótidas e ilíacas e comparar com a idade, o sexo e a causa de morte. Métodos Foram coletados 53 artérias aorta, 53 artérias carótida direita, 53 artérias carótida esquerda, 53 artérias ilíaca direita e 53 artérias ilíaca esquerda. Para essa avaliação, foi considerada a extensão de estrias lipídicas, de placas ateromatosas, de fibrose e de calcificação, as quais serviram de referência para pontuar a intensidade do acometimento aterosclerótico. Foram observados vários graus da aterosclerose e valores acurados para a classificação discreta, moderada e acentuada. Para a análise estatística, os dados foram analisados utilizando-se o software GraphPad Prism ® 7.0. As diferenças foram consideradas estatisticamente significativas quando "p" foi menor que 5% (p<0,05). Resultados As artérias carótidas apresentaram maior acometimento aterosclerótico em comparação às outras artérias avaliadas (K=15,73, p=0,0004). A ocorrência da aterosclerose se mostrou progressiva e significativa com o decorrer da idade (carótidas: t=6,321; p<0,0001; aortas: U=83,5; p<0,0001; ilíacas: U=306; p<0,0001) e na causa de morte cardiovascular (carótidas: t=5,047; p<0,0001; aortas: U=98,5; p=0,0068; ilíacas: U=467,5; p=0,0012). Conclusão A avaliação macroscópica da aterosclerose trata-se de uma forma inovadora e de baixo custo de avaliação através da visualização direta das placas ateroscleróticas, possibilitando uma associação com fatores de risco como idade avançada e doenças cardiovasculares, fornecendo dados importantes para a prática clínica.

Abstract Background Atherosclerosis, in some cases, is an asymptomatic condition, and it is important to know the degree of arterial impairment caused by plaques and its association with risk factors. Autopsy examination provides understanding of basic disease processes and assessment to data about macroscopic characteristic of atherosclerotic involvement. Objective To macroscopically assess and standardize atherosclerotic involvement of aorta, carotid and iliac arteries and compare with age, gender and causes of death. Methods We collected 53 aortic arteries, 53 right carotid arteries, 53 left carotid arteries, 53 right iliac arteries and 53 left iliac arteries. For this assessment, the extension of fatty streaks, atheromatous plaques, fibrosis and calcification were considered, being the reference to score the degree of atherosclerotic involvement. Many degrees of atherosclerosis and accurate values were observed for mild, moderate and severe classification. For statistical analysis, data were analyzed using the software GraphPad Prism® 7.0. Differences were considered statistically significant if p-value was less than 5% (p <0.05). Results Carotid arteries had greater atherosclerotic involvement compared to the other arteries (K = 15.73, p = 0.0004). Atherosclerosis was progressive and significant with increasing age (carotid arteries: t = 6.321; p <0.0001; aorta: U = 83.5; p <0.0001; iliac: U = 306; p <0.0001) and as cause of cardiovascular death (carotids: t = 5.047; p <0.0001; aorta: U = 98.5; p = 0.0068; iliac: U = 467.5; p = 0.0012). Conclusion Macroscopic assessment of atherosclerosis is an innovative and low-cost way of direct visualization of atherosclerotic plaques, enabling an association with risk factors such as increasing age and cardiovascular diseases, providing important data for clinical practice.

Differences in the genotype frequencies of genes related to blood pressure regulation - a comparative study between South-West Europe and Peri-equatorial Africa.

Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of environments, facing different selective pressures. Objectives: The aim this study is to compare genotype frequencies between South-West Europe and Peri-equatorial Africa in genes potentially modulators of blood pressure. Methods: The analyzed sample consisted of 325 individuals from Portugal and 226 individuals from Africa (48 from Mozambique and 178 from São Tomé and Príncipe). The following genetic variants were analyzed: intron 4 VNTR in eNOS, rs1050829 in G6PD, -3.7kb α-thalassemic deletion in HBA, rs1800457 in CYB5R3, Hp 1/2 genotype/phenotype in Hp and intron 16 I/D in ACE. Results: Frequencies of genotypes with the 4a allele in eNOS (p<0.001), the G allele in G6PD (p<0.001), the α-3.7 kb in HBA (p <0.001), the C allele in the CYB5R3 (p<0.001) were higher in Peri-equatorial Africa. The Hp 1.1 genotype of Hp has a higher frequency in Peri-equatorial Africa (p=0.002). ACE shows no significant differences. Conclusion: Results show differences in five genetic variants. Conditions of extreme heat and humidity, characteristic of Peri-equatorial Africa, have been associated with increased sodium loss. This study suggests that selected compensatory mechanisms printed in the genome, are nowadays risk factors for hypertension in Peri-equatorial Africa.

Morphological and Histopathological Study of Autopsied Patients with Atherosclerosis and HIV.

BACKGROUND: Chronic infection by HIV evolves with a vascular inflammatory action causing endothelial dysfunction. The action of the virus, as well as the side effects of antiretroviral drugs, contribute to the progression of cardiovascular diseases. The present study aimed to evaluate the percentage of collagen fibers and the density of mast cells, chymase and tryptase, in aortas of patients with and without HIV, and also patients with and without atherosclerosis. METHODS: Aortic fragments were obtained from autopsied patients aged 22-69 years and selected regardless of the cause of death or underlying disease. The samples were divided into four groups, (1) Group with HIV and with atherosclerosis; (2) Group with HIV and without atherosclerosis; (3) Group without HIV and with atherosclerosis; (4) Group without HIV and without atherosclerosis (Control). The percentage of collagen fibers was analyzed in the intima-media layer and the density of mast cells was analyzed in all aortic layers. Graphpad Prism 5.0® software was used for statistical analysis. RESULTS: There were more collagen fibers in HIV patients, with or without atherosclerosis. The group with HIV and atherosclerosis presented a higher density of chymase and tryptase mast cells. The correlation between collagen fibers and age was negative in the non-HIV group and with atherosclerosis. CONCLUSION: The inflammatory process resulting from HIV infection may be relevant in the alteration of aortic collagen fibers and in triggering or accelerating atherosclerosis. The study is important because HIV patients have increased risks for the development of cardiovascular diseases, and follow-up is necessary to prevent such diseases.

Metabolic Dysfunction and Asthma: Current Perspectives.

The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.

Impact on Longevity of Genetic Cardiovascular Risk and Lifestyle including Red Meat Consumption.

BACKGROUND: Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk. OBJECTIVES: The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity. METHODS: A case-control study involving 521 both gender individuals, 253 centenarians (100.26 ± 1.98 years), and 268 controls (67.51 ± 3.25 years), low (LCR, n = 107) and high (HCR, n = 161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994, AGT-rs4762, AGR1-rs5182, GRK4-rs2960306, GRK4-rs1024323, NOS3-rs1799983, and SLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®. RESULTS: Antilongevity factors consisted (OR 95% CI, p < 0.05) BMI 1.558 (1.445-1.680), hypertension 2.358 (1.565-3.553), smoking habits 4.528 (2.579-7.949), diabetes 5.553 (2.889-10.675), hypercholesterolemia 1.016 (1.010-1.022), and regular consumption of red meat 22.363 (13.987-35.755). Genetic aspects particularly for HCR individuals ACE II (OR: 3.96 (1.83-8.56), p < 0.0001) and NOS3 TT (OR: 3.11 (1.70-5.70), p < 0.0001) genotypes were also risk associate. Obesity, smoking, hypercholesterolemia, and frequent consumption of red meat have an additive action to hypertension in the longevity process. There was a synergistic interaction between the endothelial NOS3 genotypes and the severity of arterial hypertension. An epistatic interaction between functional genetic variants of GRK4 and angiotensinogen was also observed. CONCLUSIONS: Cardiovascular risk-related genetic and multifactorial or predominantly lifestyle aspects and its interactions might influence the aging process and contribute to exceptional longevity in Portuguese centenarians. Besides lifestyle, the activity of nitrite oxide synthase may be one of the main physiologic regulators of cardiovascular protection in the path of longevity.

Computerized morphometry of the area of the hard palate and of palatal rugae: a cross-sectional study / Morfometría computarizada del área del paladar duro y de las arrugas palatinas: un estudio transversal

Abstract Background: The evaluation of palatal rugae in human identification is important because these structures can remain intact for up to seven days after death. Aim: To compare the area and density of the palatal rugae between ages groups and genders. Settings and Design: A cross-sectional study. Methods and Material: Dental plaster models obtained from patients at the Orthodontic Clinic of University of Uberaba were selected. Two hundred patients were divided into four groups: Group 1:10-15 years; Group 2:16-30 years; Group 3:31-50 years; and Group 4:51-70 years. The palatal rugae and hard palate of each plaster model were outlined and photographed. The evaluation of the area of the hard palate and palatal rugae was performed using the ImageJ software. Statistical analysis used: Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square and Spearman correlation tests using GraphPad Prism 5 statistical software. Results and conclusión: The areas of the palatal rugae and of the hard palate were significantly smaller in the group 4. There was a significant negative correlation between age and palatal rugae area, and between age and hard palatal area. The present study was the first to demonstrate that patients between 51 and 70 years have a smaller palatal rugae area and a smaller hard palate area when compared to other groups. Thus, the evaluation of the hard palate area and of palatal rugae could be used as an adjunct with other methods to determine the age group of an individual; however studies using larger sample size are needed to validate this observation.

Morphological and histopathological evaluation of autopsied patients with hypertensive cardiopathy.

BACKGROUND: Physiopathological processes in hypertensive heart disease are controlled by complex interactions between cardiomyocytes, extracellular matrix, microvasculature and other cells present in the myocardium. OBJECTIVE: To analyze morphological changes in hypertensive cardiopathy and to describe and compare findings in order to help clarify determinant factors. METHODS: 42 fragments of the left ventricular myocardium and circumflex branch of the left coronary artery were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period ranging from 1984 to 2018. Groups were split into individuals with hypertensive heart disease (HD) and individuals without heart disease (ND). Wall thickness was measured with a digital caliper and Computed Tomography. Quantification of collagen fibers was conducted by computerized morphometry and mast cell density was assessed by immunohistochemical methods. RESULTS: There was a significant increase of heart weight in the HD group compared to the ND group, (p = 0.0002). There was a significant increase of thickness of the middle third of the free wall in the HD group compared to the ND group, (p = 0.04). There was a significant increase of collagen fibers in the left ventricle in the HD group compared to the ND group, (p < 0.0001). Concerning mast cell density, there was a significant increase in the left ventricle of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p < 0.0001). There was a significant increase of mast cell density in the circumflex branch of the left coronary artery of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p = 0.01). CONCLUSIONS: Mast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.

Interaction between HFE and haptoglobin polymorphisms and its relation with plasma glutathione levels in obese children.

Obesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress.  In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin - and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in childhood obesity.

Hypertension and longevity: role of genetic polymorphisms in renin-angiotensin-aldosterone system and endothelial nitric oxide synthase.

Hypertension (HT), a common age-related disorder, is an important risk factor for cardiovascular disease. This study aims to identify the prevalence of HT in Portuguese centenarians and evaluate whether gene polymorphisms encoding key molecules in blood pressure (BP) regulation are associated with longevity. There were recruited 253 centenarians (100.26 ± 1.98 years) and 268 control subjects (67.51 ± 3.25 years). Hypertension (ESH/ESC2013 and JNC8) and diabetes (WHO) were evaluate. Genetic polymorphisms of renin-angiotensin-aldosterone system (RAAS) and NOS3 were determined. The prevalence of HT among centenarians was 64.4% and the majority (58.9%) were controlled, differing from control group both on frequency (P < 0.001) and on their control (P < 0.001). We found that HT is a risk factor for not achieving longevity (OR 2.531, 95% CI 1.688-3.793, P < 0.001), the same for diabetes (OR 5.669 95% CI 2.966-10.835, P < 0.001), and male gender (OR 2.196, 95% CI 1.493-3.29, P < 0.001). Hypertension, adjusted for gender and diabetes, was independent risk factor anti-longevity (OR 2.007, 95% CI 1320-3.052, P = 0.001). The ACE_D and NOS3_G alleles were more frequent in centenarians compared to controls (P < 0.001, both cases). ACE_II and NOS3_TT genotypes, adjusted for BP, gender and diabetes, increased risk in 3.748 (95% CI 1.887-7.444) and 2.533 (95% CI 1.483-4.327), respectively, in relation to ACE_DD (P < 0.001) and NOS3_GG (P = 0.001), against longevity. Our findings suggest that the prevalence of hypertension was lower in Portuguese centenarians than in the elderly, reinforcing the importance of better cardiovascular risk profiles to achieve longevity even in the presence of genetic condition.

Tongue development in stillborns autopsied at different gestational ages / Desenvolvimento da língua em natimortos autopsiados em diferentes idades gestacionais

Abstract Objectives: This study aimed to analyze, through the morphometric method, the perimeter and length of the tongue, the collagen fibers, and the perimeter of blood vessels at different gestational ages and fetal weights. Material and methods: Tongues (n = 55) of stillborns autopsied at 23-40 weeks of gestational age were macroscopically analyzed, and their length and perimeter were measured. Fifty-five tongue fragments were collected through a longitudinal section in the region that accompanies the median lingual sulcus and histologically processed. Slides were stained with picrosirius and immunolabeled with CD31 antibody. Quantification was performed on collagen fibers under polarized light, and on the perimeter of vessels with the CD31. Results: A positive and significant correlation of gestational age with tongue perimeter and length was found. There was a positive and significant correlation between collagen fibers and gestational age, as well as between gestational age and the perimeter of blood vessels. Between collagen fibers and fetal weight, a positive and significant increase was observed. Regarding the correlation between the perimeter of blood vessels and the fetal weight, an increase was observed. Conclusion: As gestational age advances, there is an increase in tongue perimeter and length, in the percentage of collagen fibers, and in vascular perimeter, demonstrating that tongue formation is directly related to tongue growth and development.

Resumo Objetivo: Analisar, por meio do método morfométrico, o perímetro e o comprimento da língua, as fibras de colágeno, o perímetro dos vasos sanguíneos, em idades gestacionais e de acordo com o peso fetal. Materiais e métodos: Línguas (n = 55) de natimortos autopsiados com 23-40 semanas de idade gestacional foram analisadas macroscopicamente, medidas em comprimento e perímetro; 55 fragmentos das línguas foram coletados por meio de uma secção longitudinal na região que acompanha o sulco lingual médio e processados histologicamente. As lâminas foram coloridas com picrosirius e imunomarcadas com o anticorpo CD31. A quantificação foi feita em fibras de colágeno examinadas com microscópio de luz polarizada e o perímetro dos vasos com o CD31. Resultados: Foi encontrada uma correlação positiva e significativa da idade gestacional com o perímetro e o comprimento da língua. Houve uma correlação positiva e significativa entre as fibras de colágeno e a idade gestacional; bem como entre a idade gestacional e o perímetro dos vasos sanguíneos; e houve um aumento positivo e significativo entre as fibras de colágeno e o peso fetal. No que diz respeito à correlação entre o perímetro dos vasos sanguíneos e o peso fetal, houve um aumento. Conclusão: Conforme a idade gestacional avança, há um aumento no perímetro e no comprimento da língua, um aumento no percentual de fibras de colágeno e um aumento no perímetro vascular, demonstra que a formação da língua está diretamente relacionada ao crescimento e ao desenvolvimento da língua.

Analysis of the collagen fibers on autopsied patients' uterus with the Acquired Immunodeficiency Syndrome / Análise das fibras colágenas do útero de pacientes autopsiadas com a Síndrome da Imunodeficiência Adquirida

Abstract Objectives: to compare the percentage of collagen fibers in the autopsied women's uterine body and cervix with and without the Acquired Immunodeficiency Syndrome (Aids). Methods: 30 autopsied women's medical files were selected from 1988 to 2013. 30 fragments of the uterine body and 30 cervix were collected and then divided into two groups, 15 with Aids and 15 without, The quantification of the collagen fibers of the uterine body and cervix was performed on slides stained with picrosirius, using the KS-300® system. Results: the percentage of collagen fibers was lower for cervix (U=336544; p=0.001) and higher for the uterine body (U=308726,5; p=0.004) in the retroviral group when compared to the group without the disease. The percentage was higher for cervix than the uterine body in the group with Aids (t=0,4793; p=0.0031). the same result was found in the group without Aids (t=2,397; p=0.0637). Conclusions: the increase in the percentage of collagen fibers in the uterine body of women with Aids' indicates an immune response for viral infection and reveals a failure in keeping the infection restricted to the cervix. The interpretation of the histochemical and morphometric parameters can be useful in the diagnosis associated to HIV infection, contributing for clinical improvement and life expectancy.

Resumo Objetivos: comparar a porcentagem de fibras colágenas no corpo e colo uterino de mulheres autopsiadas com e sem a Síndrome da Imunodeficiência Adquirida (Aids). Métodos: foram selecionados 30 prontuários de mulheres autopsiadas no período de 1988 a 2013. Foram coletados 30 fragmentos do corpo uterino e 30 do colo uterino, dividido em dois grupos, 15 com Aids e 15 sem. A quantificação das fibras colágenas do corpo e colo uterino foi feita nas lâminas coradas por picrosirius, utilizando-se o sistema KS-300®. Resultados: a porcentagem de fibras colágenas foi menor no colo (U=336544; p=0,001) e maior no corpo uterino (U=308 726,5; p=0,004) no grupo com a retrovirose quando comparado ao grupo sem a doença. A porcentagem no grupo com Aids foi maior no colo uterino do que no corpo (t=0,4793; p=0,0031). Sendo o mesmo resultado encontrado para o grupo sem Aids (t=2.397; p=0,0637). Conclusões: um aumento da porcentagem de fibras colágenas no corpo uterino das mulheres com Aids indica uma resposta imune frente a infecção viral e revela uma falha em manter a infecção restrita ao colo. A interpretação dos parâmetros histoquímicos e morfométricos podem ser úteis no diagnóstico das condições associadas à infecção pelo HIV, contribuindo para a melhora clínica e expectativa de vida.

Tongue development in stillborns autopsied at different gestational ages.

OBJECTIVES: This study aimed to analyze, through the morphometric method, the perimeter and length of the tongue, the collagen fibers, and the perimeter of blood vessels at different gestational ages and fetal weights. MATERIAL AND METHODS: Tongues (n=55) of stillborns autopsied at 23-40 weeks of gestational age were macroscopically analyzed, and their length and perimeter were measured. Fifty-five tongue fragments were collected through a longitudinal section in the region that accompanies the median lingual sulcus and histologically processed. Slides were stained with picrosirius and immunolabeled with CD31 antibody. Quantification was performed on collagen fibers under polarized light, and on the perimeter of vessels with the CD31. RESULTS: A positive and significant correlation of gestational age with tongue perimeter and length was found. There was a positive and significant correlation between collagen fibers and gestational age, as well as between gestational age and the perimeter of blood vessels. Between collagen fibers and fetal weight, a positive and significant increase was observed. Regarding the correlation between the perimeter of blood vessels and the fetal weight, an increase was observed. CONCLUSION: As gestational age advances, there is an increase in tongue perimeter and length, in the percentage of collagen fibers, and in vascular perimeter, demonstrating that tongue formation is directly related to tongue growth and development.

Sickle cell anemia - Nitric oxide related genetic modifiers of hematological and biochemical parameters.

BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4 VNTR. RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744_TT and the rs1799983_GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR. CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.

Mining gene-centric relationships from literature: the roles of gene mutation and gene expression in supporting drug discovery.

Identifying drug target candidates is an important task for early development throughout the drug discovery process. This process is supported by the development of new high-throughput technologies that enable better understanding of disease mechanism. It becomes critical to facilitate effective analysis of the large amount of biological data. However, with much of the biological knowledge represented in the literature in the form of natural text, analysis and interpretation of high-throughput data has not reached its potential effectiveness. In this paper, we describe our solution in employing text mining as a technique in finding scientific information for target and biomarker discovery from the biomedical literature. Our approach utilises natural language processing techniques to capture linguistic patterns for the extraction of biological knowledge from text. Additionally, we discuss how the extracted knowledge is used for the analysis of biological data such as next-generation sequencing and gene expression data.