Genetic variation in NOTCH1 is associated with overweight and obesity in Brazilian elderly.

Excessive weight (overweight and obesity) is a common disorder involving genetic and environmental factors, associated with cardiovascular diseases, type-2 diabetes, and others. NOTCH1 is critical for the maintenance of stem cells and adult tissues, being reported as a key player in metabolism and adipogenesis in animals. Thus, we test the hypothesis that NOTCH1 Single Nucleotide Polymorphisms (SNPs) are associated with excessive weight. Participants from the census-based cohort SABE (Saúde, Bem Estar e Envelhecimento-Health, Well-Being, and Aging), carried out in the city of São Paulo-Brazil, were stratified into cases and controls according to BMI. We filter the SNPs located at the start and end positions of NOTCH1 and 50 Kb on both sides. We selected SNPs with minor allelic frequency (MAF) greater than or equal to 0.01 and Hardy-Weinberg equilibrium (p > 0.05) and r2 ≥ 0.8. We performed an association study with genotypes and haplotypes, as well as in silico functional analysis of the identified SNPs. We observed an association of the SNP rs9411207 with the risk of excessive weight, under log-additive model, and the genotype distribution showed an increased frequency of homozygous TT (OR 1.50, CI 1.20-1.88; p = 0.0002). The haplotype GAT constructed from this and other SNPs in high Linkage Disequilibrium was more frequent in excessive-weight individuals (p = 0.003). In silico analyses suggested that these SNPs are likely to affect the transcription of NOTCH1 and other genes involved in adipogenesis and metabolism. This is the first study reporting association between NOTCH1 SNPs and the risk of excessive weight. Considering the possibility of NOTCH1 modulation, additional population studies are important to replicate these data and confirm the usefulness of risk genotypes for management strategies of excessive weight.

Validating GWAS Variants from Microglial Genes Implicated in Alzheimer's Disease.

Late-onset Alzheimer's disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer's disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aß peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aß peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.

Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault.

Micronucleus test in peripheral blood of rats treated with hyperbaric oxygen after subtotal splenectomy preserving the lower pole.

PURPOSE: To assess the mutagenic potential of the oxygen inhalation therapy (HBO), by means of the micronucleus test, performed in peripheral blood of rats that underwent subtotal splenectomy with lower pole preservation (ESTPI), after HBO sessions or simulations. METHODS: Eighteen male Wistar rats, were distributed into three groups of six animals: group 1 - submitted to ESTPI and HBO sessions; group 2 - submitted to ESTPI and HBO simulations; group 3 - underwent cyclophosphamide administration. In groups 1 and 2, blood samples from the animals' tails were collected before surgery (T0) and immediately after the 13th HBO session or simulation (T1). In group 3, tail blood samples were collected from animals before (T0) and 24 hours after (T1) cyclophosphamide (CP) delivery. The number of micronucleated normochromatic erythrocytes (MNNCE) was determined by blind counting 2000 normochromatic erythrocytes (NCE) per animal. RESULTS: Micronuclei average after CP delivery in group 3 was higher than before its use, thus confirming the mutagenic activity of this drug (p=0.01). In groups 1 and 2, no significant difference in the average of Micronuclei was observed when comparing it to blood samples before and after the 13th HBO session or simulation. CONCLUSION: The treatment protocol used in this study did not induce Micronucleus formation in animals submitted to ESTPI and HBO treatment or simulation.

Micronucleus test in peripheral blood of rats treated with hyperbaric oxygen after subtotal splenectomy preserving the lower pole

PURPOSE: To assess the mutagenic potential of the oxygen inhalation therapy (HBO), by means of the micronucleus test, performed in peripheral blood of rats that underwent subtotal splenectomy with lower pole preservation (ESTPI), after HBO sessions or simulations. METHODS: Eighteen male Wistar rats, were distributed into three groups of six animals: group 1 - submitted to ESTPI and HBO sessions; group 2 - submitted to ESTPI and HBO simulations; group 3 - underwent cyclophosphamide administration. In groups 1 and 2, blood samples from the animals' tails were collected before surgery (T0) and immediately after the 13th HBO session or simulation (T1). In group 3, tail blood samples were collected from animals before (T0) and 24 hours after (T1) cyclophosphamide (CP) delivery. The number of micronucleated normochromatic erythrocytes (MNNCE) was determined by blind counting 2000 normochromatic erythrocytes (NCE) per animal. RESULTS: Micronuclei average after CP delivery in group 3 was higher than before its use, thus confirming the mutagenic activity of this drug (p=0.01). In groups 1 and 2, no significant difference in the average of Micronuclei was observed when comparing it to blood samples before and after the 13th HBO session or simulation. CONCLUSION: The treatment protocol used in this study did not induce Micronucleus formation in animals submitted to ESTPI and HBO treatment or simulation. .

Immunoexpression of proliferating cell nuclear antigen (PCNA) in spleen of splenectomized rats with preservation of inferior pole, submitted to hyperbaric oxygenation.

PURPOSE: To analyze PCNA immunoexpression on the inferior pole of the spleen of splenectomized rats submitted to hyperbaric oxygenation (HBO). METHODS: Were analyzed fragments of the inferior pole of the spleen of 20 male Wistar rats submitted to splenectomy with preservation of the inferior pole. The rats were divided in two groups: group A (n=10) without HBO and group B (n=10) submitted to HBO at 2, 5 atmospheres per 120 minutes, twice a day for three days and once a day for seven days. The groups were then subdivided in four subgroups: A15 (n=5), with euthanasia on the 15th day; A45 (n=5), with euthanasia on the 45th day; B15 (n=5) with euthanasia on the 15th day and B45 with euthanasia on the 45th day. Respectively on these days, fragments of the inferior pole of the spleen of all animals were collected and analyzed with the immunohistochemistry technique in order to evaluate PCNA expression. RESULTS: There was an expressive increase in PCNA immunoreactivity in the group B. The 45 day postoperative period resulted in a higher level of positivity than the 15 day postoperative period (p<0.01). CONCLUSION: The quantitative analysis of proliferating cell nuclear antigen positive suggests that hyperbaric oxygenation increases cellular proliferation, contributing to splenic regeneration.

Immunoexpression of proliferating cell nuclear antigen (PCNA) in spleen of splenectomized rats with preservation of inferior pole, submitted to hyperbaric oxygenation

PURPOSE: To analyze PCNA immunoexpression on the inferior pole of the spleen of splenectomized rats submitted to hyperbaric oxygenation (HBO). METHODS: Were analyzed fragments of the inferior pole of the spleen of 20 male Wistar rats submitted to splenectomy with preservation of the inferior pole. The rats were divided in two groups: group A (n=10) without HBO and group B (n=10) submitted to HBO at 2, 5 atmospheres per 120 minutes, twice a day for three days and once a day for seven days. The groups were then subdivided in four subgroups: A15 (n=5), with euthanasia on the 15th day; A45 (n=5), with euthanasia on the 45th day; B15 (n=5) with euthanasia on the 15th day and B45 with euthanasia on the 45th day. Respectively on these days, fragments of the inferior pole of the spleen of all animals were collected and analyzed with the immunohistochemistry technique in order to evaluate PCNA expression. RESULTS: There was an expressive increase in PCNA immunoreactivity in the group B. The 45 day postoperative period resulted in a higher level of positivity than the 15 day postoperative period (p<0.01). CONCLUSION: The quantitative analysis of proliferating cell nuclear antigen positive suggests that hyperbaric oxygenation increases cellular proliferation, contributing to splenic regeneration.

Gastric bypass and sleeve gastrectomy: the same impact on IL-6 and TNF-α. Prospective clinical trial.

BACKGROUND: Due to the association between the quantity of adipose tissue and concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), this work aimed to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures on serum IL-6 and TNF-α concentrations. METHODS: This study evaluated serum IL-6 and TNF-α levels, as well as routine anthropometric and biochemical values, before and 1 year post-bariatric surgery. Fifty percent of patients (n = 24) underwent RYGB, and 50 % (n = 24) underwent SG. Prior to bariatric surgery, IL-6 and TNF-α mRNA expression levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were investigated in obese women. RESULTS: There was a significant reduction (p < 0.05) in all anthropometric and routine biochemical measurements in patients in the RYGB and SG groups 1 year post-surgery. The serum concentrations of IL-6 and TNF-α were reduced following surgery in both groups (p < 0.05). No differences in the relative expression levels of IL-6 and TNF-α were found between SAT and VAT prior to bariatric surgery. CONCLUSIONS: RYGB and SG procedures demonstrated a similar impact on adipokine levels in women 1 year post-surgery. Both techniques may improve the course of chronic diseases and the state of inflammation associated with obesity.

Protocolo de pesquisa: o desafio do aprimoramento ético / Research protocol: the challenge of ethical improvement

O trabalho analisa protocolos de pesquisas no âmbito universitário submetidos nos últimos três anos ao Comitê de Ética em Pesquisa da Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória (CEP/Emescam). Este CEP avalia 200 projetos/ano. Os dados foram restritos ao título dos projetos e número de sujeitos. Os achados foram agrupados conforme a Biblioteca Virtual de Saúde (BVS). As pesquisas concentram-se nas categorias saúde do trabalhador; aleitamento materno, saúde materna e da mulher; adolescência, criança e idoso. Economia, indicadores de saúde, alta complexidade e ciência e tecnologia estão ausentes. Considerando que a preferência pela área temática advém da familiaridade com o tema, os dados levantados foram comparados com a experiência dos pesquisadores, registrada na Plataforma Lattes. Sabe-se que hoje as pesquisas são resultado dos esforços passados dos pesquisadores e conhecer o cenário atual da pesquisa acadêmica é importante para planejar o futuro da pesquisa em saúde no país.