Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.

Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82-100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight (ALAD rs1800435, CYP3A4 rs2740574, CYP3A5 rs776746, CYP3A7 rs2257401, GSTP1 rs1695, MT1A rs8052394, MT1M rs2270836, and MT4 rs11643815) and three (MT1A rs8052394, MT1M rs2270837, and MT2A rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The MT1A rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.

Genetic Variations in Susceptibility to Traumatic Muscle Injuries and Muscle Pain among Brazilian High-Performance Athletes.

Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes' performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (ACTN3 rs1815739, FAAH rs324420, PPARGC1A rs8192678, ADRB2 rs1042713, NOS3 rs1799983, and VDR rs731236), none was significantly associated with TMI. Regarding MP after exercise, ACTN3 rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01-3.57) and FAAH rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08-4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of ACTN3 rs1815739 and FAAH rs324420. This could have implications for prophylactic interventions to improve athletes' quality of life.

NUDT15 and TPMT polymorphisms in three distinct native populations of the Brazilian Amazon.

This is the first report of the distribution of TPMT and NUDT15 single nucleotide polymorphisms and metabolic phenotypes associated with cytotoxicity of thiopurine drugs, in indigenous groups of Brazilian Amazon: Munduruku, Paiter-Suruí and Yanomami. The minor allele frequency (MAF) of NUDT15 rs116855232 did not differ significantly across the groups; TPMT rs1800462 was absent, while rs1800460 and rs1142345 were in strong linkage disequilibrium, and 10- and 30-fold more common in Paiter-Suruí. Indeed, the MAFs in Paiter-Surui (0.193 and 0.188) are the largest report globally. The distribution of combined NUDT15/TPMT metabolic phenotypes differed significantly (p < 0.0001) and largely (Cramér´s V = 0.37) across cohorts. This has important pharmacogenetic implications: the Clinical Pharmacogenetics Implementation Consortium recommendations to reduce or consider reduction of thiopurine dose applies to 4.4% Yanomami, 5.6% Munduruku, versus 41% Paiter-Suruí. The proportion of Paiter-Suruí at risk of thiopurine intolerance is 3- to 4-fold higher than any other population worldwide.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Association of polymorphism in leptin receptor gene with susceptibility of adolescent idiopathic scoliosis.

PURPOSE: Abnormal leptin bioavailability has play key roles in the etiology of adolescent idiopathic scoliosis (AIS). Both leptin and its receptor levels may be modulated by the presence of genetic polymorphisms. This study aimed to evaluate the role of polymorphisms in the leptin (LEP) and its main receptor (LEPR) genes in the AIS susceptibility in girls. METHODS: A retrospective case-control study was conducted with 189 AIS and 240 controls. LEP rs2167270 and LEPR rs2767485 polymorphisms were genotyped using a TaqMan validated assay. Associations were evaluated by odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The AIS group showed a predominance of girls under 18 years old (n = 140, 74.1%), 148 (78.3%) had low or normal BMI, 111 (58.7%) had Cobb ≥ 45º and 130 (68.7%) were skeletally mature. Minor allele frequencies of rs2167270 and rs2767485 were 35.7% and 18.3%, for AIS and 35.6% and 25.4% for controls, respectively. LEPR rs2767485 T and TC + TT were associated with higher risk of AIS (OR = 1.53; 95% CI = 1.09-2.13 and OR = 1.84; 95% CI = 1.69-2.01, respectively), since CC genotype was only present in the control group. In addition, the LEP rs2167270 GA + AA was more frequent in low weight group (BMI ≤ 24.9) of girls with AIS. There was no significant association between LEP rs2167270 and AIS susceptibility, and LEPR rs2767485 and BMI. CONCLUSION: The LEPR rs2767485 was associated with the genetic susceptibility of AIS and LEP rs2167270 with low BMI. These data can contribute to the identification of genetic biomarkers to improve the diagnosis and treatment.

Euterpe oleracea extract (açaí) exhibits cardioprotective effects after chemotherapy treatment in a breast cancer model.

BACKGROUND: Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo. METHODS: Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses. RESULTS: Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples. CONCLUSION: Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.

Genetic Polymorphisms in COL1A2 gene and the Risk of Tendinopathy: Case-Control Study.

Objective To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COL1A1 (rs1107946) and COL1A2 (rs412777, rs42524, and rs2621215) were analyzed by the TaqMan system. Odds ratio (OR) with their 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COL1A1 rs1107946 24.0 and 29.6%; COL1A2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COL1A2 rs42524 and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95%CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COL1A2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion Age (≥ 25 years old), time of sports practice (≥ 6 years) and polymorphisms in the COL1A2 gene increased the risk of developing tendinopathy.

Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain.

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis' development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m2) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis' prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29-0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis' painful symptoms, preventing its complications, and allowing an individualized treatment.

Genetic Polymorphisms in COL1A2 gene and the Risk of Tendinopathy: Case-Control Study / Polimorfismos genéticos no gene COL1A2 eo risco de tendinopatia: Estudo de caso-controle

Abstract Objective To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COLIAI (rs1107946) and COLIA2 (rs412777, rs42524, and rs2621215) were analyzed by theTaqMansystem. Odds ratio(OR)withtheir 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COLIAI rs1107946 24.0 and 29.6%; COLIA2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COLIA2 rs42524and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95% CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COLIA2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion Age (≥ 25 years old), time of sports practice (≥ 6years) and polymorphisms in the COLIA2 gene increased the risk of developing tendinopathy.

Resumo Objetivo Avaliar a influência de polimorfismos nos genes que codificam o colágeno tipo I e a suscetibilidade genética da tendinopatia. Metodologia Estudo caso-controle envolvendo 242 atletas brasileiros de diferentes modalidades esportivas (55 casos de tendinopatia e 187 controles). Os polimorfismos COL1A1 (rs1107946) e COL1A2 (rs412777, rs42524 e rs2621215) foram analisados pelo sistema TaqMan. As razões de chance (OR) com seus intervalos de confiança (IC) de 95% foram calculadas usando um modelo de regressão logística não-condicional. Resultados A média de idade foi de 24,0 ± 5,6 anos e 65,3% eram homens. Dos 55 casos de tendinopatia, 25,4% apresentaram mais de um tendão acometido, sendo os maisfrequentesopatelar(56,3%),omanguitorotador(30,9%)eodocotoveloou flexores das mãos (30,9%). A idade e o tempo de prática esportiva foram associados a uma maior chance de apresentar tendinopatia (5 e 8 vezes, respectivamente). A frequência dos alelos variantes nos controles e casos, respectivamente, foi: COL1A1 rs1107946 24,0 e 29,6%; COL1A2 rs412777 36,1 e 27,8%; rs42524 17,5 e 25,9%; e rs2621215 21,3 e 27,8%. Após ajuste pelos fatores de confundimento (idade e anos de práticas esportiva), os polimorfismos COL1A2 rs42524 e rs2621215 foram associados a um risco aumentado de tendinopatia (OR = 5,5; IC95% = 1,2-24,6 e OR = 3,9; IC95% = 1,1-13,5, respectivamente). O haplótipo COL1A2 CGT foi associado a um baixo risco para desenvolvimento da doença (OR = 0,5; IC95% = 0,3-0,9). Conclusão Aidade (> 25 anos), o tempo de prática esportiva (> 6 anos) e polimorfismos no gene COL1A2 aumentaram o risco de desenvolvimento da tendino-patia.

Clotrimazole is effective, safe and tolerable for the treatment of endometriosis and functions by downregulating inducible nitric oxide synthase and modulating oxidative stress biomarkers.

This study investigated the mechanism of action of clotrimazole (CTZ) and its adverse effects in a model of endometriosis. After autologous endometrial implantation, 18 rats were randomized into two treatment groups: 200 mg/kg CTZ or vehicle for 15 consecutive days. The lesion growth, implant size, glandular atrophy, nitric oxide (NO) serum levels, number of macrophage cells and inducible nitric oxide synthase (iNOS) immunoreactivity were significantly reduced in the CTZ group compared with the control. CTZ (p < 0.05) reduced the lipid peroxidation and protein carbonylation levels in the liver but did not alter the superoxide dismutase (SOD), glutathione (GSH) or glutathione S-transferase (GST) levels in the brain; however, the drug significantly reduced SOD activity and enhanced GST activity in the liver. These results suggest that CTZ interferes with reactive nitrogen species production by downregulating iNOS expression and thus enhances the antioxidant system to promote atrophy and regression of endometriotic lesions, without adverse effects on the brain and/or liver.

Chronic Mercury Exposure and GSTP1 Polymorphism in Munduruku Indigenous from Brazilian Amazon.

Genetic polymorphisms may be involved with mercury levels and signs and symptoms of intoxication from this exposure. Therefore, the aims were to describe the frequency of the GSTP1 polymorphism and to evaluate its effects on mercury levels and neurological signs in three Munduruku indigenous villages in the Brazilian Amazon. One-hundred-and-seven indigenous (over 12 years old) were included and genotyped (rs1695) using a TaqMan validated assay. Then, associations were evaluated by binary logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 27.4 ± 13.9 years old, 52.3% were male, mean hair mercury concentration was 8.5 ± 4.3, exceeding the reference limit (≥6.0 µg/g), and were different among the three villages: 13.5 ± 4.6 µg/g in Sawré Aboy, 7.4 ± 2.3 µg/g in Poxo Muybu and 6.9 ± 3.5 µg/g in Sawré Muybu. The minor allele frequency of GSTP1 G was significantly different among the villages: 57% Sawré Muybu, 21% Poxo Muybu and 15% Sawré Aboy. Finally, after adjustment, GSTP1 GG and GA genotypes were associated with lower levels of Hg (OR = 0.13; CI95% = 0.03-0.49) and abnormal somatosensory signs (OR = 3.7; 95%IC = 1.5-9.3), respectively. In conclusion, monitoring this population is imperative to identify individuals at higher risk of developing signs of chronic mercury exposure based on the genetic profile.

Evaluation of cervical lordosis in patients with adolescent idiopathic scoliosis / Avaliação da lordose cervical nos pacientes com escoliose idiopática do adolescente / Evaluación de lordosis cervical en pacientes con escoliosis idiopática del adolescente

ABSTRACT: Introduction: In healthy individuals and in patients with adolescent idiopathic scoliosis (AIS), the curvature of the cervical spine varies greatly, with approximately 36-40% of AIS patients having kyphosis of the cervical spine. Aim: To assess the curvature of the cervical spine in AIS patients and subgroups according to Lenke's classification (1 to 6). Methods: 107 patients with AIS were assessed for cervical lordosis (C2-C7) using the Cobb method, subdivided into lordosis and cervical kyphosis. The following parameters were assessed and compared between the subgroups: T5-T12 thoracic kyphosis (TK); L1-S1 lumbar lordosis (LL), pelvic incidence (PI), sagittal vertical axis (SVA), T1 pelvic angle (TPA), C2-C7 cervical lordosis, C1-C2 cervical lordosis, T1 slope (T1s), neck tilt, thoracic inlet angle (TIA) and cervical sagittal axis (CSVA). Results: Kyphosis of the cervical spine was observed in 48% of patients. The Lenke classification curves (1 to 6) showed no difference with regard to the curvature of the cervical spine. In the subgroup with cervical lordosis, thoracic kyphosis, and T1 slope were significantly higher. Neck tilt was significantly higher in the subgroup with kyphosis. Conclusions: Almost half of the patients have kyphosis of the cervical spine, and the curvature of the cervical spine in AIS patients varies widely. Thoracic kyphosis, T1 slope, and neck tilt are significantly different between the subgroups of patients with lordosis or kyphosis. Level of Evidence III; Observational and Retrospective Study.

RESUMO: Introdução: Nos indivíduos saudáveis e nos pacientes com escoliose idiopática do adolescente (EIA) a curvatura da coluna cervical apresenta grande variação, sendo que aproximadamente 36-40% dos pacientes com EIA apresentam cifose da coluna cervical. Objetivo: Avaliar a curvatura da coluna cervical nos pacientes com EIA e nos subgrupos, de acordo com a classificação de Lenke (1 a 6). Métodos: Foram avaliados 107 pacientes com EIA quanto a lordose cervical (C2-C7), pelo método de Cobb, subdivididos em dois grupos: lordose e cifose cervical. Foram avaliados e comparados entre os subgrupos os seguintes parâmetros: cifose torácica T5-T12 (TK); lordose lombar L1-S1 (LL), incidência pélvica (PI), eixo sagital vertical (SVA), ângulo T1 pélvico (TPA), lordose cervical C2-C7, lordose cervical C1-C2, inclinação T1 (T1s), inclinação cervical (neck tilt), ângulo entrada torácica (TIA) e eixo cervical sagital (CSVA). Resultados: A cifose da coluna cervical foi observada em 48% dos pacientes. As curvas de classificação de Lenke (1 a 6) não apresentaram diferença com relação à curvatura da coluna cervical. No subgrupo com lordose cervical a cifose torácica e a inclinação de T1 foram significativamente maiores. A inclinação cervical foi significativamente maior no subgrupo com cifose. Conclusões: Quase a metade dos pacientes apresenta cifose da coluna cervical, sendo amplamente variável a curvatura da coluna cervical nos pacientes com EIA. A cifose torácica, a inclinação de T1 e a inclinação cervical são significativamente diferentes entre os subgrupos de pacientes com lordose ou cifose. Nível de Evidência III; Estudo Observacional e Retrospectivo.

RESUMEN: Introducción: En individuos sanos y en pacientes con escoliosis idiopática del adolescente (EIA), la curvatura de la columna cervical varía enormemente, y aproximadamente el 36-40% de los pacientes con EIA presentan cifosis de la columna cervical. Objetivo: Evaluar la curvatura de la columna cervical en pacientes con EIA y subgrupos según la clasificación de Lenke (1 a 6). Métodos: Se evaluó la lordosis cervical (C2-C7) de 107 pacientes con EIA mediante el método de Cobb, subdivididos en dos grupos: lordosis y cifosis cervical. Se evaluaron y compararon los siguientes parámetros entre los subgrupos: Cifosis torácica (TK) T5-T12; lordosis lumbar (LL) L1-S1, incidencia pélvica (PI), eje vertical sagital (SVA), ángulo pélvico T1 (TPA), lordosis cervical C2-C7, lordosis cervical C1-C2, inclinación T1 (T1s), inclinación del cuello, ángulo de la entrada torácica (TIA) y eje sagital cervical (CSVA). Resultados: Se observó cifosis de la columna cervical en el 48% de los pacientes. Las curvas de clasificación de Lenke (1 a 6) no mostraron diferencias con respecto a la curvatura de la columna cervical. En el subgrupo con lordosis cervical, la cifosis torácica y la inclinación T1 eran significativamente mayores. La inclinación cervical fue significativamente mayor en el subgrupo con cifosis. Conclusiones: Casi la mitad de los pacientes presentan cifosis de la columna cervical, y la curvatura de la columna cervical en los pacientes con EIA varía ampliamente. La cifosis torácica, la inclinación T1 y la inclinación cervical son significativamente diferentes entre los subgrupos de pacientes con lordosis o cifosis. Nivel de Evidencia: III; Estudio Observacional y Retrospectivo.

Sagittal misalignment in adolescent idiopathic scoliosis / Desalinhamento sagital na escoliose idiopática do adolescente / Mala alineación sagital en la escoliosis idiopática del adolescente

ABSTRACT: Introduction: The correlation between sagittal and coronal parameters in patients with adolescent idiopathic scoliosis (AIS) presents contradictory results and is not fully understood. Objective: To evaluate the sagittal vertical axis (SVA) and its correlation with sagittal parameters and the main curve in patients diagnosed with AIS. Methods: 109 patients with AIS and indications for surgical treatment were evaluated. The correlation of the SVA with sagittal parameters (thoracic kyphosis, lumbar lordosis, pelvic incidence, lumbar lordosis, pelvic version, and sacral inclination) and with the main curves (main thoracic and thoracolumbar/lumbar) was evaluated. Results: The SVA ranged from -208 to 66.30 mm (mean -19.64 ± 36.21), above 50 mm in two patients (1.83%). There was no correlation between the sagittal parameters and the magnitude of the main curve and the SVA. Conclusion: The SVA showed great variability in the group of patients with AIS; a small percentage of patients had an SVA greater than 50 mm. The low percentage of patients with sagittal misalignment showed the compensatory capacity of young patients with vertebral deformity. Level of Evidence: III; Observational and Retrospective Study.

RESUMO: Introdução: A correlação entre os parâmetros sagitais e coronais nos pacientes com escoliose idiopática do adolescente (EIA) apresenta resultados contraditórios e não está totalmente esclarecida. Objetivo: Avaliar o eixo sagital vertical (SVA) e sua correlação com parâmetros sagitais e a curva principal de pacientes com diagnóstico de EIA. Métodos: Foram avaliados 109 pacientes com EIA e indicação de tratamento cirúrgico. Foi avaliada a correlação do SVA com parâmetros sagitais (cifose torácica, lordose lombar, incidência pélvica, lordose lombar, versão pélvica e inclinação do sacro) e com as curvas principais (torácica principal e toracolombar/lombar). Resultados: O SVA variou de -208 a 66,30 mm (média -19,64 ± 36,21), ficando acima de 50 mm em dois pacientes (1,83%). Não foi observada correlação dos parâmetros sagitais e da magnitude da curva principal com o SVA. Conclusão: O SVA apresentou grande variabilidade no grupo de pacientes com EIA e pequena porcentagem dos pacientes apresentaram SVA maior que 50 mm. A baixa porcentagem de pacientes com desalinhamento sagital evidenciou a capacidade compensatória dos pacientes jovens e com deformidade vertebral. Nível de Evidência: III; Estudo Observacional e Retrospectivo.

RESUMEN: Introducción: La correlación entre los parámetros sagitales y coronales en pacientes con escoliosis idiopática del adolescente (EIA) presenta resultados contradictorios y no se comprende completamente. Objetivo: Evaluar el eje vertical sagital (SVA) y su correlación con los parámetros sagitales y la curva principal en pacientes diagnosticados de EIA. Métodos: Se evaluaron 109 pacientes con EIA e indicación de tratamiento quirúrgico. Se evaluó la correlación del SVA con parámetros sagitales (cifosis torácica, lordosis lumbar, incidencia pélvica, lordosis lumbar, versión pélvica e inclinación sacra) y con las curvas principales (torácica principal y toracolumbar/lumbar). Resultados: El SVA osciló entre -208 y 66,30 mm (media -19,64 ± 36,21), siendo superior a 50 mm en dos pacientes (1,83%). No hubo correlación entre los parámetros sagitales o la magnitud de la curva principal y el SVA. Conclusión: El SVA mostró una gran variabilidad en el grupo de pacientes con EIA y un pequeño porcentaje de pacientes presentó una SVA superior a 50 mm. El bajo porcentaje de pacientes con desalineación sagital mostró la capacidad compensatoria de los pacientes jóvenes con deformidad vertebral. Nivel de Evidencia: III; Estudio Observacional y Retrospectivo.

Polymorphisms in paired box 1 gene were associated with susceptibility of adolescent idiopathic scoliosis: A case-control study.

Background: Association of genetic polymorphisms in paired box 1 (PAX-1) gene can influence the development of adolescent idiopathic scoliosis (AIS). PAX-1 is mainly expressed in the region of the vertebral bodies and intervertebral discs, being important for the proper formation of spinal structures. Objectives: The objective of this study was to evaluate the association of polymorphisms in PAX-1 gene with the susceptibility of AIS. Settings and Design: This was an analytical observational case-control study. Materials and Methods: Samples of 59 AIS indicated for surgical treatment, and 119 controls, without spinal disease were genotyped for PAX-1 rs6137473 and rs169311 polymorphisms. Statistical Analysis: The association of the polymorphisms with AIS was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). Results: According to Lenke's classification, 89.8% had Type I and 10.2% II curves. The mean value of the Cobb angle of the proximal thoracic curve was 30.8°, 58.7° thoracic, and 30.4° for the lumbar and on the bending films 14.6°, 40.7°, and 11°, respectively. Among the AIS group, there was a predominance of females (8.8:1). The PAX-1 rs169311 and rs6137473 polymorphisms were positively associated with developing the AIS (OR = 1.98; 95% CI = 1.2-3.3 and OR = 3.16; 95% CI = 1.4-7.3, respectively). The rs6137473 polymorphism was associated with the lumbar modifier B and C compared to A (OR = 2.52; 95% CI = 1.1-5.8). Conclusions: PAX-1 polymorphisms were associated with an increased risk of developing the AIS and with curve severity and can be used as a biomarker to map the risk of developing surgical-grade AIS, guiding the treatment of patients.

Factors associated with mortality, length of hospital stay and diagnosis of COVID-19: Data from a field hospital.

BACKGROUND: During the pandemic of COVID-19, phylogenetic changes have been observed in the characteristics of the virus, in the diagnosis and treatment of the disease. The clinical course and the severe form of the disease depends on several factors. This study characterized the beginning setting for patient care of COVID-19 in a referral center in one of the main capital cities of Brazil. In addition, were evaluated the factors associated with mortality, length of stay, and diagnostic outcome. METHODS: A cross-sectional study was conducted during May 2020 (n = 1100). The association of the variables with outcome was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95 % confidence intervals (CI). RESULTS: Overall, 76 % of patients were COVID-19 positive, and 70 % were diagnosed by RT-qPCR. The majority were male (56 %), and over 52 years old (74 %), 68 % had hypertension, 44 % had diabetes mellitus, and 32 % were obese. The mean length of stay was 10 ± 8 days, which was higher in the 34 % who died (≥14; OR=2; 95 %CI=1.4-4) and who had hypertension (OR=2; 95 %CI=1.3-3) (P < 0.001). The mean length of stay was also higher (P = 0.008) for those patients with pulmonary impairment ≥ 50 % (10.72 ± 8.24), than those with< 50 % (8.98 ± 6.81). Age (>62 and 65 years) was associated with longer hospitalization (OR=2; 95 %CI=1.4-3) and death (OR=6; 95 %CI=3-11). The time of sample collection for RT-qPCR was different between positive and negative tests (P = 0.001), with the time of 4-10 days showing a greater chance for virus detection (OR=2.9; 95 %CI=1.6-5). CONCLUSION: Death was associated with age and pulmonary impairment. The length of hospitalization was associated with age, hypertension, pulmonary impairment and death. The time of sample collection to perform RT-qPCR and the rapid test was associated with a positive result for COVID-19. These results highlight the ongoing challenge of diagnosing, treating, and mitigating the effects caused by the COVID-19 pandemic.

Association of FBN1 polymorphism with susceptibility of adolescent idiopathic scoliosis: a case-control study.

BACKGROUND: Fibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient's characteristics. METHODS: DNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient's age and body mass index (BMI). RESULTS: Among the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35-0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°). CONCLUSION: Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

Influence of type I collagen polymorphisms and risk of anterior cruciate ligament rupture in athletes: a case-control study.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common and severe knee injury in sports and occurs mostly due to noncontact injuries. There is an increasing amount of evidence associating ACL rupture to single nucleotide polymorphisms (SNPs), and SNPs in the collagen type I genes can change its expression and tissue mechanical features. This study aimed to investigate the association between SNPs in COL1A1 and COL1A2 with sports-related ACL tears. METHODS: A total of 338 athletes from multiple sports modalities were analyzed: 146 were diagnosed with ACL rupture or underwent an ACL reconstruction surgery and 192 have no musculoskeletal injuries. SNPs were genotyped using validated TaqMan assays. The association of the polymorphisms with ACL rupture was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The age, sport modality, and training location were associated with an increased risk of a non-contact ACL tear. COL1A2 SNPs (rs42524 CC and rs2621215 GG) were associated with an increased risk of non-contact ACL injury (6 and 4-fold, respectively). However, no significant differences were detected in the distribution of COL1A1 rs1107946 and COL1A2 rs412777 SNPs between cases and controls. There was a protective association with ACL rupture (OR = 0.25; 95% CI = 0.07-0.96) between COL1A1 rs1107946 (GT or TT) and the wildtype genotypes of the three COL1A2 (rs412777, rs42524, rs2621215). COL1A2 rs42524 and rs2621215 SNPs were associated with non-contact ACL risk. CONCLUSION: The combined analysis of COL1A1-COL1A2 genotypes suggests a gene-gene interaction in ACL rupture susceptibility.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 µg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.