Substantial incidence of bladder dysfunction in patients with VACTERL association: Implications for surveillance.

VACTERL association is defined as the nonrandom co-occurrence of a minimum of three of the following six key components: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Patients presenting with two components may also belong in the same spectrum. Additional components have been associated with VACTERL defects, including single umbilical artery, tethered spinal cord (TSC), and genital malformations. We observed a significant proportion of patients with bladder dysfunction (often called neurogenic bladder in the medical record) when reviewing a cohort of patients with VACTERL defects at our clinical center. Our finding calls attention to bladder dysfunction as an additional VACTERL phenotypic component. The prevalence of bladder dysfunction is greatest in those with genital anomalies, anorectal malformations, sacral dysplasia, renal anomalies, and TSC. We propose that patients with two or more VACTERL malformations be monitored for symptoms of bladder dysfunction if one or more of the identified risk factors are present until the achievement of urinary continence.

Biochemical changes and bioaccumulation of manganese in Astyanax lacustris (Teleostei: Characidae).

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work.

This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

Histomorphometric evaluation of different graft associations for maxillary sinus elevation in wide antral cavities: a randomized controlled clinical trial.

OBJECTIVES: Pneumatization of the maxillary sinus can make it difficult, if not impossible, to install osseointegrated implants, and undertake their eventual functional rehabilitation, which may ultimately require regenerative techniques to achieve. This randomized controlled study proposed conducting a histological evaluation of the behavior of different graft materials in wide maxillary sinuses, at a height of 8 to 10 mm from the alveolar ridge, combined with bone remnants less than 3mm. MATERIALS AND METHODS: Thirty-six patients underwent a sinus elevation procedure through the lateral window. The sinuses were randomly filled with the following materials (n=12/group): group 1, xenogenic bone + autogenous bone (ratio 70:30, respectively); group 2, xenogenic bone + L-PRF; and group 3, xenogenic bone. At 8 months, bone biopsies of engrafted sites were harvested and analyzed histomorphometrically in order to quantify newly formed bone tissue. RESULTS: The results showed a greater area of newly formed bone for G1, averaging 2678.37 (1116.40) µm2, compared with G2 at 984.87 (784.27) µm2, and G3 at 480.66 (384.76) µm2 (p < 0.05). Additionally, fewer xenogenic bone particles and a large amount of connective tissue were observed in G2. CONCLUSIONS: In maxillary sinuses with large antral cavities, autogenous bone combined with xenogenic bone seems to demonstrate better graft remodeling and improve bone formation, compared with the addition of L-PRF. CLINICAL RELEVANCE: L-PRF produces few advantages regarding new bone formation in the wide maxillary sinuses. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC) number RBR-2pbbrvg.

Advances in tobacco control in the Region of the Americas, 2020.

This report describes the current status of the tobacco control measures contained in the Strategy and Plan of Action to Strengthen Tobacco Control in the Region of the Americas 2018-2022 (Pan American Health Organization) and the advances made in its application, identifying achievements from 2016 to 2020 and challenges that still need to be addressed in order to reach the expected goals. This analysis relied on data from the World Health Organization (WHO) Report on the Global Tobacco Epidemic from 2015, 2017, and 2019, and national regulations were analyzed to determine their consistency with WHO criteria. Significant progress has been made in implementation of the WHO Framework Convention on Tobacco Control in the Americas. By 2020, most countries had regulations on 100% smoke-free environments in indoor public places, workplaces, and public transport, and large graphic health warnings on tobacco packaging. The number of countries that ban tobacco advertising, promotion, and sponsorship and that tax tobacco at the minimum level recommended by WHO has doubled since 2016. However, the 2022 targets have not yet been reached for any of these measures or for ratification of the relevant international agreements. Although progress has been made in the Region, it has not been uniform. Unless the pace of application of the tobacco control measures contained in the Strategy and Plan of Action accelerates, it is unlikely that its targets will be met. Tobacco industry interference remains one of the main challenges.

Se describe el estado actual y los avances en la aplicación de las medidas de control del tabaco contenidas en la Estrategia y Plan de Acción para Fortalecer el Control del Tabaco en la Región de las Américas 2018-2022 y se identifican los logros alcanzados entre los años 2016 y 2020 y los retos que aún se deben enfrentar para cumplir las metas previstas. Para ello se utilizaron los datos del Informe de la Organización Mundial de la Salud (OMS) sobre la Epidemia Mundial de Tabaquismo de los años 2015, 2017 y 2019, así como las normativas nacionales para determinar su consistencia con los criterios de la OMS. Se constatan importantes avances en la aplicación del Convenio Marco de la OMS para el Control del Tabaco en las Américas. Al 2020, la mayoría de los países contaban con normativas sobre ambientes 100% libres de humo en lugares cerrados públicos y de trabajo, y el transporte público, y advertencias sanitarias gráficas grandes en los paquetes de tabaco. Desde el 2016 se duplicó el número de países que prohíben la publicidad, la promoción y el patrocinio del tabaco y que aplican impuestos al tabaco al nivel mínimo recomendado por la OMS. Sin embargo, aún no se ha alcanzado la meta prevista al 2022 para ninguna de esas medidas ni para la ratificación de los tratados internacionales en el tema. Aunque se ha avanzado en la Región, el avance no ha sido uniforme, y a menos que el ritmo de aplicación de las medidas de control del tabaco contenidas en la Estrategia y Plan de Acción se acelere, es poco probable que se logren las metas establecidas. La interferencia de la industria tabacalera se mantiene como uno de los principales retos.

Este artigo descreve a situação atual e o progresso na implementação das medidas para o controle do tabagismo prescritas na Estratégia e plano de ação para fortalecer o controle do tabagismo na Região das Américas 2018-2022, reconhece as conquistas realizadas no período entre 2016 e 2020, e identifica os desafios a serem enfrentados para alcançar as metas planejadas. A análise se baseou em dados obtidos do Relatório da OMS sobre a Epidemia Global do Tabaco, publicado em 2015, 2017 e 2019, e em regulamentações nacionais para determinar o cumprimento dos critérios da OMS. Observam-se avanços na implementação da Convenção-Quadro da OMS para o Controle do Tabaco nas Américas. Em 2020, a maior parte dos países dispunha de regulamentações para ambientes 100% livres da fumaça do tabaco em locais públicos fechados, locais fechados de trabalho e meios de transporte público, e advertências sanitárias com ilustrações gráficas grandes nas embalagens dos produtos de tabaco. O número de países que proíbem publicidade, promoção e patrocínio do tabaco e adotaram impostos sobre os produtos do tabaco no padrão mínimo recomendado pela OMS dobrou desde 2016. No entanto, as metas planejadas para 2022 ainda não foram atingidas ­ tanto em relação a estas medidas quanto à ratificação dos respectivos tratados internacionais. Apesar dos avanços, o progresso na Região não é uniforme. Se as medidas para o controle do tabaco prescritas na Estratégia e plano de ação não forem implementadas em um ritmo acelerado, as metas dificilmente serão alcançadas. A interferência da indústria do tabaco continua sendo um dos maiores desafios.

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments.

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

Amaryllidaceae-Type Alkaloids from Pancratium maritimum: Apoptosis-Inducing Effect and Cell Cycle Arrest on Triple-Negative Breast Cancer Cells.

Aiming to find Amaryllidaceae alkaloids against breast cancer, including the highly aggressive triple-negative breast cancer, the phytochemical study of Pancratium maritimum was carried out. Several Amaryllidaceae-type alkaloids, bearing scaffolds of the haemanthamine-, homolycorine-, lycorine-, galanthamine-, and tazettine-type were isolated (3-11), along with one alkamide (2) and a phenolic compound (1). The antiproliferative effect of compounds (1-11) was evaluated by the sulforhodamine B assay against triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, breast cancer cells MCF-7, and the non-malignant fibroblast (HFF-1) and breast (MCF12A) cell lines. The alkaloids 3, 5, 7, and 11 showed significant growth inhibitory effects against all breast cancer cell lines, with IC50 (half-maximal inhibitory concentration) values ranging from 0.73 to 16.3 µM. The homolycorine-type alkaloid 7 was selected for further investigation in MDA-MB-231 cells. In the annexin-V assay, compound 7 increased cell death by apoptosis, which was substantiated, in western blot analyses, by the increased expression of the pro-apoptotic protein Bax, and the decreased expression of the anti-apoptotic protein Bcl-xL. Consistently, it further stimulated mitochondrial reactive oxygen species (ROS) generation. The antiproliferative effect of compound 7 was also associated with G2/M cell cycle arrest, which was supported by an increase in the p21 protein expression levels. In MDA-MB-231 cells, compound 7 also exhibited synergistic effects with conventional chemotherapeutic drugs such as etoposide.

Do Manganese and Iron in Association Cause Biochemical and Genotoxic Changes in Oreochromis Niloticus (Teleostei: Cichlidae)?

The present study aimed to evaluate the toxicity of the association between Fe and Mn in Oreochromis niloticus through genotoxic (micronucleus test and comet assay) and biochemical (CAT and GST enzymes) assays. The tested treatments were T1 = control group (without metal addition), T2 = 2.60 mg L-1 of Fe + 0.2 mg L-1 of Mn, and T3 = 4.40 mg L-1 of Fe + 3.49 mg L-1 of Mn, during 96-h bioassays. All animals exposed to the metals showed a significant increase in erythrocyte micronucleus frequency and DNA damage. The hepatic GST activity increased two times in animals exposed to T3 compared to the control group. The results indicate that Fe + Mn caused genotoxic and biochemical changes in exposed fish. Therefore, excess metals in ecosystems, even those essential for organisms, can be dangerous for the local biota due to the risk associated with high concentrations of these metals.

Metal bioaccumulation and its genotoxic effects on eggs and hatchlings of giant Amazon river turtle (Podocnemis expansa).

The aim of this study was to assess whether possible metal contamination in the sediment of the nests of giant Amazon river turtle, Podocnemis expansa, could contaminate eggs and hatchlings, triggering genotoxic damage. Therefore, sediments of P. expansa nests from two sites in the Brazilian Amazon were evaluated, with the first being collected at Araguaia River and the second at Crixás-Açu River. Newly hatched offspring, eggs, and sediments were collected from the beaches of these two rivers and the quantification of metals (Al, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn) was carried out by atomic absorption spectroscopy. All targeted metals were found in both sediment and P. expansa biological samples collected on the beaches presenting higher concentrations in the sediment of Crixás-Açu River. Metals found in the eggshells before nesting and in the egg contents were maternally transferred. Moreover, augmented concentration of metals led by metal transfer from the nests sediments were detected in the eggshells after nesting (ENH) and in the newly hatched offspring (H). Probably this metal relocation to the newly hatchlings augmented the frequency of micronuclei in their blood, presenting 15.25‰ in hatchling found in Crixás-Açu River beaches and 10‰ in newly hatched animals from Araguaia River beaches. These results indicate the occurrence of maternal transfer of metals (essential or not) to the eggs in testudines as well as a transference from the sediments to the nesting eggs, triggering genotoxic effects on the hatchlings.

[Advances in tobacco control in the Region of the Americas, 2020Avanços no controle do tabagismo na Região das Américas 2020]. / Avances en el control del tabaco en la Región de las Américas 2020.

This report describes the current status of the tobacco control measures contained in the Strategy and Plan of Action to Strengthen Tobacco Control in the Region of the Americas 2018-2022 (Pan American Health Organization) and the advances made in its application, identifying achievements from 2016 to 2020 and challenges that still need to be addressed in order to reach the expected goals. This analysis relied on data from the World Health Organization (WHO) Report on the Global Tobacco Epidemic from 2015, 2017, and 2019, and national regulations were analyzed to determine their consistency with WHO criteria. Significant progress has been made in implementation of the WHO Framework Convention on Tobacco Control in the Americas. By 2020, most countries had regulations on 100% smoke-free environments in indoor public places, workplaces, and public transport, and large graphic health warnings on tobacco packaging. The number of countries that ban tobacco advertising, promotion, and sponsorship and that tax tobacco at the minimum level recommended by WHO has doubled since 2016. However, the 2022 targets have not yet been reached for any of these measures or for ratification of the relevant international agreements. Although progress has been made in the Region, it has not been uniform. Unless the pace of application of the tobacco control measures contained in the Strategy and Plan of Action accelerates, it is unlikely that its targets will be met. Tobacco industry interference remains one of the main challenges.

Este artigo descreve a situação atual e o progresso na implementação das medidas para o controle do tabagismo prescritas na Estratégia e plano de ação para fortalecer o controle do tabagismo na Região das Américas 2018-2022, reconhece as conquistas realizadas no período entre 2016 e 2020, e identifica os desafios a serem enfrentados para alcançar as metas planejadas. A análise se baseou em dados obtidos do Relatório da OMS sobre a Epidemia Global do Tabaco, publicado em 2015, 2017 e 2019, e em regulamentações nacionais para determinar o cumprimento dos critérios da OMS. Observam-se avanços na implementação da Convenção-Quadro da OMS para o Controle do Tabaco nas Américas. Em 2020, a maior parte dos países dispunha de regulamentações para ambientes 100% livres da fumaça do tabaco em locais públicos fechados, locais fechados de trabalho e meios de transporte público, e advertências sanitárias com ilustrações gráficas grandes nas embalagens dos produtos de tabaco. O número de países que proíbem publicidade, promoção e patrocínio do tabaco e adotaram impostos sobre os produtos do tabaco no padrão mínimo recomendado pela OMS dobrou desde 2016. No entanto, as metas planejadas para 2022 ainda não foram atingidas ­ tanto em relação a estas medidas quanto à ratificação dos respectivos tratados internacionais. Apesar dos avanços, o progresso na Região não é uniforme. Se as medidas para o controle do tabaco prescritas na Estratégia e plano de ação não forem implementadas em um ritmo acelerado, as metas dificilmente serão alcançadas. A interferência da indústria do tabaco continua sendo um dos maiores desafios.

Impact on Fertility Rate and Embryo-Larval Development Due to the Association Acidification, Ocean Warming and Lead Contamination of a Sea Urchin Echinometra lucunter (Echinodermata: Echinoidea).

Ocean warming and acidification can cause deleterious effects on marine biota, which may be potentialized when associated with metal pollution. Thus, the aim of this work was to evaluate the effects of pH decrease, temperature increase and lead contamination on fertility rate and embryo-larval development of Echinometra lucunter. Gametes and embryos were exposed at pH 8.2 (control) and 7.5; at 26°C (control) and 28°C; and at lead concentrations of 0 (control), 125, 250 and 500 µg/L. These conditions were tested individually and in combination. The fertilization rate of E. lucunter was only significantly reduced in the treatments where temperature was increased and in the treatment where pH decreased. However, the development rate of the pluteus larvae was significantly affected in the majority of treatments: metal contamination in the higher concentration; decreased pH in all metal concentrations; increased temperature in the highest metal concentration; decreased pH and increased temperature and all variables combined, which is decreased pH, increased temperature and metal contamination in relation to the control group (C). The development test was shown to be more sensitive than the fertilization test in all the studied scenarios. In general, the present study suggests that pH decrease, temperature increase and metal pollution may have a significant impact on E. lucunter reproductive cycle.

oipA "on" status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil.

BACKGROUND: Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA "on" status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer. METHODS: We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR. RESULTS: Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA "on" status (OR = 9.20; 95%CI = 1.45-58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03-1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA "on" status (OR = 14.75; 95%CI: 2.53-86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA "on" status did not differ between children and adults (P = 0.87). The oipA "on" status was significantly correlated with the presence of cagA and vacA s1 m1. CONCLUSION: oipA "on" status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.

The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients. METHODS: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations. RESULTS: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype. CONCLUSION: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients.

The Impact of Sublethal Concentrations of Treated Leachate on Nile tilápia (Oreochromis niloticus).

The objective of this study was to evaluate the impact of sublethal concentrations of treated landfill leachate on Oreochromis niloticus individuals after exposure for 96 h, by assessing biochemical, genotoxic and immunologic biomarkers. Among biochemical biomarkers (activities of ALT, AST and GST enzymes), the treated landfill leachate did not cause significant alterations on O. niloticus and did not significantly affect leukocytes used as an immunologic biomarker. On the other hand, treated leachate induced genotoxic damages, since an increase in erythrocytic micronuclei and in DNA damage (comet assay) were observed in fish exposed to all treatment (2, 4 and 6 mL L-1). Acute toxicity of treated leachate in O. niloticus caused only genotoxic changes in blood cells, showing that micronuclei and comet assay, together, are effective biomarkers in determining the acute toxicity of treated leachate in aquatic environments. This work also shows that leachate, although treated, caused some damages to O. niloticus, which indicates the employed treatment was not efficient in eliminating all genotoxic substances from the leachate.

Genotoxic Damages and Bioaccumulation of Cadmium in Geophagus Brasiliensis (Quoy & Gaimard, 1824).

The toxic effects of cadmium (Cd) in Geophagus brasiliensis was investigated in the present study. For this, 32 specimens of G. brasiliensis were exposed in individual aquaria to Cd concentrations (0.00, 0.01, 0.07, and 0.67 mg/L) for 14 days. The micronuclei test did not detect the genotoxic damage at the studied concentrations and time of exposure. However, the comet assay proved to be more efficient, as DNA damage was found in the animals exposed to the higher Cd concentrations. Finally, exposure of G. brasiliensis to Cd was associated with Cd accumulation in the gills, while only the animals exposed to 0.67 mg/L of Cd exhibited muscle accumulation. These results demonstrate that Cd concentrations over 0.07 mg/L caused genotoxic damage, as well as Cd accumulation in G. brasiliensis individuals after a 14 days exposure.

Acute coronary syndrome: Relationship between genetic variants and TIMI risk.

Acute Coronary Syndrome (ACS) is a multifactorial disease, including the genetic factor, caused by coronary artery obstruction by atheroma. Some genetic variants have been described as risk factors for this disease. Its early diagnosis and stratification of risk of death by Thrombolysis in Myocardial Infarction (TIMI) are important. Therefore, we evaluated variants in the IL6R (c950-1722C>T), TNFa (c.-488G>A), LEPR (c.2673+1118C>T) and IL1b (c.-598T>C) genes in relation to TIMI risk, cytokine serum levels, and risk factors for ACS. We selected 200 patients with ACS, 50 without ACS from the Real Hospital Português, Recife - PE, and 295 blood donors at the Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope). Variants were determined by DNA sequencing or enzymatic cleavage. Cytokine levels were measured by ELISA. The most frequent risk factors found in the patients were dyslipidemia and hypertension, this latter associated with high TIMI risk (p = 0.003). Genotype frequencies of IL6R and TNFa differed between patients with ACS and the blood donors (p = 0.0002 and p = 0.01, respectively), and TNF-α levels differed between genotypes. The TT genotype of the IL6R gene is as a possible protective factor for ACS because it was significantly more present in blood donors (32.2%) than in patients with ACS (18.0%), and was more frequent in low TIMI risk (22.9%) than in the intermediate (20.2%) or high (4.9%). In patients with ACS, the TT genotype in IL6R was related to a lower concentration of c-reactive protein (p = 0.03) and troponin (p = 0.02), showing a less inflammatory reaction and tissue damage. The differences in the frequencies of variants in genes of medical interest among the groups show the importance of studies in specific populations groups to establish the relationship between genes and diseases.

Effects of the water-soluble fraction of diesel oil (WSD) on the fertilization and development of a sea urchin (Echinometra lucunter).

Considering the high number of accidents with diesel oil spills occurring in the marine ecosystem, toxicity tests aimed at assessing the effects of this pollutant on biota are necessary and urgent. Thus, the present study aimed to evaluate the toxicity of the soluble fraction of diesel oil (WSD) in the fertilization success of gametes and pluteu larvae of the sea urchin Echinometra lucunter. To do this, gametes and embryos were exposed to concentrations of 0% (control group), 0.5%, 1.5% and 2.5% of WSD. The fertilization success of exposed gametes and embryos were reduced significantly when compared to the control group in all tested concentrations. With this finding, it is evident that diesel oil can be significantly promoted in the early and adult life stages of a particular organism, and a better way of evaluating this toxicity is through the analysis of contaminant effects throughout the reproductive cycle of a species.

Genotoxic, biochemical and bioconcentration effects of manganese on Oreochromis niloticus (Cichlidae).

Manganese and iron were found at high concentrations (3.61 mg/L and 19.8 mg/L, respectively) in the water of the Rio Doce after the dams of Fundão and Santarém broke in Mariana/MG (Brazil). These same metals were found in fish and crustacean muscle (15 mg/kg and 8 mg/kg wet weight, respectively) in the specimens collected near the Rio Doce's outfall. Due to the variation in Mn concentration found in the lower Rio Doce, this study aimed to determine the effects of Mn in Oreochromis niloticus, at the concentrations allowed by CONAMA, and in concentrations found in the Rio Doce after the dams broke. The animals were exposed to the following dissolved concentrations: control group (0.0 mg/L), 0.2; 1.5 and 2.9 mg/L manganese for 96 h. In addition, a positive control was conducted, injecting intraperitoneally with cyclophosphamide (at 25 mg/kg). These exposures caused significant erythrocyte micronucleus formation in the organisms exposed to the highest concentration, as well a significant increase in the DNA damage index of erythrocytes from organisms exposed to 1.5 mg/L and 2.9 mg/L treatments. The glutathione S-transferase enzyme activity also showed a significant increase in the liver of the organisms exposed to 2.9 mg/L. However, catalase activity increased significantly in the gills of the animals exposed to all concentrations of manganese that were tested. Manganese bioconcentrated in greater quantities in the liver than the gills. Thus, manganese causes significant damage to genetic material, generates nuclear abnormalities, activates the body's detoxification system and can accumulate in animal tissue.

Water-soluble fraction of petroleum induces genotoxicity and morphological effects in fat snook (Centropomus parallelus).

Petroleum hydrocarbons are one of the primary organic chemicals found in water bodies, and the water-soluble fraction of petroleum (WSFP) may be responsible for much of the toxic effects. In the present study, genotoxicity assays and histopathological analysis of the gills were analyzed for two experimental protocols: 1) Juvenile Centropomus parallelus were exposed to different concentrations of WFSP (0%, 25%, 50% and 75%) for 96h; 2) A second fish group was exposed to 50% WFSP for 168h followed by a post-exposure period for 168h in clean water (recovery). The total benzene, toluene, ethyl benzene and xylene (BTEX) and polycyclic aromatic hydrocarbon (PAH) concentrations at time 0 were 254µgL-1 and 4.72µgL-1 in 25%; 552.9µgL-1 and 9.36µgL-1 in 50%; and 842.4µgL-1 and 9.97µgL-1 in 75% WSFP, respectively. Based on the alkaline comet assay, the damage index (DI) values of fish exposed to 25% WSFP for 96h were significantly higher than those in the control group, and in the micronucleus test, the higher damage values were found in fish exposed to 75% WSFP. Furthermore, this last genotoxic test showed recovery after 168h. At all concentrations of WSFP, several histopathological changes were observed, and overall, most of these changes observed in the gills were classified as proliferative changes and represented a protective mechanism against pollutant uptake. Based on the recovery experiment, the damage was also significantly reduced after recovery. Our results showed that short-term exposure to WSFP compounds triggered cellular alterations in C. parallelus, but total recovery did not occur with time. Additionally, the different periods of exposure were not sufficient to induce severe gill damage in C. parallelus. Moreover, this fish demonstrated its usefulness as a sentinel species.