Socio-economic factors affecting the distribution of marine litter: The Portuguese case study.

Marine litter is a growing global problem with serious environmental, economic, social, and health threats. Understanding the socio-economic factors that influence the types and amounts of litter is of utmost importance. In this study, an integrative analysis of the socio-economic factors that characterize the beach litter distribution in continental Portugal and the Azores archipelago was conducted via a cluster analysis, implementing a novel technique to support the difficult task of marine litter characterization. The results highlighted that the most abundant beach litter material is plastic (92.9 %), followed by paper (2.2 %), wood (1.5 %), and metal (1.3 %). The majority of the items could not be attributed to a specific source (46.5 %). The remaining were attributed to public litter (34.5 % of total aggregated items), fishing (9.8 %), sewage-related debris (6.4 %) and shipping (2.2 %). The top-three beach litter categories were small plastic pieces (0-2.5 cm, 43.5 %), cigarette butts (30.1 %), and medium plastic pieces (2.5-50 cm, 26.4 %). A positive relation between both municipality environment expenditures and population density and the quantity and typology of litter was found. Beach litter quantity and categories were also associated with specific economic sectors, as well as with geographical/hydrodynamic conditions, demonstrating the utility of the technique and its applicability to other regions.

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

Stemless reverse total shoulder arthroplasty: a systematic review of contemporary literature.

PURPOSE: Reverse shoulder prostheses are increasingly used for treatment of rotator cuff tear arthropathy and other degenerative shoulder diseases. In recent years, aiming for bone stock preservation has led to the design of metaphyseal humeral components without a stem. The aims of this study were to evaluate the complication and reintervention rates, as well as the clinical and radiographic outcomes in patients who underwent reverse shoulder arthroplasty (RSA) with stemless implants. METHODS: A systematic review of the literature was completed until May 2020 using PubMed, EMBASE, CINAHL and Cochrane databases, according to PRISMA guidelines. RESULTS: The literature search revealed 2942 studies, of which 13 were included in this review, with a total of 517 patients and a mean follow-up between 6.4 and 101.6 months. The total complication rate was 6.5%, while 3.3% were humeral associated complications. Finally, the rate of shoulders that underwent a reintervention was 6.7%, with 1.4% relating to a humeral component reason. Stemless RSA led to substantial improvements in patient reported outcome measures and range of motion across all studies. Scapular notching was reported in 15.2%, and lucencies around humeral component were reported in 0.8% of shoulders. CONCLUSION: Stemless RSA resulted in low complication and reintervention rates at the mid-term follow-up. The reported clinical and radiological outcomes showed that these prostheses have at least equivalent outcomes with their stemmed counterparts. Further studies are required to investigate the long-term longevity and performance of the stemless humeral implants. LEVEL OF EVIDENCE: Level IV; Systematic Review.

Can biochemical endpoints improve the sensitivity of the biomonitoring strategy using bioassays with standard species, for water quality evaluation?

The Water Framework Directive (WFD) was adopted in 2000 and is a common framework for water policy, management and protection in Europe. The WFD assesses specific parameters; however, it ignores indicators of ecosystem functioning and sub-individual performance. Reservoirs are strongly influenced by anthropogenic activities that promote their imbalance. Bioassays and biomarkers are useful tools to link the chemical, ecological and toxicological assessments in water quality assessments. These approaches can be complementary to WFD methodologies, allowing the detection of impacts on the ecosystem. This study evaluated if the biochemical parameters can improve the sensitivity of the biomonitoring strategy using bioassays with the standard species Daphnia magna, in the assessment of the ecological quality of water reservoirs. To this end, water samples of Portuguese reservoirs were analysed in three sampling periods (Autumn 2018 and Spring, Autumn 2019). In parallel, a physicochemical characterization of waters was performed. D. magna feeding rate assays were performed for 24 h. After exposure, metabolism, oxidative stress and lipid peroxidation biomarkers were evaluated. Feeding rate assays showed sensitivity to different reservoirs. Biomarkers showed a higher sensitivity and can therefore improve the sensitivity of the biomonitoring strategy using bioassays. Bioassays and biomarkers approach allowed to highlight potential sources of stress, more related to the quality of the seston than to chemical contamination. This work highlights the complementarity between bioassays and biomarkers to identify ecotoxicological effects of surface waters, and can be extremely useful, especially in cases where the biotic indices are difficult to establish, such as reservoirs.

Assessment of water quality in Aguieira reservoir: Ecotoxicological tools in addition to the Water Framework Directive.

To assess the ecological potential (EP), the Water Framework Directive (WFD) uses specific parameters but ignores ecosystem functioning and individual/subindividual biological responses. The heavily modified water bodies (reservoirs) are strongly influenced by human activities that promote their imbalance, with a loss or compromise the biodiversity and the functioning of these ecosystems. This work aims to determinate the EP according physical, chemical and biological parameters of WFD and evaluate the functionality and sensitivity of ecotoxicological tools in the evaluation of water quality of Aguieira reservoir. Four sampling sites were defined in Aguieira reservoir and sampling was conducted in autumn 2018, spring and autumn 2019. WFD showed overall that Aguieira reservoir presented moderate EP. The autumn samples and the two reservoir upstream sites had the worst classification. These results were complemented by a set of ecotoxicological assays (growth inhibition of Raphidocelis subcapitata and Spirodela polyrhiza, and feeding rate of Daphnia longispina) using three natural water treatments. R. subcapitata was the most sensitive species, indicating the presence of a risk that is not detected by chemical analysis, nor by organisms of different trophic levels. D. longispina only showed sensitivity in A3 and A4 in autumn, however this results was difficult to interpret since no reason can be observed to respond the F1 lower feeding rate observed in almost sites. S. polyrhiza, as well as the total chlorophyll, lipid peroxidation, and proline content did not show sensitivity, since no discrimination among the water treatments were recorded. The relevance of bioassays is associated with the fact that an integrated response to a complex mixture can be obtained, which can contain more substances than the measured ones. Thus, we may conclude that WFD are insufficient to draw conclusions about water quality, and the growth inhibition of Raphidocelis subcapitata assay is an important parameter to complement the WFD. In addition, species of different trophic levels are recommended for ecotoxicological analyses due to differences in species sensitivities.

Complete pathological response (pCR) in gastroesophageal cancer: Correlation with metabolic response.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with resectable esophageal or esophagogastric junctional (GEJ) (Siewert I) cancer is associated with long term overall survival benefits. Up to one third of all patients submitted to nCRT present pathological complete response (pCR). 18F-fluorodeoxyglucose positron emission tomography with CT (18F-FDG PET-CT) is an important tool for assessing treatment response. Purpose was to assess retrospectively the power of 18F-FDG PET-CT in predicting pCR to evaluate the feasibility of a "watch and wait" approach. PATIENTS AND METHODS: Retrospective analysis of a prospective database with esophageal or GEJ submitted to pre-operative chemoradiation. Pre and pos treatment 18F-FDG PET-CT were reviewed and classified using visual assessment and PERCIST criteria and the values of maximum standard uptake value were also recorded. Patients were classified as pCR or non-PCR. 18F-FDG PET-CT and pathological findings were compared against each other. RESULTS: Forty-three patients were included. The median age was 67 years and 90.7% were male. All patients underwent preoperative CRT and were evaluated with 18F-FDG PET-CT pre and post treatment. Transthoracic surgery was performed in all patients. Histological type was adenocarcinoma in 37% and squamous cell carcinoma in 58%. pCR was achieved in 56% of cases. Visual assessment of 18F-FDG PET-CT showed overall sensitivity 57.9%, specificity 62.5% and PERCIST criteria had 100% sensibility and 16.7% specificity. CONCLUSIONS: 18F-FDG PET-CT is not an ideal predictor of pCR but if we use the PERCIST criteria we will have a high sensitivity and negative predictive value, avoiding false negative scans.

Ecophysiological traits of highly mobile large marine predators inferred from nucleic acid derived indices.

Nucleic acid-derived indices such as RNA/DNA ratios have been successfully applied as ecophysiological indicators to assess growth, nutritional condition and health status in marine organisms given that they provide a measure of tissue protein reserves, which is known to vary depending on changes in the environment. Yet, the use of these biochemical indices on highly mobile large predators is scarce. In this study, we tested the applicability of using nucleic acids to provide insights on the ecophysiological traits of two marine mammal species (common bottlenose dolphins and short-finned pilot whales) and explored potential related factors (species, sex, season, and residency pattern), using skin tissue (obtained from biopsy darts) of apparently healthy and adult free-ranging animals. Significantly higher RNA/DNA ratios were obtained for bottlenose dolphins (p < 0.001), and for visitor pilot whales when compared with resident pilot whales (p = 0.001). No significant changes were found between the sexes. Based on the percentile approach, the samples contain individuals in a general good condition (as the 10th percentile is not closer to the mean than the 75th percentile), suggesting that the studied region of Macaronesia may be considered an adequate habitat. The combination of this effective tool with genetic sexing and photographic-identification provided an overall picture of ecosystem health, and although with some limitations and still being a first approach, it has the applicability to be used in other top predators and ecosystems.

Manejo perioperatorio de feocromocitoma y paraganglioma / Perioperative management of paragangliomas and pheochromocytomas

Los feocromocitomas y paragangliomas son tumores neuroendocrinos raros, caracterizados por una alta tasa de morbilidad debida a un exceso de niveles de catecolaminas. Este exceso de catecolaminas es independiente de los estresores fisiológicos. Para el diagnóstico de un feocromocitoma-paraganglioma son fundamentales las pruebas bioquímicas. Las más utilizadas son las metanefrinas fraccionadas urinarias o metanefrinas libres plasmáticas. Seguido del diagnóstico bioquímico, debe realizarse un estudio imagenológico. La evaluación del paciente con diagnóstico de feocromocitoma-paraganglioma debe realizarse teniendo presente sus principales causas de morbimortalidad perioperatoria. Las dos grandes intervenciones que han disminuido la mortalidad perioperatoria son la introducción del α bloqueo y la restauración de la volemia. El otro gran avance ha sido la introducción de la cirugía laparoscópica como el estándar de oro para el abordaje quirúrgico. En relación con el manejo intraoperatorio, no se ha identificado que alguna técnica anestésica sea superior a otra. Sí se ha logrado establecer criterios de inestabilidad hemodinámica que se correlacionan con mayor morbilidad, por lo que los principales objetivos intraoperatorios son mantener estabilidad hemodinámica. El avance en el manejo preoperatorio e intraoperatorio con la consecuente disminución en la mortalidad relacionada a esta patología ha llevado el foco al manejo postoperatorio tanto agudo como a largo plazo. También se debe considerar el riesgo de recurrencia tumoral, por lo que estos pacientes deben tener un control anual de por vida.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, characterized by a high morbidity rate due to catecholamine excess. These high levels are independent of physiologic stressors. For the diagnosis, a biochemical workup is paramount. The most widely used are plasma-free metanephrines and urinary fractionated metanephrines. Imaging studies should be initiated once the biochemical diagnosis is established. Evaluation of the patient with pheochromocytomas and paragangliomas must be done taking into account the leading causes of perioperative morbidity and mortality. The two primary interventions that have reduced perioperative mortality are alpha-adrenergic blockade and intravascular volume normalization. Another significant advance has been the establishment of laparoscopic surgery as the gold standard for the surgical approach. No anesthetic technique has been found to be superior to another. Intraoperative hemodynamic instability has been correlated with poorer outcomes; thus one of the main intraoperative goals is maintaining hemodynamic stability. Lower morbidity and almost zero mortality rates due to preoperative and intraoperative management improvements have led to a focus on the immediate and long-term postoperative care. Anual lifelong follow-up is recommended to detect recurrent disease.

Mortality risk among women exposed to violence in Brazil: a population-based exploratory analysis.

OBJECTIVES: The objective of this study was to estimate mortality risk among women exposed to violence in Brazil using population-based data. STUDY DESIGN: This study used a linked database containing nearly 800,000 violence (against women) notifications and 16,500 associated deaths over the period 2011-2016. METHODS: Aggregate age-standardized population-based rates of mortality were built to estimate risk ratios (RRs) at the national and state level, and for different forms of violence and causes of death, as well as type of offender involved, and across various characteristics of the women. RRs compared the rate of mortality among women exposed to violence with that in the general population of women - excess mortality due to violence was also derived from this comparison. The analysis was divided into two time periods (2011-13 and 2014-16). RESULTS: During 2014-16, women exposed to violence had an estimated mortality risk that was 8.3 [95% confidence interval (CI): 8.2-8.5] times higher than that of the general woman population, and an estimated 100 women died on a weekly basis as a direct or indirect consequence of exposure to violence. Higher (all-cause) mortality risk was associated with physical violence and violence that involved repetition and that was self-inflicted. The risk of mortality increased when the cause of death involved external causes (RR: 51.2, 95% CI: 49.6-52.8). When death was attributable to (i) non-communicable diseases and (ii) communicable, maternal, neonatal, and nutritional diseases, the risk was 5.4 [95% CI: 5.3-5.6] and 6.7 [95% CI: 6.1-7.2] times, respectively. Women at greatest (all-cause) mortality risk include white and multiracial (parda) and single women in the age group 10-29 years, who live in the northeast part of the country. When the offender was a partner/ex., women aged 10-19 years showed the greatest (all-cause) mortality risk at 16.9 [95% CI: 13.9-19.8] times. Higher risk was also observed within the age group 30-59 years when death was attributable to external causes (RR: 74.6, 95% CI: 71.3-77.9). For younger women and girls, there was a clear gradient in (all-cause) mortality risk, with those living in the poorest municipalities at greater risk. Age-specific mortality risk also showed significant variation within and across states. CONCLUSIONS: This analysis suggests that most women exposed to violence will likely experience an increased risk of mortality, regardless of her place of residence, age group, racial/ethnic background, marital status situation, and socio-economic status. The estimated RRs are only an approximation given the design of this analysis and should be interpreted with caution.

Direct monitoring of breast and endometrial cancer cell epigenetic response to DNA methyltransferase and histone deacetylase inhibitors.

DNA methylation and histone deacetylation are key epigenetic processes involved in normal cellular function and tumorigenesis. Therapeutic strategies based on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors are currently in use and under development for the treatment of cancers. Genome-wide DNA methylation profiling has been proposed for use in disease diagnosis, and histone modification profiling for disease stratification will follow suit. However, whether epigenome sequencing technologies will be feasible for rapid clinic diagnosis and patient treatment monitoring remains to be seen, and alternative detection technologies will almost certainly be needed. Here we used electrochemical impedance spectroscopy (EIS) employing a graphene-based screen-printed electrode system to directly measure global DNA methylation and histone H3 acetylation to compare non-cancer and breast cancer cell lines. We demonstrated that whilst global methylation was not useful as a differential marker in the cellular systems tested, histone H3 acetylation was effective at higher chromatin levels. Using breast and endometrial cancer cell models, EIS was then used to monitor cellular responses to the DNMT and HDAC inhibitors 5-Aza-2'-deoxycytidine and suberoylanilide hydroxamic acid in vitro, and proved very effective at detecting global cellular responses to either treatment, indicating that this approach could be useful in following treatment response to epigenetic drugs. Moreover, this work reports the first combined analysis of two epigenetic markers using a unified graphene-based biosensor platform, demonstrating the potential for multiplex analysis of both methylation and acetylation on the same sample.

Intracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype.

HFE-hemochromatosis is a disease characterized by a systemic iron overload phenotype mainly associated with mutations in the HFE protein (HFE) gene. Osteoarthritis (OA) has been reported as one of the most prevalent complications in HFE-hemochromatosis patients, but the mechanisms associated with its onset and progression remain incompletely understood. In this study, we have characterized the response to high iron concentrations of a primary culture of articular chondrocytes isolated from newborn Hfe-KO mice and compared the results with that of a similar experiment developed in cells from C57BL/6 wild-type (wt) mice. Our data provide evidence that both wt- and Hfe-KO-derived chondrocytes, when exposed to 50 µM iron, develop characteristics of an OA-related phenotype, such as an increased expression of metalloproteases, a decreased extracellular matrix production, and a lower expression level of aggrecan. In addition, Hfe-KO cells also showed an increased expression of iron metabolism markers and MMP3, indicating an increased susceptibility to intracellular iron accumulation and higher levels of chondrocyte catabolism. Accordingly, upon treatment with 50 µM iron, these chondrocytes were found to preferentially differentiate toward hypertrophy with increased expression of collagen I and transferrin and downregulation of SRY (sex-determining region Y)-box containing gene 9 (Sox9). In conclusion, high iron exposure can compromise chondrocyte metabolism, which, when simultaneously affected by an Hfe loss of function, appears to be more susceptible to the establishment of an OA-related phenotype.

Taxonomy of Physaloptera mirandai (Nematoda: Physalopteroidea) based in three-dimensional microscopy and phylogenetic positioning.

Gastrointestinal nematodes are important ecological assets for the maintenance of the biodiversity in the Atlantic Forest in Brazil. They parasitize a number of animals of the local fauna, in which some species can promote serious injuries in the stomach wall of their hosts, which may lead to death. Among these nematodes, parasites of the genus Physaloptera are known to parasitize mammals (particularly carnivores and small rodents), birds and reptiles, being important for the local biodiversity. In this work, three hundred and sixty-two nematodes were recovered from the stomach of twenty-one Metachirus nudicaudatus (Didelphimorphia: Didelphidae) collected in Duas Bocas Biological Reserve, State of Espírito Santo, one of the largest Atlantic Forest remnants and important wildlife refuge of the Atlantic Forest in Brazil. Analysis using fluorescence and scanning electron microscopy as well as phylogenetic assessment using the mitochondrial cytochrome c oxidase subunit I gene showed that the parasites belong to the Physaloptera. Our results show details of the nematode morphology including the cloacal papillae distribution, cuticular topography details, 2D and 3D measurements of the structures with taxonomic importance. Molecular data confirmed the validity of P. mirandai and the phylogeny supported the monophyly of the assemblage formed by Physaloptera and Turgida. The use of a combination of quantitative and multidimensional microscopy tools, such as 3D reconstruction and modeling, allied to phylogenetic analysis may provide grounds for a new approach on helminth taxonomy and structural characterization.

Correction: Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis.

[This corrects the article DOI: 10.1371/journal.pone.0207441.].

Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis.

Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.

Gloeothece sp. as a Nutraceutical Source-An Improved Method of Extraction of Carotenoids and Fatty Acids.

The nutraceutical potential of microalgae boomed with the exploitation of new species and sustainable extraction systems of bioactive compounds. Thus, a laboratory-made continuous pressurized solvent extraction system (CPSE) was built to optimize the extraction of antioxidant compounds, such as carotenoids and PUFA, from a scarcely studied prokaryotic microalga, Gloeothece sp. Following "green chemical principles" and using a GRAS solvent (ethanol), biomass amount, solvent flow-rate/pressure, temperature and solvent volume-including solvent recirculation-were sequentially optimized, with the carotenoids and PUFA content and antioxidant capacity being the objective functions. Gloeothece sp. bioactive compounds were best extracted at 60 °C and 180 bar. Recirculation of solvent in several cycles (C) led to an 11-fold extraction increase of ß-carotene (3C) and 7.4-fold extraction of C18:2 n6 t (5C) when compared to operation in open systems. To fully validate results CPSE, this system was compared to a conventional extraction method, ultrasound assisted extraction (UAE). CPSE proved superior in extraction yield, increasing total carotenoids extraction up 3-fold and total PUFA extraction by ca. 1.5-fold, with particular extraction increase of 18:3 n3 by 9.6-fold. Thus, CPSE proved to be an efficient and greener extraction method to obtain bioactive extract from Gloeothece sp. for nutraceutical purposes-with low levels of resources spent, while lowering costs of production and environmental impacts.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Is there association between human development index and tuberculosis mortality risk? Evidence from a spatial analysis study in the south of Brazil.

The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008-2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0-27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49-1.66, 0.90 (0.19) and 0-6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.

Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.

BACKGROUND: Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2). RESULTS: Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-ß and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. CONCLUSION: LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.

SHORT-COMMUNICATION Evaluation of perfused bovine udder for gene expression studies in dairy cows.

Intramammary infections are one of the main causes of productivity loss in dairy cows. To better understand the immune system response and to avoid the use of live animals, we validated the use of isolated bovine udder as an ex situ model. Six mammary glands were collected from cows ready for culling. Three udders were perfused with Tyrode's solution and three were not-perfused. During six hours, we collected perfusate samples for biochemical analysis. We also collected alveolar and teat canal tissue to evaluate gene expression. The biochemical parameters indicated that the perfused udders remained viable for the entire period of the experiment. A real-time polymerase chain reaction showed an increase in 18S rRNA gene expression in the alveolar tissue at 3 and 4 h after perfusion. There was also an increase in the Ubiquitin gene in the teat canal from not-perfused udders at 1, 3, and 4 h after slaughter. In general, gene expression was stable during the experiment. Our results indicated that the isolated perfused bovine udder model is appropriate for genetic studies, opening a new perspective in animal experimentation methods.