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Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.
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Infecciones Bacterianas/inmunología , Desarrollo Embrionario/inmunología , Glucocorticoides/efectos adversos , Efectos Tardíos de la Exposición Prenatal/genética , Animales , Infecciones Bacterianas/genética , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/patología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Dexametasona/farmacología , Desarrollo Embrionario/genética , Femenino , Glucocorticoides/inmunología , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Interleucina-4/farmacología , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Neoplasias/inducido químicamente , Neoplasias/genética , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/patología , Receptores de Glucocorticoides/genética , Transducción de Señal/genéticaRESUMEN
Although sensitizing processes occur earlier, schizophrenia is diagnosed in young adulthood, which suggests that it might involve a pathological transition during late brain development in predisposed individuals. Parvalbumin (PV) interneuron alterations have been noticed, but their role in the disease is unclear. Here we demonstrate that adult LgDel+/- mice, a genetic model of schizophrenia, exhibit PV neuron hypo-recruitment and associated chronic PV neuron plasticity together with network and cognitive deficits. All these deficits can be permanently rescued by chemogenetic activation of PV neurons or D2R antagonist treatments, specifically in the ventral hippocampus (vH) or medial-prefrontal cortex during a late-adolescence-sensitive time window. PV neuron alterations were initially restricted to the hippocampal CA1/subiculum, where they became responsive to treatment in late adolescence. Therefore, progression to disease in schizophrenia-model mice can be prevented by treatments supporting vH-mPFC PV network function during a sensitive time window late in adolescence, suggesting therapeutic strategies to prevent the outbreak of schizophrenia.
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Disfunción Cognitiva/terapia , Antagonistas de los Receptores de Dopamina D2/farmacología , Hipocampo/efectos de los fármacos , Interneuronas/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Esquizofrenia/terapia , Adolescente , Animales , Modelos Animales de Enfermedad , Hipocampo/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Parvalbúminas/metabolismo , Corteza Prefrontal/patologíaRESUMEN
Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.
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Factor 15 de Diferenciación de Crecimiento/metabolismo , Hígado/metabolismo , Sepsis/patología , Animales , Anticuerpos/farmacología , Modelos Animales de Enfermedad , Factor 15 de Diferenciación de Crecimiento/sangre , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/inmunología , Corazón/efectos de los fármacos , Corazón/virología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Norepinefrina/metabolismo , Orthomyxoviridae/patogenicidad , Poli I-C/toxicidad , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Sepsis/sangre , Sepsis/mortalidad , Tasa de Supervivencia , Triglicéridos/sangre , Triglicéridos/metabolismo , Troponina I/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.
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Alérgenos , Reacción de Prevención , Hipersensibilidad a los Alimentos , Animales , Ratones , Alérgenos/inmunología , Reacción de Prevención/fisiología , Núcleo Amigdalino Central/fisiología , Modelos Animales de Enfermedad , Hipersensibilidad a los Alimentos/genética , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Intestinos/inmunología , Mastocitos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Núcleos Parabraquiales/fisiología , Núcleo Solitario/fisiologíaRESUMEN
The expansion of oil palm plantations has led to land-use change and deforestation in the tropics, which has affected biodiversity. Although the impacts of the crop on terrestrial biodiversity have been extensively reviewed, its effects on freshwater biodiversity remain relatively unexplored. We reviewed the research assessing the impacts of forest-to-oil palm conversion on freshwater biota and the mitigating effect of riparian buffers on these impacts. We searched for studies comparing taxa richness, species abundance, and community composition of macroinvertebrates, amphibians, and fish in streams in forests (primary and disturbed) and oil palm plantations with and without riparian buffers. Then, we conducted a meta-analysis to quantify the overall effect of the land-use change on the 3 taxonomic groups. Twenty-nine studies fulfilled the inclusion criteria. On average, plantations lacking buffers hosted 44% and 19% fewer stream taxa than primary and disturbed forests, respectively. Stream taxa on plantations with buffers were 24% lower than in primary forest and did not differ significantly from disturbed forest. In contrast, stream community composition differed between forests and plantations regardless of the presence of riparian buffers. These differences were attributed to agrochemical use and altered environmental conditions in the plantations, including temperature changes, worsened water conditions, microhabitat loss, and food and shelter depletion. On aggregate, abundance did not differ significantly among land uses because increases in generalist species offset the population decline of vulnerable forest specialists in the plantation. Our results reveal significant impacts of forest-to-oil palm conversion on freshwater biota, particularly taxa richness and composition (but not aggregate abundance). Although preserving riparian buffers in the plantations can mitigate the loss of various aquatic species, it cannot conserve primary forest communities. Therefore, safeguarding primary forests from the oil palm expansion is crucial, and further research is needed to address riparian buffers as a promising mitigation strategy in agricultural areas.
Metaanálisis contrastando la biodiversidad de agua dulce en los bosques y las plantaciones de palma de aceite con o sin bosques ribereños Resumen La expansión de las plantaciones de palma de aceite ha derivado en cambios en el uso de suelo y deforestación en los trópicos, afectando a la biodiversidad. Existe una revisión extensa del impacto de este cultivo sobre la biodiversidad terrestre, pero sus efectos sobre la biodiversidad de agua dulce todavía no están muy documentados. Revisamos las investigaciones que han evaluado el impacto de la conversión de bosque a plantación de palma de aceite sobre la biota de agua dulce y el efecto mitigante que tienen los bosques ribereños sobre este impacto. Buscamos estudios que compararan la riqueza de taxones, abundancia de especies y composición comunitaria de los macroinvertebrados, anfibios y peces en los riachuelos de los bosques (primarios y perturbados) y los sembradíos de palma de aceite con y sin bosques ribereños. Después realizamos un metaanálisis para cuantificar el efecto del cambio de uso de suelo en los tres grupos taxonómicos. Veintinueve estudios cumplieron con el criterio de inclusión. En promedio, las plantaciones carentes de bosques ribereños albergaron 44% y 19% menos taxones que los bosques primarios y perturbados. Los taxones en los sembradíos con bosques ribereños fueron 24% menos que en el bosque primario y no difirieron significativamente del bosque perturbado. Como contraste, la composición comunitaria del riachuelo difirió entre los bosques y los sembradíos sin importar la presencia de los bosques ribereños. Atribuimos estas diferencias al uso de agroquímicos y las condiciones ambientales alteradas en las plantaciones, incluidas los cambios térmicos, condiciones hidrológicas alteradas, pérdida de microhábitats y reducción de alimentos y refugios. En general, la abundancia no difirió significativamente entre los usos de suelo porque el incremento de especies generalistas en las plantaciones contrarresta la declinación poblacional de los especialistas de bosque vulnerables. Nuestros resultados revelan un impacto significativo de la conversión de bosque a plantación sobre la biota de agua dulce, particularmente la riqueza de taxones y la composición (pero no la abundancia agregada). Aunque mantener los bosques ribereños en las plantaciones puede mitigar la pérdida de varias especies acuáticas, no puede conservar las comunidades del bosque primario. Por lo tanto, es crucial salvaguardar los bosques primarios de la expansión del aceite de palma, además de que se necesitan más investigaciones para abordar los bosques ribereños como una estrategia prometedora de mitigación en las áreas agrícolas.
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Biodiversidad , Conservación de los Recursos Naturales , Animales , Conservación de los Recursos Naturales/métodos , Bosques , Agricultura , Agua DulceRESUMEN
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
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The present study investigated the levels of As, Ag, Al, Ba, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se, and Zn in muscle samples of six fish species (Pygocentrus nattereri, Serrasalmus marginatus, Mylossoma duriventre, Leporinus friderici, Pimelodus argenteus, and P. pantaneiro) highly consumed by local riverine and non-resident people in middle Miranda River, southern Brazilian Pantanal. Significant differences were detected for Ba, Fe, Mn, and Zn levels among the analyzed species. Pairwise comparison detected significant differences in element levels between species with similar diets, which implies that other factors, instead of species' feeding habits, could be involved in distinct levels of element bioaccumulation. Significant correlations between body size and concentrations were found for Ba in P. nattereri (moderate positive correlation), and for Mn in M. duriventre (weak positive correlation) and P. argenteus (moderate negative correlation). Levels exceeding tolerable daily intake (TDI) were found for Pb maximum concentrations in P. nattereri, M. duriventre, L. friderici, P. argenteus, and P. pantaneiro, and for Cd maximum concentration in P. argenteus. Health risk assessment indicated considerable risk only for the worst-case scenario (calculated from maximum concentrations) for all species. Adopting a Pb monitoring program in biotic and abiotic compartments in Miranda River is strongly recommended.
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Peces , Ríos , Contaminantes Químicos del Agua , Animales , Brasil , Ríos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Contaminación de Alimentos/análisisRESUMEN
Background: This article identifies the factors associated with burnout among dentists in the state of Bahia, Brazil, during the COVID-19 pandemic. Methods: A cross-sectional study, conducted between November 2020 and February 2021, of 251 dentists, selected by snowball sampling. Sociodemographic, occupational, and epidemiological information was collected in an electronic form. Burnout was evaluated through the Maslach Burnout Inventory; anxiety through the Beck Anxiety Inventory; and quality of life through the WHOQol-BREF questionnaire. Multiple linear regression was used to identify factors associated with variations in levels of the three burnout dimensions. Results: The mean levels of the burnout dimensions were: Emotional Exhaustion: 28.9 ± 8.9 (SD); Depersonalization = 8.2 ± 6.3; and Personal Accomplishment: 28.0 ± 6.2. The proportion of professionals with high Emotional Exhaustion (≥ 30 cut-off score), high Depersonalization (≥ 12 cut-off score), and low Personal Accomplishment (≤ 33 cut-off score) were 43.4%, 26.3% and 81.3%, respectively. Burnout components were associated with high anxiety; lower levels of the physical, psychological, social relations, and environmental dimensions of quality of life; less time working as a dentist; increased alcohol consumption during the pandemic, feeling safe when using personal protective equipment, and support from work fellows. Conclusion: The dentists investigated showed moderate levels of Emotional Exhaustion and Depersonalization, and very low levels of Personal Accomplishment. The prevention and mitigation of burnout syndrome among dentists during a pandemic should consider several factors, such as quality of life, amount of time in the profession, use of personal protective equipment, support from fellow dentists, and alcohol consumption.
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The beneficial pharmacological actions including antioxidant effects as an antileishmanial, antibacterial, antifungal, antidiabetic, anti-inflammatory, antitumor, antiviral, and analgesic of compounds isolated from Combretum mellifluum Eichler (Combretaceae) are well established. The aim of the present study was to determine the phytochemistry as well as assess the antioxidant and antileishmanial activities of the leaves from Combretum mellifluum Eichler (Combretaceae). Analysis of ethanolic extract resulted in isolation and identification of two epimeric mixtures of four previously unknown cycloartane-type triterpenoids, methyl quadrangularate M and methyl 24-epiquadrangularate M, and 2α,3ß,24ß-trihydroxy-cycloart-25-ene and 2α, 3ß, 24α-trihydroxy-cycloart-25-ene, and eight known compounds. Their structures were using one-dimensional nuclear magnetic resonance (1D NMR), 2D NMR and high-resolution electrospray ionization mass spectroscopy (HRESIMS) analysis. Further, the extract and fractions were tested for antioxidant potential. The ethyl acetate and aqueous fractions demonstrated the highest antioxidant activity against 2,2-dipheny-1-picrylhydrazl (DPPH) free radicals, which correlated directly with total flavonoid content. All extracts and fractions from C. mellifluum Eichler were assessed for antileishmanial activity. The supernatant fraction exhibited highest potential, inhibiting the growth of Leishmania amazonensis with IC50 value 31.29 µg/ml. Our findings provide information on the chemical composition of C. mellifluum and the potential beneficial therapeutic usefulness as an antioxidant agent in various diseases.
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Combretum , Triterpenos , Antioxidantes/análisis , Antioxidantes/farmacología , Combretum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Triterpenos/análisis , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
We performed a biological evaluation of antileishmanial activity, in silico ADME-Tox profile, and molecular docking of riparins A-F. The antileishmanial activity was evaluated in Leishmania major promastigotes, whereas the cytotoxic activity was tested on murine macrophages. Computational parameters were predicted by in silico analysis. Molecular docking was performed with 18 L. major molecular targets. Riparins, especially RipC and RipE, showed cytotoxic activity in vitro toward L. major promastigotes and a high selectivity index. Riparins showed small differences in their physicochemical properties, such as polarity and aqueous solubility. LogP was an important parameter for the differences in the antileishmanial activity between the molecules. In molecular docking, the ligands displayed Ki < 1 µM for LmNMT and LmLEI. Significant molecular interactions were observed with residues from the active site and adjacent regions of such enzymes. Thus, riparins have the potential for application in antileishmanial therapy.
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Antiprotozoarios , Leishmania major , Animales , Antiprotozoarios/química , Antiprotozoarios/toxicidad , Ligandos , Macrófagos , Ratones , Simulación del Acoplamiento MolecularRESUMEN
Surface deposits of rare earth element (REE) were identified in the Bat Xat district, Northern Vietnam. As the area is inhabited, an in-depth investigation was carried out to assess the radioactivity levels and to evaluate the radiation exposure and radiological risks for the population. Samples of REE ore, soils, water and several foods locally produced were collected and analyzed by gamma spectrometry for determination of 232Th, 226Ra, and 40 K. Radon (222Rn and 220Rn) measurements were carried out in dwellings at the villages located near by the REE deposit area, and in Hanoi for comparison. Based on the measured radionuclide concentrations, several radiological parameters were calculated to evaluate the radiological risks for the population and to compare with worldwide values. Results indicate that the representative person of the most exposed group living near the REE deposits may receive a total annual effective dose as high as 37.9 ± 10.6 mSv, i.e., approximately 16 times the world average dose of 2.4 mSv y-1. Consequently, this area should be considered a high background radiation area. Exposure to external radiation and internal radiation from ingestion and inhalation of radionuclides were assessed separately. Radon inhalation contributed to approximately 70% of the total annual effective dose, with both radon isotopes contributing significantly, while the ingestion of local foods and water gave minor contributions to the total effective dose. Several measures were considered to improve the radiation safety and recommendations are given to relocate the most exposed members of the population.
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Contaminantes Radiactivos del Aire , Contaminación del Aire Interior , Quirópteros , Exposición a la Radiación , Monitoreo de Radiación , Radón , Contaminantes Radiactivos del Aire/análisis , Contaminación del Aire Interior/análisis , Animales , Radiación de Fondo , Humanos , Exposición a la Radiación/análisis , Monitoreo de Radiación/métodos , Radioisótopos , Radón/análisis , Vietnam , AguaRESUMEN
Globally, bats are of interest in many studies, beyond their ecological or epidemiological relevance or even the ecomorphological diversity of species. In Brazil, most of the indexed studies on chiropterans date from 1954, with a slow and heterogeneous progress in the publication increasing. The aim of this study was to analyze the literature on bats in Brazil, identifying patterns, tendencies and knowledge gaps in the Brazilian federal states. We carried out a sistematyzed search on the online databases Clarivate Analytics Web of Science (WoS), Scientific Electronic Library Online (SciELO), PubMed and Scopus. We used the descriptive terms "Chiroptera" and "Brazil". Besides these bases, we included data from the manuscripts published in Chiroptera Neotropical. We obtained a total of 1,115 articles, which were analyzed and classified in 22 thematic categories based on the articles' approach. We observed that each Brazilian region and state had particularities in their knowledge panoramas of bats, not being possible to generalize conditions for each federal region. Even though the increasing in the number of articles by categories, we encourage that every approach keep being developded, once no thematic could had been considered enough explored till the moment.
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Quirópteros , Animales , Bibliometría , BrasilRESUMEN
BACKGROUND: Brazil is a violent society and police officers play a fundamental role in this scenario. Police work is a stressful occupation. Dealing with routine violence, police officers must have high standards of physical and mental health. Patrolling the streets involves several risks and stressful situations that may hamper military policemen's quality of life. The identification of factors associated with health-related quality of life may help in planning and providing adequate care to military policemen. This study aimed to identify factors associated with health-related quality of life of military policemen in Salvador, Brazil. METHODS: A cross-sectional design study investigated a random sample of 329 male military police officers, engaged in patrolling the streets of Salvador, Brazil. A structured questionnaire applied to the policemen collected information about age, education, marital status, income, house ownership, car ownership, police rank, working day, alcohol consumption, smoking, frequency of vigorous physical activity, obesity (body mass index ≥ 30.0), and work ability. Health-related quality of life was evaluated through the 36-Item Short Form Health Survey Questionnaire (SF-36). Work ability was assessed through the Work Ability Index questionnaire. Poor work ability was defined by a 7-27 points score. Multiple linear regression models were used to measure the impact of police officers characteristics on the variation in the Physical Component and Mental Component Summary scores. RESULTS: Normalised scores were below 50.0% for seven out of the eight SF-36 domains and for the two component summaries. The SF-36 Physical Component Summary was significantly (P < 0.05) associated with poor work ability, while the Mental Component Summary was associated with poor work ability, excessive alcohol consumption, and younger age (24-34 years). Multivariate analysis estimated that the Physical Component Summary was 7.386 units (%) lower among policemen with poor work ability compared to those with moderate/good/excellent work ability. The Mental Component Summary was 12.755 units lower among those with poor work ability, 5.354 units lower among those with excessive alcohol consumption, and 5.532 units higher among those with younger age. CONCLUSIONS: The military police officers investigated presented low health-related quality of life, associated with younger age, excessive alcohol consumption, and poor work ability.
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Personal Militar/psicología , Policia/psicología , Calidad de Vida , Adulto , Brasil , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Rendimiento Laboral , Recursos Humanos , Adulto JovenRESUMEN
Tantalite and columbite ores have been reported as containing associated primordial radionuclides, such as uranium and thorium. Ethiopia is one of the world suppliers of tantalite ore through exploitation of Kenticha mine and tantalite production by a large number of artisanal miners. For the purpose of implementing the international standards for radiation protection of workers and members of the public, a preliminary assessment of radionuclides and radiation doses associated to tantalite mining was performed. Results confirmed and quantified the co-occurrence of uranium and thorium and their progeny in tantalite ore. Radiation doses at some workplaces may exceed the effective dose limit recommended by the international radiation safety standards for nonradiation workers and members of the public. Investments to be made in order to expand and modernize tantalite production in Ethiopia shall take into account the radiation hazards and implement a radiation protection program to prevent enhanced occupational radiation exposures and protect the public and the environment.
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Exposición Profesional , Exposición a la Radiación , Monitoreo de Radiación , Uranio , Etiopía , Humanos , Minería , Exposición Profesional/análisis , Óxidos , Radioisótopos/análisis , Tantalio , Uranio/análisisRESUMEN
In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.
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Anfotericina B , Antiprotozoarios , Ácido Elágico , Leishmania major , Leishmaniasis Cutánea , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Ácido Elágico/farmacología , Leishmaniasis Cutánea/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. OBJECTIVES: To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. METHODS: Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. RESULTS: The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p = 0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p = 0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p = 0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p = 0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. CONCLUSION: HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.
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Lesión Renal Aguda/sangre , Biomarcadores/sangre , Proteína HMGB1/sangre , Interleucina-6/sangre , Cirrosis Hepática/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
This study aimed to verify possible alterations involving histological and oxidative stress parameters in the lungs of wild bats in the Carboniferous Basin of Santa Catarina (CBSC) state, Southern Brazil, as a means to evaluate the impact of coal dust on the health of wildlife. Specimens of frugivorous bat species Artibeus lituratus and Sturnira lilium were collected from an area free of coal dust contamination and from coal mining areas. Chemical composition, histological parameters, synthesis of oxidants and antioxidant enzymes, and oxidative damage in the lungs of bats were analyzed. Levels of Na, Cl, Cu, and Br were higher in both species collected in the CBSC than in the controls. Levels of K and Rb were higher in A. lituratus, and levels of Si, Ca, and Fe were higher in S. lilium collected in the carboniferous basin. Both bat species inhabiting the CBSC areas exhibited an increase in the degree of pulmonary emphysema compared to their counterparts collected from control areas. Sturnira lilium showed increased reactive oxygen species (ROS) and 2',7'-dichlorofluorescein (DCF) levels, while A. lituratus showed a significant decrease in nitrite levels in the CBSC samples. Superoxide dismutase (SOD) activity did not change significantly; however, the activity of catalase (CAT) and levels of glutathione (GSH) decreased in the A. lituratus group from CBSC compared to those in the controls. There were no differences in NAD(P)H quinone dehydrogenase 1 protein (NQO1) abundance or nitrotyrosine expression among the different groups of bats. Total thiol levels showed a significant reduction in A. lituratus from CBSC, while the amount of malondialdehyde (MDA) was higher in both A. lituratus and S. lilium groups from coal mining areas. Our results suggested that bats, especially A. lituratus, living in the CBSC could be used as sentinel species for harmful effects of coal dust on the lungs.
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Quirópteros , Minas de Carbón , Carbón Mineral/toxicidad , Pulmón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Brasil , Catalasa/metabolismo , Quirópteros/anatomía & histología , Quirópteros/metabolismo , Polvo , Glutatión/metabolismo , Pulmón/anatomía & histología , Pulmón/química , Pulmón/metabolismo , Malondialdehído/metabolismo , Metales/análisis , Modelos Biológicos , Enfisema Pulmonar/veterinaria , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cutaneous leishmaniasis is a neglected parasitic disease. Treatment is preferably performed with pentavalent antimony associated or not with amphotericin B (AmB). This study aimed to develop an emulgel with different chemical enhancers of cutaneous release. Initially, AmB emulsions were obtained with the chemical promoters, oleic acid and geraniol and without promoter, then for the evaluation of the formulations, a preliminary stability study was carried out where the formulations were submitted to centrifugation, before and after the freeze-thaw cycle and analyzed appearance, color, pH, spreadability, viscosity, conductivity, droplet size, assay, in vitro release study, in vitro antileishmania activity in Leishmania major promastigotes, and macrophage toxicity in the MTT test. The emulsions were yellowish, with no signs of instability after the centrifugation test. The pH range corresponded to that of the skin, which is 4.6 to 5.8, before and after the freeze-thaw cycle, the formulations had good spreadability and did not present significant viscosity differences before and after the freeze-thaw cycle, presenting a non-Newtonian characteristic. AmB content was within the kinetic model of zero order release, the formulation of 3% AmB and 5% oleic acid (formulation 1) was chosen to proceed with the antileishmania activity test and showed potential activity against the in vitro parasite with significant reduction of cytotoxicity on murine macrophages, indicating that the formulation is promising for the treatment of cutaneous leishmaniasis.
Asunto(s)
Anfotericina B/administración & dosificación , Antiprotozoarios/administración & dosificación , Leishmaniasis Cutánea/tratamiento farmacológico , Anfotericina B/química , Anfotericina B/uso terapéutico , Animales , Antiprotozoarios/química , Antiprotozoarios/uso terapéutico , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Emulsiones , Concentración de Iones de Hidrógeno , Ratones , ViscosidadRESUMEN
Measures of traits are the basis of functional biological diversity. Numerous works consider mean species-level measures of traits while ignoring individual variance within species. However, there is a large amount of variation within species and it is increasingly apparent that it is important to consider trait variation not only between species, but also within species. Mammals are an interesting group for investigating trait-based approaches because they play diverse and important ecological functions (e.g., pollination, seed dispersal, predation, grazing) that are correlated with functional traits. Here we compile a data set comprising morphological and life history information of 279 mammal species from 39,850 individuals of 388 populations ranging from -5.83 to -29.75 decimal degrees of latitude and -34.82 to -56.73 decimal degrees of longitude in the Atlantic forest of South America. We present trait information from 16,840 individuals of 181 species of non-volant mammals (Rodentia, Didelphimorphia, Carnivora, Primates, Cingulata, Artiodactyla, Pilosa, Lagomorpha, Perissodactyla) and from 23,010 individuals of 98 species of volant mammals (Chiroptera). The traits reported include body mass, age, sex, reproductive stage, as well as the geographic coordinates of sampling for all taxa. Moreover, we gathered information on forearm length for bats and body length and tail length for rodents and marsupials. No copyright restrictions are associated with the use of this data set. Please cite this data paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data.
RESUMEN
MOTIVATION: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. MAIN TYPES OF VARIABLES INCLUDED: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. SPATIAL LOCATION AND GRAIN: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2). TIME PERIOD AND GRAIN: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. MAJOR TAXA AND LEVEL OF MEASUREMENT: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. SOFTWARE FORMAT: .csv and .SQL.