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Nicotinamide riboside (NR), a NAD+ precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD+ availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 µM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD+ increase after 192 h. NR concentrations greater than 1 µM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 µM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.
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Metabolismo Energético , Niacinamida , Compuestos de Piridinio , Humanos , Niacinamida/análogos & derivados , Niacinamida/farmacología , Compuestos de Piridinio/farmacología , Metabolismo Energético/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Línea Celular , Apoptosis/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Proliferación Celular/efectos de los fármacos , Reprogramación MetabólicaRESUMEN
Lipids play key roles in the body, influencing cellular regulation, function, and signalling. Tolcapone, a potent catechol-O-methyltransferase (COMT) inhibitor described to enhance cognitive performance in healthy subjects, was previously shown to impact fatty acid ß-oxidation and oxidative phosphorylation. However, its impact on the brain lipidome remains unexplored. Hence, this study aimed to assess how tolcapone affects the lipidome of the rat pre-frontal cortex (PFC), a region of the brain highly relevant to tolcapone therapeutic effect, while evaluating its influence on operant behaviour. Tolcapone at 20 mg/kg was chronically administered to Wistar rats during a behavioural task and an untargeted liquid chromatography high-resolution mass spectrometry (LC-HR/MS) approach was employed to profile lipid species. The untargeted analysis identified 7227 features, of which only 33% underwent statistical analysis following data pre-processing. The results revealed an improved cognitive performance and a lipidome remodelling promoted by tolcapone. The lipidomic analysis showed 32 differentially expressed lipid species in tolcapone-treated animals (FC ≥ 1.2, p-value ≤ 0.1), and among these several triacylglycerols, cardiolipins and N-acylethanolamine (NAE 16:2) were found upregulated whereas fatty acids, hexosylceramides, and several phospholipids including phosphatidylcholines and phosphatidylethanolamines were downregulated. These preliminary findings shed light on tolcapone impact on lipid pathways within the brain. Although tolcapone improved cognitive performance and literature suggests the significance of lipids in cognition, this study did not conclusively establish that lipids directly drove or contributed to this outcome. Nevertheless, it underscores the importance of lipid modulation and encourages further exploration of tolcapone-associated mechanisms in the central nervous system (CNS).
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Catecol O-Metiltransferasa , Lipidómica , Humanos , Ratas , Animales , Tolcapona/metabolismo , Tolcapona/farmacología , Benzofenonas , Nitrofenoles , Inhibidores Enzimáticos/farmacología , Ratas Wistar , Dopamina/metabolismo , Inhibidores de Catecol O-Metiltransferasa/farmacología , Encéfalo/metabolismo , LípidosRESUMEN
Lymphangioleiomyomatosis (LAM) is a rare systemic disease that typically presents like cystic lung disease. High-resolution computed tomography (CT) is the recommended imaging technique, with cysts being the hallmark: typically multiple, well-circumscribed, thin-walled, with a variable diameter (usually <2 cm) and widespread in distribution. The gold standard for diagnosis is a biopsy. LAM should be considered in the differential diagnosis of cystic lung diseases. The authors report a case of LAM presenting with a pneumothorax, which due to its atypical imaging characteristics, mimicked another uncommon cystic disease. A multidisciplinary approach is crucial when dealing with presentations of rare diseases.
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A study on aerosols in the Brazilian subequatorial Amazon region, Tangará da Serra (TS) and Alta Floresta (AF) was conducted and compared to findings in an additional site with background characteristics (Manaus, AM). TS and AF counties suffer from intense biomass burning periods in the dry season, and it accounts for high levels of particles in the atmosphere. Chemical characterization of fine and coarse particulate matter (PM) was performed to quantify water-soluble ions (WSI) and black carbon (BC). The importance of explanatory variables was assessed using three machine learning techniques. Average concentrations of PM in AF and TS were similar (PM2.0, 17±10 µg m-3 (AF) and 16±11 µg m-3 (TS) and PM10-2.0, 13±5 µg m-3 (AF) and 11±7 µg m-3 (TS)), but higher than the background site. BC and SO4 2- were the prevalent components as they represented 27%-68% of particulates chemical composition. The combination of the machine learning techniques provided a further understanding of the pathways for PM concentration variability, and the results highlighted the influence of biomass burning for key sample groups and periods. PM2.0, BC, and most WSI presented higher concentrations in the dry season, providing further support for the influence of biomass burning.
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Contaminantes Atmosféricos , Material Particulado , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Biomasa , Tecnología de Sensores Remotos , Brasil , Estaciones del Año , Monitoreo del AmbienteRESUMEN
Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.
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BACKGROUND: Worsening environmental conditions may amplify people's emotional responses to an environmental crisis (eco-anxiety). In Portugal, young people seem to be especially concerned about climate change. However, this phenomenon needs to be interpreted using accurate instruments. Thus, this study aimed to validate the Portuguese version of the Hogg Eco-Anxiety Scale (HEAS) in young adults and examine the associations among eco-anxiety, sociodemographic characteristics, and pro-environmental behaviours. METHODS: A survey was administered to 623 Portuguese university students aged between 18 and 25 years. The survey included our Portuguese translation of the HEAS (obtained through a back-translation and pretesting process), a sociodemographic assessment, and questions related to pro-environmental behaviours. Confirmatory factor analysis was conducted to assess the construct validity of the Portuguese version of the HEAS, and global fit indices were used to assess whether the original four-dimensional structure of the scale was reproduced. The reliability of the Portuguese version of the HEAS was evaluated by Cronbach's alpha and the intraclass correlation coefficient. Measurement invariance examined sex differences in scale interpretation. Linear regressions were used to detect whether sociodemographic variables predict eco-anxiety and whether eco-anxiety predicts pro-environmental behaviours. RESULTS: The factorial structure of the original scale was replicated in the Portuguese version of the HEAS, showing good internal consistency, reliability over time and strict invariance between men and women. A higher paternal education level predicted greater eco-anxiety in children. Two dimensions of eco-anxiety-namely, rumination and anxiety about personal impacts on the environment-predicted higher engagement in pro-environmental behaviours. CONCLUSIONS: The translated scale is an appropriate tool to measure eco-anxiety in the Portuguese context and should be used to collect evidence to drive environmental and health policies. An individual's education level should be considered a determinant of their emotional response to environmental conditions. Importantly, eco-anxiety can act as a protective emotional response to preserving the planet.
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Ansiedad , Traducciones , Niño , Humanos , Masculino , Femenino , Adulto Joven , Adolescente , Adulto , Portugal , Reproducibilidad de los Resultados , Ansiedad/epidemiología , Encuestas y Cuestionarios , Psicometría/métodosRESUMEN
BACKGROUND: The control of the center of mass is essential for a stable and efficient gait. Post-stroke patients present several impairments, which may compromise the control of the center of mass during gait in the sagittal and frontal planes. This study aimed to identify changes in the vertical and mediolateral behavior of the center of mass during the single stance phase of post-stroke patients using the statistical parametric mapping analysis. It also aimed to identify alterations in the center of mass trajectories regarding the motor recovery stages. METHODS: Seventeen stroke patients and 11 neurologically intact individuals were analyzed. The statistical parametric mapping approach was used to identify changes in the center of mass trajectories between stroke and healthy groups. The trajectories of the center of mass of post-stroke individuals were compared according to their motor recovery status. FINDINGS: A near-flat vertical trajectory of the center of mass was indenfitifed in the stroke group compared to their healthy counterparts, especially on the paretic side. The center of mass trajectories in both directions (vertical and mediolateral) presented substantial alteration at the end of the single stance phase in the stroke group. The trajectory of the center of mass of the stroke group was symmetrical in the mediolateral direction between the sides. The trajectories of the center of mass presented similar pattern irrespective of the motor recovery status. INTERPRETATION: The statistical parametric mapping approach showed to be suitable for determining gait changes in post-stroke individuals, irrespective of their motor recovery stage.
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Trastornos Neurológicos de la Marcha , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Caminata , Marcha , Accidente Cerebrovascular/complicaciones , Trastornos Neurológicos de la Marcha/etiología , Fenómenos BiomecánicosRESUMEN
Postural instability affects motor tasks after a stroke. We investigated the strategies used to maintain balance during quiet standing posture and dynamic tasks in a video game. Sixteen stroke volunteers (12 males, 56 ± 9 years, post-stroke time 35 ± 10 months) and sixteen matched healthy volunteers had their biomechanical data collected to obtain the variables: center of mass, base of support, margin of stability, and weight symmetry. Healthy individuals and stroke patients showed similar dynamic stability. However, they adopted different motor strategies to achieve this: healthy individuals increased their base of support as they progressed to more challenging tasks, and stroke volunteers maintained the same base. The margin of stability of stroke volunteers was correlated with the MiniBEST scale.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Juegos de Video , Masculino , Humanos , Equilibrio Postural , Accidente Cerebrovascular/complicaciones , PosturaRESUMEN
Burns affect the skin and appendages, impair their function, and become favorable regions for bacterial infections. Owing to time-consuming and costly treatments, burns have been considered a public health problem. The limitations of the treatments used for burns have motivated the search for more efficient alternatives. Curcumin has several potential properties such as anti-inflammatory, healing, and antimicrobial activities. However, this compound is unstable and has low bioavailability. Therefore, nanotechnology could offer a solution for its application. This study aimed to develop and characterize dressings (or gauzes) impregnated with curcumin nanoemulsions that were prepared using two different techniques as a promising platform for skin burn treatment. In addition, the effect of cationization on curcumin release from the gauze was evaluated. Nanoemulsions were successfully prepared using two methods, ultrasound and a high-pressure homogenizer, with sizes of 135 nm and 144.55 nm, respectively. These nanoemulsions exhibited a low polydispersity index, adequate zeta potential, high encapsulation efficiency, and stability for up to 120 d. In vitro assays demonstrated a controlled release of curcumin between 2 and 240 h. No cytotoxicity was observed at concentrations of curcumin up to 75 µg/mL, and cell proliferation was observed. The incorporation of nanoemulsions in the gauze was successfully achieved, and the evaluation of curcumin release showed a faster release from cationized gauzes, whereas the non-cationized gauze promoted a more constant release.
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Quemaduras , Curcumina , Humanos , Curcumina/farmacología , Administración Cutánea , Cicatrización de Heridas , Nanotecnología , Quemaduras/tratamiento farmacológicoRESUMEN
The world of cosmetics is an always-evolving field with constant updates on its formulation components. The current reality asks for an ever-increasing need for natural and sustainable replacements for synthetic compounds in all fields of modern consumer products. However, the research and development stages of finding these alternatives can be an expensive, time-consuming, and often wasteful process that turns this task into a laborious procedure. This study introduces the development of a computational methodology that will aid the research of silicone alternatives, disclosing their structural performance in a formulation. Additionally, an equilibration protocol was developed to measure the distribution and densities of these silicone alternatives to determine how they behave in relation to their counterparts, using molecular dynamics simulations. Two systems were tested, A and B, where the former is composed of one ester (Dipentaerythrityl Hexa C5 Acid Ester) and the latter by an ester combined with an alkane (Triheptanoin and C13-Isoalkane); all three molecules are commercially available and widely used. Both systems were subjected to a 3-step thermal regulation strategy. The systems went through an initial simulation at 25 °C and at 70 °C, then a temperature switch took place (25 °C « 70 °C), then a shock to 200 °C, and finally a Simulated Annealing protocol reaching 250 °C. In the end, all systems converged towards micelle-like structures. These results come to further ascertain the position of computational chemistry and Molecular Dynamics Simulations as an important part of R&D processes in modern sciences and investigation.
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Ascertaining compound exposure and its spatial distribution are essential steps in the drug development process. Desorption electrospray ionization mass spectrometry (DESI-MSI) is a label-free imaging technique capable of simultaneously identify and visualize the distribution of a diverse range of biomolecules. In this study, DESI-MSI was employed to investigate spatial distribution of tolcapone in rat liver and brain coronal - frontal and striatal -sections after a single oral administration of 100 mg/Kg of tolcapone, brain-penetrant compound. Tolcapone was evenly distributed in liver tissue sections whereas in the brain it showed differential distribution across brain regions analyzed, being mainly located in the olfactory bulb, basal forebrain region, striatum, and pre-frontal cortex (PFC; cingulate, prelimbic and infralimbic area). Tolcapone concentration in tissues was compared using DESI-MSI and liquid-chromatography mass spectrometry (LC-MS/MS). DESI-MSI technique showed a higher specificity on detecting tolcapone in liver sections while in the brain samples DESI-MSI did not allow a feasible quantification. Indeed, DESI-MSI is a qualitative technique that allows to observe heterogeneity on distribution but more challenging regarding accurate measurements. Overall, tolcapone was successfully localized in liver and brain tissue sections using DESI-MSI, highlighting the added value that this technique could provide in assisting tissue-specific drug distribution studies.
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Encéfalo , Espectrometría de Masas en Tándem , Ratas , Animales , Tolcapona , Cromatografía Liquida , Hígado , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Well-being is transversal to different urban-related challenges such as increasing urbanization or adaptation to the effects of climate change. One possible response to these challenges is the use of nature in cities. The aim of this study is to investigate how the objective quantity of natural space near the home, the perception of these natural elements, and their perceived availability, moderated by the effect of connectedness to nature, could explain levels of well-being. A survey was conducted among a sample of 1343 participants living in seven European cities. Data were collected online via a questionnaire. Indicators of the objective quantity of urban natural space based on remotely sensed satellite imagery were also used. Regression models highlight the association between well-being and perceived amount of nature, accessibility to a community garden, and level of connectedness to nature. A moderating and negative effect of connectedness to nature on the association between the perceived quantity of nature and well-being was also identified. Perception of nature seems to be a better indicator of well-being than the objective one. Results highlight the importance of the social dimension of collective gardens in enhancing well-being. Connectedness to nature could facilitate appropriation of natural elements and its effects on well-being.
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Encuestas y Cuestionarios , Humanos , CiudadesRESUMEN
Balantioides coli is a zoonotic enteric protozoan parasite of public veterinary health relevance and a concern in animal production and food safety. While wild cervids are recognized reservoirs for several zoonotic pathogens, little is known about the occurrence of B. coli in deer species, especially in Europe. To fill this gap, a total of 130 fecal samples from legally hunted red deer (Cervus elaphus, n = 95) and fallow deer (Dama dama, n = 35) were passively collected during two hunting seasons (October to February; 2018-2019 and 2019-2020) in Portugal. After assessment by PCR assay targeting the complete ITS1-5.8s-rRNA-ITS2 region and the 3' end of the ssu-rRNA gene of the parasite, a prevalence of 4.2% (4/95, 95% CI: 0.2-8.3) in red deer and of 5.7% (2/35, 95% CI: 0.0-13.4) in fallow deer was found. Sequence and phylogenetic analyses allowed the identification of B. coli genetic variants A (in two red deer) and B (in two red deer and two fallow deer). This is the first molecular-based description of B. coli in European deer species, whose population have increased in density and geographical range in recent years. Continued monitoring of wild ungulates as potential vectors of parasitic infection diseases of zoonotic nature is crucial to safeguard public health and food safety.
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Leptospirosis in ruminants causes reproductive failures leading to important economic losses. This study assessed the occurrence and genetically identified Leptospira spp. in the follicular fluid (FF) of naturally infected live cows. A total of 251 asymptomatic cows from different commercial dairy herds were subjected to ovum-pick up technique for follicular fluid sampling. PCR was performed for Leptospira spp. detection and phylogenetic analysis was later implemented for sequencing. From 251 samples analyzed, 67 (26.7 %) were lipL32-PCR positive, confirming the presence of leptospiral DNA on FF. Furthermore, it was possible to amplify and sequence nine strains after secY nested-PCR. All of them were identified as L. interrogans, with 100 % of identity with strains belonging to Sejroe serogroup. Our findings reveal a high occurrence of infection of Leptospira in the ovarium of asymptomatic cows, highlighting the importance of considering the silent leptospirosis syndrome when screening animals for assisted reproductive biotechniques.
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Leptospira interrogans , Leptospira , Leptospirosis , Animales , Bovinos , Femenino , Genitales , Leptospira/genética , Leptospira interrogans/genética , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Filogenia , SerogrupoRESUMEN
The epigenetic changes associated with melanoma progression to advanced and metastatic stages are still poorly understood. To shed light on the CpG methylation dynamics during melanoma development, we analyzed the methylome profiles of a four-stage cell line model of melanoma progression: non-tumorigenic melanocytes (melan-a), premalignant melanocytes (4C), non-metastatic melanoma cells (4C11-), and metastatic melanoma cells (4C11+). We identified 540 hypo- and 37 hypermethylated gene promoters that together characterized a malignancy signature, and 646 hypo- and 520 hypermethylated promoters that distinguished a metastasis signature. Differentially methylated genes from these signatures were correlated with overall survival using TCGA-SKCM methylation data. Moreover, multivariate Cox analyses with LASSO regularization identified panels of 33 and 31 CpGs, respectively, from the malignancy and metastasis signatures that predicted poor survival. We found a concordant relationship between DNA methylation and transcriptional levels for genes from the malignancy (Pyroxd2 and Ptgfrn) and metastasis (Arnt2, Igfbp4 and Ptprf) signatures, which were both also correlated with melanoma prognosis. Altogether, this study reveals novel CpGs methylation markers associated with malignancy and metastasis that collectively could improve the survival prediction of melanoma patients.
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Metilación de ADN , Melanoma , Islas de CpG , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , Melanocitos/metabolismo , Melanocitos/patología , Melanoma/metabolismo , Pronóstico , Regiones Promotoras GenéticasRESUMEN
AIMS: The absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated. METHODS: Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [14 C]-opicapone. The mass balance of [14 C]-opicapone and metabolic profile were evaluated. RESULTS: The recovery of total administered radioactivity averaged >90% after 144 hours. Faeces were the major route of elimination, representing 70% of the administered dose; 5% and 20% were excreted in urine and expired air, respectively. The Cmax of total radioactivity matched that of unchanged opicapone, whereas the total radioactivity remained quantifiable for a longer period, attributed to the contribution of opicapone metabolites, involving primarily 3-O-sulfate conjugation (58.6% of total circulating radioactivity) at the nitrocatechol ring. Other circulating metabolites, accounting for <10% of the radioactivity exposure, were formed by glucuronidation, methylation, N-oxide reduction and gluthatione conjugation. Additionally, various other metabolites resulting from combinations with the opicapone N-oxide reduced form at the 2,5-dichloro-4,6-dimethylpyridine 1-oxide moiety, including nitro reduction and N-acetylation, reductive opening and cleavage of the 1,2,4-oxadiazole ring and the subsequent hydrolysis products were identified, but only in faeces, suggesting the involvement of gut bacteria. CONCLUSION: [14 C]-opicapone was fully excreted through multiple metabolic pathways. The main route of excretion was in faeces, where opicapone may be further metabolized via reductive metabolism involving the 1,2,4-oxadiazole ring-opening and subsequent hydrolysis.
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Inhibidores de Catecol O-Metiltransferasa , Oxadiazoles , Administración Oral , Inhibidores de Catecol O-Metiltransferasa/farmacocinética , Heces , Voluntarios Sanos , Humanos , Masculino , Oxadiazoles/farmacocinéticaRESUMEN
Swine genital leptospirosis is an infectious disease that leads to economic losses due to abortions, stillbirths, and reproductive failures. Considering the scarcity of studies regarding this condition, the objective of the present study was to identify and analyse leptospires infecting the reproductive tract of female pigs slaughtered in the Amazon region. Cervical-vaginal mucus (CVM) from 150 non-pregnant females were collected and submitted to molecular analysis. Initially, polymerase chain reaction (PCR) based on the lipL32 gene was performed. A total of 26.7% (40/150) samples were positive, indicating the presence of Leptospira sp. DNA. Subsequently, positive lipL32-PCR samples were evaluated using secY nested-PCR and sequencing procedures. Eleven amplicons could be sequenced and were identified as Leptospira interrogans (100% identity). Results from phylogenetic analyses led to identification of a putative strain of L. interrogans serogroup Australis, which is indicative of this being a serogroup. In the present study, there was detection of female pigs with leptospires in CVM indicating the possibility of venereal transmission. The large number of genital positive cases could indicate that genital leptospirosis syndrome could also be relevant onto swine production.
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Leptospira , Leptospirosis , Enfermedades de los Porcinos , Animales , Moco del Cuello Uterino , Femenino , Leptospira/genética , Leptospirosis/veterinaria , Filogenia , Embarazo , Porcinos , VaginaRESUMEN
Opicapone (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide) is a selective catechol-O-methyltransferase inhibitor that has been granted marketing authorization in Europe, Japan, and United States. The present work describes the metabolism and disposition of opicapone in the rat obtained in support to its development and regulatory filling. Plasma levels and elimination of total radioactivity were determined after oral and intravenous administration of [14 C]-opicapone. The maximum plasma concentrations of opicapone-related radioactivity were reached at early time points followed by a gradual return to baseline with a biphasic elimination. Fecal excretion was the primary route of elimination of total radioactivity. Quantitative distribution of drug-related radioactivity demonstrated that opicapone and related metabolites did not distribute to the central nervous system. Opicapone was extensively metabolized in rats resulting in more than 20 phase I and phase II metabolites. Although O-glucuronidation, -sulfation, and -methylation of the nitrocatechol moiety were the principal metabolic pathways, small amount of the N-acetyl derivative was detected, as a result of reduction of the nitro group and subsequent conjugation. Other metabolic transformations included N-oxide reduction to the pyridine derivative and reductive cleavage of 1,2,4-oxadiazole ring followed by further conjugative reactions. Reaction phenotyping studies suggested that SULT 1A1*1 and *2 and UGT1A7, UGT1A8, UGT1A9, and UGT1A10 may be involved in opicapone sulfation and glucuronidation, respectively. However, the reductive metabolic pathways mediated by gut microflora cannot be excluded. Opicapone, in the rat, was found to be rapidly absorbed, widely distributed to peripheric tissues, metabolized mainly via conjugative pathways at the nitro catechol ring, and primarily excreted via feces.
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Inhibidores de Catecol O-Metiltransferasa/farmacocinética , Oxadiazoles/farmacocinética , Administración Intravenosa , Administración Oral , Animales , Arilsulfotransferasa/metabolismo , Inhibidores de Catecol O-Metiltransferasa/administración & dosificación , Glucuronosiltransferasa/metabolismo , Masculino , Oxadiazoles/administración & dosificación , Fenotipo , Ratas , Ratas Wistar , Distribución TisularRESUMEN
People relate to nature physically, cognitively and emotionally, and this relationship fosters their well-being. There are several types of environments that vary according to their degree of naturalness, raising the question of whether they each exert different effects on people, connectedness and well-being. In order to study the extent to which environmental connectedness and well-being are a function of viewing different types of nature, we conducted a study with 454 participants from five different countries, who viewed images on a computer screen of one of three types of environment (totally natural, quasi-natural or non-natural) and responded to a series of associated items. The results of a mediation analysis showed an indirect effect of type of environment on well-being through positive and negative affect and connectedness to nature. The corresponding ANOVAs revealed differences in the connectedness and well-being elicited by different types of environment, and in preference: totally natural and quasi-natural environments (with no differences between them) showed differences with non-natural environments. Therefore, our study results suggest the usefulness of images of natural environments in fostering people's well-being and connectedness to nature.
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Ambiente , HumanosRESUMEN
OBJECTIVE: The aim of this study was to examine the test-retest reliability, internal consistency, and floor and ceiling effects of a Norwegian version of the Neurological Fatigue Index for Stroke (NFI-Stroke). METHOD: To evaluate the psychometric properties of the NFI-Stroke, persons with stroke were recruited. Inclusion criteria were: ≥18 years; a performance of ≥4 seconds on the Clock-Drawing Test; and participants had to speak and understand Norwegian. Test-retest reliability, internal consistency, and floor and ceiling effects were evaluated with Spearman's rho, Weighted Kappa, Cronbach's Alpha, corrected total-item correlation, percentage of the total score, and responses to each item. RESULT: Of 82 eligible, 66 respondents were included in the project. NFI-Stroke has a test-retest reliability of 0.89, 0.89, and 0.87 with Spearman's rho and 0.55-0.78 with Weighted Kappa. For the subgroup chronic stroke, Spearman's rho was 0.89, 0.86, and 0.93, and Weighted Kappa was 0.61-0.91. For the subgroup sub-acute stroke, Spearman's rho was 0.48, 0.55, and 0.51, and Weighted Kappa was 0.02-0.54. Cronbach's Alpha was 0.90. For the physical subscale, alpha was 0.89, and for the cognitive subscale 0.74. Corrected total-item correlation for NFI-Stroke was 0.50-0.78, 0.55-0.79 for the physical subscale, and 0.46-0.60 for the cognitive subscale. None scored the highest nor lowest possible score of the questionnaire. CONCLUSION: NFI-Stroke has high test-retest reliability, and high internal consistency with neither floor nor ceiling effects for persons with stroke. The questionnaire may be useful both in general rehabilitation in institutions as well as in the municipal health services.