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Abstract INTRODUCTION: Inadequate wastewater treatment and fecal contamination have a strong environmental impact on antimicrobial resistance (AMR). This study evaluated the profile of AMR enterobacteria and fecal contamination from four surface waters: Jiquiriça-Brejões River and Cabrito, Tororó, and Abaeté Lagoons. METHODS: We analyzed AMR β-lactamase genes using the polymerase chain reaction method and fecal contamination using Coliscan®. RESULTS: We found high levels of fecal contamination, β-lactamase producers, and AMR genes (blaOXA-48, blaSPM, and blaVIM) in all waterbodies. CONCLUSIONS: Poor sanitation evidenced by fecal contamination and human activities around these surface waters contributed to the distribution and increase in AMR enterobacteria.

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fatal cerebral edema. This novel syndrome has been designated immune effector cell–associated neurotoxicity syndrome (ICANS). In this review, we draw an arc from our current understanding of how systemic and potentially local cytokine release act on the CNS, toward possible preventive and therapeutic approaches. We systematically review reported correlations of secreted inflammatory mediators in the serum/plasma and cerebrospinal fluid with the risk of ICANS in patients receiving CAR T cell therapy. Possible pathophysiologic impacts on the CNS are covered in detail for the most promising candidate cytokines, including IL-1, IL-6, IL-15, and GM-CSF. To provide insight into possible final common pathways of CNS inflammation, we place ICANS into the context of other systemic inflammatory conditions that are associated with neurologic dysfunction, including sepsis-associated encephalopathy, cerebral malaria, thrombotic microangiopathy, CNS infections, and hepatic encephalopathy. We then review in detail what is known about systemic cytokine interaction with components of the neurovascular unit, including endothelial cells, pericytes, and astrocytes, and how microglia and neurons respond to systemic inflammatory challenges. Current therapeutic approaches, including corticosteroids and blockade of IL-1 and IL-6 signaling, are reviewed in the context of what is known about the role of cytokines in ICANS. Throughout, we point out gaps in knowledge and possible new approaches for the investigation of the mechanism, prevention, and treatment of ICANS.

The search for greater efficiency in the thermal performance of buildings in hot climate places aims to improve living conditions so as to mitigate extreme climatic conditions and to reduce energy consumption with artificial air conditioning. In this sense, thermal comfort evaluations aim to diagnose the environmental conditions offered to users in order to identify existing problems, and propose solutions for them. These evaluations are even more important in school environments, where this influence becomes more considerable due to the direct contribution of the thermal environment in the delicate teaching-learning relationship. This research is a study carried out in the city of Cajazeiras, located in Paraíba, it evaluated the thermal performance of the Instituto Federal de Educação, Ciência e Tecnologia da Paraíba, Cajazeiras campus classrooms. First of all, it tried to analyze local climatic conditions based on the test reference year - TRY calculated on the Instituto Nacional de Meteorologia meteorological station, located in São Gonçalo city / PB, 30km from Cajazeiras. Then, we described the physical characteristics of the classroom blocks, as well as the monitoring of four classrooms, which represented the two existing typologies, from October 11 to 24, 2016. It was found that the classrooms kept the temperature values within the zone of thermal comfort during class times, with the aid of the air conditioner. However, relative air humidity values were lower than the 60% limit suggested by the World Health Organization.

Talento de barrio, el filme puertorriqueño más taquillero de la historia, tiene como protagonista a Édgar, un maleante interpretado por la superestrella del reguetón Daddy Yankee. Mediante el contraste entre Édgar y otros personajes claramente antisociales, la película parece apuntar a la posibilidad del bandido social como una figura al margen de la legalidad, pero de signo positivo. Este ensayo recurre a autores como Hobsbawm, Benjamin, Agamben y otros para explorar el resurgimiento de un cierto tipo de bandidaje social, vinculado al narcotráfico y a la violencia extrema que conlleva, en la imaginación cinematográfica latinoamericana de hoy.

The relationship between poor sanitation and the parasitic infection schistosomiasis is well-known, but still rarely investigated directly and quantitatively. In a Brazilian village we correlated the spatial concentration of human fecal contamination of its main river and the prevalence of schistosomiasis.We validated three bacterial markers of contamination in this population by high throughput sequencing of the 16S rRNA gene and qPCR of feces from local residents. The qPCR of genetic markers from the 16S rRNA gene of Bacteroides-Prevotella group, Bacteroides HF8 cluster, and Lachnospiraceae Lachno2 cluster as well as sequencing was performed on georeferenced samples of river water. Ninety-six percent of residents were examined for schistosomiasis.Sequence of 16S rRNA DNA from stool samples validated the relative human specificity of the HF8 and Lachno 2 fecal indicators compared to animals. The concentration of fecal contamination increased markedly along the river as it passed an increasing proportion of the population on its way downstream as did the sequence reads from bacterial families associated with human feces. Lachnospiraceae provided the most robust signal of human fecal contamination. The prevalence of schistosomiasis likewise increased downstream. Using a linear regression model, a significant correlation was demonstrated between the prevalence of S. mansoni infection and local concentration of human fecal contamination based on the Lachnospiraceae Lachno2 cluster (r2 0.53) as compared to the correlation with the general fecal marker E. coli (r2 0.28).Fecal contamination in rivers has a downstream cumulative effect. The transmission of schistosomiasis correlates with very local factors probably resulting from the distribution of human fecal contamination, the limited movement of snails, and the frequency of water contact near the home. In endemic regions, the combined use of human associated bacterial markers and GIS analysis can quantitatively identify areas with risk for schistosomiasis as well as assess the efficacy of sanitation and environmental interventions for prevention.

Los isangos (Trombicula autumnalis) son conocidos popularmente en la selva peruana pero no se ha documentado su frecuencia. Se realizó un estudio transversal en un caserío de Lamas, región San Martín, se evaluó a 18 menores de cinco años los cuales todos tenían lesiones producidas por isangos, estos ejemplares fueron remitidos al Instituto Nacional de Salud los cuales fueron identificados como T. autumnalis. Se evaluó también a escolares y población adulta de esa localidad encontrando que 56/70 niños y 85/130 adultos tenían lesiones compatibles por infestación con T. autumnalis. Las zonas más afectadas fueron las piernas, ingle y nalg

Rituximab, a monoclonal antibody targeting CD20 on B cells, is currently used to treat many subtypes of B cell lymphomas. However, treatment is not curative and response rates are variable. Recombinant interleukin-21 (rIL-21) is a cytokine that enhances immune effector function and affects both primary and transformed B cell differentiation. We hypothesized that the combination of rIL-21 plus rituximab would be a more efficacious treatment for B cell malignancies than rituximab alone. We cultured human and cynomolgus monkey NK cells with rIL-21 and found that their activity was increased and proteins associated with antibody dependent cytotoxicity were up-regulated. Studies in cynomolgus monkeys modeled the effects of rIL-21 on rituximab activity against CD20 B cells. In these studies, rIL-21 activated innate immune effectors, increased ADCC and mobilized B cells into peripheral blood. When rIL-21 was combined with rituximab, deeper and more durable B cell depletion was observed. In another series of experiments, IL-21 was shown to have direct antiproliferative activity against a subset of human lymphoma cell lines, and combination of murine IL-21 with rituximab yielded significant survival benefits over either agent alone in xenogeneic mouse tumor models of disseminated lymphoma. Therefore, our results do suggest that the therapeutic efficacy of rituximab may be improved when used in combination with rIL-21.

The symptoms of multiple sclerosis (MS) are determined by the location of demyelinating lesions in the white matter of the brain and spinal cord. Currently, magnetic resonance imaging (MRI) is the most common tool used for diagnosing MS, understanding the course of the disease, and analyzing the effects of treatments. However, undesirable components may appear during the generation of MRI scans, such as noise or intensity variations. Mathematical morphology (MM) is a powerful image analysis technique that helps to filter the image and extract relevant structures. Granulometry is an image measurement tool for measuring MM that determines the size distribution of objects in an image without explicitly segmenting each object. While several methods have been proposed for the automatic segmentation of MS lesions in MRI scans, in some cases, only simple data preprocessing, such as image resizing to standardize the input dimensions, has been performed before the algorithm training. Therefore, this paper proposes an MRI preprocessing algorithm capable of performing elementary morphological transformations in brain images of MS patients and healthy individuals in order to delete undesirable components and extract the relevant structures such as MS lesions. Also, the algorithm computes the granulometry in MRI scans to describe the size qualities of lesions. Using this algorithm, we trained two artificial neural networks (ANNs) to predict MS diagnoses. By computing the differences in granulometry measurements between an image with MS lesions and a reference image (without lesions), we determined the size characterization of the lesions. Then, the ANNs were evaluated with the validation set, and the performance results (test accuracy = 0.9753; cross-entropy loss = 0.0247) show that the proposed algorithm can support specialists in making decisions to diagnose MS and estimating the disease progress based on granulometry values.

Interferon-beta is one of the most widely prescribed disease-modifying therapies for multiple sclerosis patients. However, this treatment is only partially effective, and a significant proportion of patients do not respond to this drug. This paper proposes an alternative fuzzy logic system, based on the opinion of a neurology expert, to classify relapsing–remitting multiple sclerosis patients as high, medium, or low responders to interferon-beta. Also, a pipeline prediction model trained with biomarkers associated with interferon-beta responses is proposed, for predicting whether patients are potential candidates to be treated with this drug, in order to avoid ineffective therapies. The classification results showed that the fuzzy system presented 100% efficiency, compared to an unsupervised hierarchical clustering method (52%). So, the performance of the prediction model was evaluated, and 0.8 testing accuracy was achieved. Hence, a pipeline model, including data standardization, data compression, and a learning algorithm, could be a useful tool for getting reliable predictions about responses to interferon-beta.

This paper proposes a deep learning model based on an artificial neural network with a single hidden layer for predicting the diagnosis of multiple sclerosis. The hidden layer includes a regularization term that prevents overfitting and reduces the model complexity. The purposed learning model achieved higher prediction accuracy and lower loss than four conventional machine learning techniques. A dimensionality reduction method was used to select the most relevant features from 74 gene expression profiles for training the learning models. The analysis of variance test was performed to identify the statistical difference between the mean of the proposed model and the compared classifiers. The experimental results show the effectiveness of the proposed artificial neural network.

Atacicept, a soluble recombinant fusion protein of the human immunoglobulin (Ig) G1 Fc and the extracellular domain of the human transmembrane activator and calcium modulator and cyclophylin ligand interactor receptor, acts as an antagonist of both B lymphocyte stimulator and a proliferating–inducing ligand. Here we determined the nonclinical safety, pharmacokinetics and pharmacodynamics of atacicept in mice and cynomolgus monkeys. Subcutaneous atacicept treatment (twice weekly in cynomolgus monkeys, three times weekly in mice) was generally safe and well tolerated safe and well tolerated with dosing up to 10 mg/kg every other day for up to 39 weeks or up to 80 mg/kg when dosed for 4 weeks. At a dose of 1 mg/kg subcutaneous (sc) bioavailability of atacicept in mice and monkeys was 76 and 92%, with a mean serum t1/2 of 44 and 179 h, respectively. In accord with its anticipated mechanism of action, repeated administration of atacicept decreased serum IgG concentrations up to 50%, IgM concentrations >99%, and circulating mature B-cell concentrations up to 60%. These effects were dose-related but reversible, as determined in a 25-week follow-up period. Microscopically, B cells numbers were reduced in the follicular marginal zone of the spleen and the mantle surrounding germinal centers of the lymph nodes. These data confirm the preclinical safety and the pharmacological activity of atacicept and support its clinical development. [ABSTRACT FROM AUTHOR]