Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents

In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties

Enzymatic degradation of starch thermoplastic blends using samples of different thickness

The material studied was a thermoplastic blend of corn starch with a poly(ethylene-vinyl alcohol) copolymer, SEVA-C. The influence of both the material’s exposed surface and enzyme concentration on degradation kinetics was studied. As α-amylase is present in the blood plasma, experiments were performed, varying the material thickness and the α-amylase between 50 and 100 units/l, at 37°C, lasting up to 90 days. Four different batches using SEVA-C and starch samples of different thickness were performed. The positive correlation between degradation rate and the exposed material surface was confirmed, since thin films with larger exposed surfaces were degraded faster than thick square plates having the same total mass. The degradation extent depends on the total amount of amorphous starch present in the formulation rather than on the amount of enzyme used and the minimum thickness to ensure maximum degradation was estimated to be close to 0.25 mm

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{μe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13  eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}

Phylogenetic relationships within Chamaecrista sect. Xerocalyx (Leguminosae, Caesalpinioideae) inferred from the cpDNA trnE-trnT intergenic spacer and nrDNA ITS sequences

Chamaecrista belongs to subtribe Cassiinae (Caesalpinioideae), and it comprises over 330 species, divided into six sections. The section Xerocalyx has been subjected to a profound taxonomic shuffling over the years. Therefore, we conducted a phylogenetic analysis using a cpDNA trnE-trnT intergenic spacer and nrDNA ITS/5.8S sequences from Cassiinae taxa, in an attempt to elucidate the relationships within this section from Chamaecrista. The tree topology was congruent between the two data sets studied in which the monophyly of the genus Chamaecrista was strongly supported. Our analyses reinforce that new sectional boundaries must be defined in the Chamaecrista genus, especially the inclusion of sections Caliciopsis and Xerocalyx in sect. Chamaecrista, considered here paraphyletic. The section Xerocalyx was strongly supported as monophyletic; however, the current data did not show C. ramosa (microphyllous) and C. desvauxii (macrophyllous) and their respective varieties in distinct clades, suggesting that speciation events are still ongoing in these specimens

Diagnostic Accuracy and Applicability of a PCR System for the Detection of Schistosoma mansoni DNA in Human Urine Samples from an Endemic Area

Schistosomiasis caused by Schistosoma mansoni, one of the most neglected human parasitoses in Latin America and Africa, is routinely confirmed by microscopic visualization of eggs in stool. The main limitation of this diagnostic approach is its lack of sensitivity in detecting individual low worm burdens and consequently data on infection rates in low transmission settings are little reliable. According to the scientific literature, PCR assays are characterized by high sensitivity and specificity in detecting parasite DNA in biological samples. A simple and cost effective extraction method for DNA of Schistosoma mansoni from urine samples in combination with a conventional PCR assay was developed and applied in an endemic area. This urine based PCR system was tested for diagnostic accuracy among a population of a small village in an endemic area, comparing it to a reference test composed of three different parasitological techniques. The diagnostic parameters revealed a sensitivity of 100%, a specificity of 91.20%, positive and negative predictive values of 86.25% and 100%, respectively, and a test accuracy of 94.33%. Further statistical analysis showed a k index of 0.8806, indicating an excellent agreement between the reference test and the PCR system. Data obtained from the mouse model indicate the infection can be detected one week after cercariae penetration, opening a new perspective for early detection and patient management during this stage of the disease. The data indicate that this innovative PCR system provides a simple to handle and robust diagnostic tool for the detection of S. mansoni DNA from urine samples and a promising approach to overcome the diagnostic obstacles in low transmission settings. Furthermore the principals of this molecular technique, based on the examination of human urine samples may be useful for the diagnosis of other neglected tropical diseases that can be detected by trans-renal DNA

Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture in humans

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing. One Sentence Summary We provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues

Qualidade dos cuidados de enfermagem e satisfação do paciente atendido em um hospital de ensino

OBJECTIVES: assess the quality of nursing care, the patients' satisfaction and the correlation between both. METHOD: cross-sectional study, involving 275 patients hospitalized at a teaching hospital in the Central-West of Brazil. The data were collected through the simultaneous application of three instruments. Next, they were included in an electronic database and analyzed in function of the positivity, median value and Spearman's correlation coefficients. RESULTS: among the nursing care assessed, only two were considered safe - hygiene and physical comfort; nutrition and hydration - while the remainder were classified as poor. Nevertheless, the patients were satisfied with the care received in the domains assessed: technical-professional, confidence and educational. This can be justified by the weak to moderate correlation that was observed among these variables. CONCLUSION: Despite the quality deficit, the patients' satisfaction level with the nursing care received was high. These results indicate that the institution needs to center its objectives on a continuing evaluation system of the care quality, aiming to attend to the patients' expectations.OBJETIVOS: evaluar la calidad de los cuidados de enfermería, la satisfacción del paciente y la correlación entre ambos. MÉTODO: estudio trasversal con 275 pacientes internados en un hospital de enseñanza de la región Centro-Oeste de Brasil. Los datos fueron recolectados mediante la aplicación simultánea de tres instrumentos. A seguir, fueron digitalizados en un banco de datos electrónico y analizados en función de la positividad, valor de mediana y coeficientes de correlación de Spearman. RESULTADOS: entre los cuidados de enfermería evaluados, solamente dos fueron considerados seguros - higiene y conforto físico; nutrición e hidratación - y los demás clasificados como pobres. Sin embargo, los pacientes se mostraron satisfechos con los cuidados recibidos en los dominios evaluados: técnico-profesional, confianza y educacional. Eso puede ser justificado por la correlación débil a moderada observada entre esas variables. CONCLUSIÓN: A pesar del déficit de cualidad, fue encontrado alto nivel de satisfacción de los pacientes con los cuidados de enfermería recibidos. Tales resultados indican la necesidad de que la institución centre sus objetivos en un sistema de evaluación permanente de la cualidad del cuidado, visando atender a las expectativas de los pacientes.OBJETIVOS: avaliar a qualidade dos cuidados de enfermagem, a satisfação do paciente e a correlação entre ambos. MÉTODO: estudo transversal, realizado com 275 pacientes internados em um hospital de ensino da Região Centro-Oeste do Brasil. Os dados foram obtidos por meio da aplicação simultânea de três instrumentos. A seguir, foram digitados em banco de dados eletrônico e analisados em função da positividade, valor de mediana e coeficientes de correlação de Spearman. RESULTADOS: dentre os cuidados de enfermagem avaliados, apenas dois foram considerados seguros - higiene e conforto físico; nutrição e hidratação - e os demais foram classificados como pobres. Todavia, os pacientes mostraram-se satisfeitos com os cuidados recebidos nos domínios avaliados: técnico-profissional, confiança e educacional. Isso pode ser justificado pela correlação fraca a moderada observada entre essas variáveis. CONCLUSÃO: apesar do déficit de qualidade, houve alto nível de satisfação dos pacientes com os cuidados de enfermagem recebidos. Tais resultados apontam a necessidade de a instituição centrar seus objetivos num sistema de avaliação permanente da qualidade do cuidado, visando o atendimento das expectativas dos pacientes