CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4-866.3). NOTCH1 mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRAS mut and FBXW7 mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL

DIAGNÓSTICOS E INTERVENÇÕES DE ENFERMAGEM PARA IDOSOS DEPRIMIDOS E RESIDENTES EM UMA INSTITUIÇÃO DE LONGA PERMANÊNCIA (ILP)

The objectives of the study are to identify depression; to propose actions in nursing that could be implemented to minimize or/and prevent signs and symptoms of depression in elderly living in a long term stay institution (ILE). Exploratory descriptive study with a qualitative approach, using as a sample one ILE of the city of R&iacute;o Grande, Rio Grande do Sul, Brazil. The subjects studied were 55 elderly people. Two instruments to collect data were used. The application of the instruments was carried out after project approval, following the directions of Resolution 196/96. The results obtained were: elderly people between 60 and 105 years of age, being of female sex, widows followed by singles, born in Rio Grand and retired. A number of twenty elderly people presented depression and six of them borderline affective disorders. Nursing actions were focused on diagnosing impotence feelings, loss of hope, risk of loneliness, perturbed thinking process, increased disposition for spiritual well being, revealing that the elderly people feel happy and satisfied with life in spite of institutionalization. In this way, the implemented activities are providing the elderly people joy, participation and social coexistence with other people.Este estudio tuvo como objetivos: identificar la depresi&oacute;n; proponer acciones de enfermer&iacute;a que podr&aacute;n ser realizados para minimizaci&oacute;n y/o prevenci&oacute;n de se&ntilde;ales y s&iacute;ntomas de depresi&oacute;n en los ancianos residentes en una Instituci&oacute;n de Larga Estancia (ILE). Estudio exploratorio descriptivo con abordaje cualitativo, teniendo como local una ILE de la ciudad de R&iacute;o Grande, Rio Grande do Sul, Brasil. Los sujetos de estudio totalizaron 55 ancianos. Fueron utilizados dos instrumentos de colecta de datos. La aplicaci&oacute;n de los instrumentos se efectu&oacute; despu&eacute;s de la aprobaci&oacute;n del proyecto, siguiendo las orientaciones de la Resoluci&oacute;n 196/96. Se obtuvieron, como resultados: la edad de los ancianos entre 60 a 105 a&ntilde;os, siendo predominante el sexo femenino, viudos seguidos por solteros, nacidos en R&iacute;o Grande y jubilados. Veinte ancianos presentaron depresi&oacute;n y seis de ellos trastornos afectivos lim&iacute;trofes. Las acciones de enfermer&iacute;a se concentraron en los diagn&oacute;sticos de Sentimiento de impotencia, Desesperanza, Riesgo para la soledad, Proceso de pensamiento perturbado, Disposici&oacute;n para el bienestar espiritual aumentado, revelando que los ancianos se sienten felices y satisfechos con la vida, a pesar de la institucionalizaci&oacute;n. De esta forma, constato, que las actividades implementadas ya est&aacute;n proporcionando a los ancianos, alegr&iacute;a y participaci&oacute;n y convivencia social con otras personas.Este estudo teve como objetivos: identificar a depress&atilde;o; propor a&ccedil;&otilde;es de enfermagem que poder&atilde;o ser realizadas para minimiza&ccedil;&atilde;o e/ou preven&ccedil;&atilde;o de sinais e sintomas de depress&atilde;o em idosos residentes em uma Institui&ccedil;&atilde;o de Longa Perman&ecirc;ncia (ILP). Estudo de car&aacute;ter explorat&oacute;rio-descritivo com abordagem qualitativa, tendo como local uma ILP da cidade de Rio Grande, Rio Grande do Sul, Brasil. Os sujeitos do estudo totalizaram 55 idosos. Foram utilizados dois instrumentos de coleta dos dados, cuja aplica&ccedil;&atilde;o efetivou-se ap&oacute;s aprova&ccedil;&atilde;o do projeto e seguindo as orienta&ccedil;&otilde;es da Resolu&ccedil;&atilde;o 196/96. Resultados: a idade dos idosos variou entre 60 a 105 anos, predominado o sexo feminino, vi&uacute;vos seguidos por solteiros, nascidos em Rio Grande e aposentados. Vinte idosos apresentaram depress&atilde;o e seis deles transtorno afetivo lim&iacute;trofe. As a&ccedil;&otilde;es de enfermagem voltaram-se para os diagn&oacute;sticos de enfermagem de Sentimento de impot&ecirc;ncia, Desesperan&ccedil;a, Risco de solid&atilde;o, Processo de pensamento perturbado, Disposi&ccedil;&atilde;o para bem-estar espiritual aumentado, revelando que os idosos se sentem felizes e satisfeitos com a vida, apesar da institucionaliza&ccedil;&atilde;o. Desta forma, constata-se que as atividades implementadas est&atilde;o proporcionando aos idosos, alegria, participa&ccedil;&atilde;o e conv&iacute;vio social com outras pessoas

Trade-offs during the COVID-19 pandemic: A discrete choice experiment about policy preferences in Portugal

The need to control the sanitary situation during the COVID-19 pandemic has led governments to implement several restrictions with substantial social and economic impacts. We explored people’s trade-offs in terms of their income, life restrictions, education, and poverty in the society, compared to their willingness to avoid deaths. We applied a web-based discrete choice experiment to elicit preferences of the Portuguese citizens for these attributes and computed the marginal rate of substitution in terms of avoided deaths. We recorded 2,191 responses that faced the possibility of having 250 COVID-19 related deaths per day as the worst possible outcome from the choice levels presented. Estimates suggested that individuals would be willing to sacrifice 30% instead of 10% of their income to avoid approximately 47 deaths per day during the first six months of 2021. For the same period, they would also accept 30% of the students’ population to become educationally impaired, instead of 10%, to avoid approximately 25 deaths; a strict lockdown, instead of mild life restrictions, to avoid approximately 24 deaths; and 45% of the population to be in risk of poverty, instead of 25%, to avoid approximately 101 deaths. Our paper shows that avoiding deaths was strongly preferred to the remaining societal impacts; and that being a female, as well as working on site, led individuals to be more averse to such health hazards. Furthermore, we show how a DCE can be used to assess the societal support to decision-making during times of crisis

Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents

Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (-)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p &lt; 0.001), BOR and CIT in all doses (p &lt; 0.05 or p &lt; 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p &lt; 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.Key words: Carvacrol, (-)-borneol, citral, anticonvulsant activit

The Environmental History of Cetaceans in Portugal: Ten Centuries of Whale and Dolphin Records

The history between cetaceans and humans is documented throughout time not only in reports, descriptions, and tales but also in legal documents, laws and regulations, and tithes. This wealth of information comes from the easy spotting and identification of individuals due to their large size, surface breathing, and conspicuous above water behaviour. This work is based on historical sources and accounts accounting for cetacean presence for the period between the 12th and 17th centuries, as well as scientific articles, newspapers, illustrations, maps, non-published scientific reports, and other grey literature from the 18th century onwards. Information on whale use in Portugal's mainland has been found since as early as the 12th century and has continued to be created throughout time. No certainty can be given for medieval and earlier events, but both scavenging of stranded whales or use of captured ones may have happened. There is an increasing number of accounts of sighted, stranded, used, or captured cetaceans throughout centuries which is clearly associated with a growing effort towards the study of these animals. Scientific Latin species denominations only started to be registered from the 18th century onwards, as a consequence of the evolution of natural sciences in Portugal and increasing interest from zoologists. After the 19th century, a larger number of observations were recorded, and from the 20th century to the present day, regular scientific records have been collected. Research on the environmental history of cetaceans in Portugal shows a several-centuries-old exploitation of whales and dolphins, as resources mainly for human consumption, followed in later centuries by descriptions of natural history documenting strandings and at sea encounters. Most cetaceans species currently thought to be present in Portuguese mainland waters were at some point historically recorded

Converting simulated total dry matter to fresh marketable yield for field vegetables at a range of nitrogen supply levels

Simultaneous analysis of economic and environmental performance of horticultural crop production requires qualified assumptions on the effect of management options, and particularly of nitrogen (N) fertilisation, on the net returns of the farm. Dynamic soil-plant-environment simulation models for agro-ecosystems are frequently applied to predict crop yield, generally as dry matter per area, and the environmental impact of production. Economic analysis requires conversion of yields to fresh marketable weight, which is not easy to calculate for vegetables, since different species have different properties and special market requirements. Furthermore, the marketable part of many vegetables is dependent on N availability during growth, which may lead to complete crop failure under sub-optimal N supply in tightly calculated N fertiliser regimes or low-input systems. In this paper we present two methods for converting simulated total dry matter to marketable fresh matter yield for various vegetables and European growth conditions, taking into consideration the effect of N supply: (i) a regression based function for vegetables sold as bulk or bunching ware and (ii) a population approach for piecewise sold row crops. For both methods, to be used in the context of a dynamic simulation model, parameter values were compiled from a literature survey. Implemented in such a model, both algorithms were tested against experimental field data, yielding an Index of Agreement of 0.80 for the regression strategy and 0.90 for the population strategy. Furthermore, the population strategy was capable of reflecting rather well the effect of crop spacing on yield and the effect of N supply on product grading

The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

This is the final version (corrected proof). The final published version is available from Public Library of Science via the DOI in this recordData Availability: Short reads were submitted to the NCBI’s Sequence Read Archive under accession number SRP154617 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP154617). The ChIPseq data are available from NCBI SRA (sequence read archive) database under accession number PRJNA574873 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA574873&o=acc_s%3Aa).Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)Wellcome TrustUniversity of MacauNational Science Foundation (NSF)Vanderbilt UniversityHoward Hughes Medical Institut

Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-α, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this β-glucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen