1,306 research outputs found
The existence of nursing in caring for terminally ills’life: a phenomenological study
By taking care of cancer patients in their process of end of life, nursing experience situations of suffering before the anguish of others. This study aimed to understand the meaning and significance attributed by the nurses from the palliative care cancer hospital. This is a phenomenological research, grounded in Heidegger’s thinking, performed with 13 nurses, who work at Oncology hospitalward, through semi-structured interviews, which were analyzed according to the steps recommended by Josgrilberg. From understanding the statementsof the subjects, two ontological themesemerged: Feeling satisfaction and love in the care offered and Feeling anger and inabilitytowards terminally ill patients.We inferred that working in Oncology Ward is something rewarding for these professionals, but it entails physical and mental suffering, from feeling helpless before the death-dying process. Thus, we showedthat nursing professionals need to be recognized as human beings and as such, also deserving of care
Platinum-Triggered Bond-Cleavage of Pentynoyl Amide and N-Propargyl Handles for Drug-Activation.
The ability to create ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous target-specific triggers offers the potential for traceless release of active drugs on tumor sites from antibody-drug conjugates (ADCs) and caged prodrugs. We have developed a metal-mediated bond-cleavage reaction that uses platinum complexes [K2PtCl4 or Cisplatin (CisPt)] for drug activation. Key to the success of the reaction is a water-promoted activation process that triggers the reactivity of the platinum complexes. Under these conditions, the decaging of pentynoyl tertiary amides and N-propargyls occurs rapidly in aqueous systems. In cells, the protected analogues of cytotoxic drugs 5-fluorouracil (5-FU) and monomethyl auristatin E (MMAE) are partially activated by nontoxic amounts of platinum salts. Additionally, a noninternalizing ADC built with a pentynoyl traceless linker that features a tertiary amide protected MMAE was also decaged in the presence of platinum salts for extracellular drug release in cancer cells. Finally, CisPt-mediated prodrug activation of a propargyl derivative of 5-FU was shown in a colorectal zebrafish xenograft model that led to significant reductions in tumor size. Overall, our results reveal a new metal-based cleavable reaction that expands the application of platinum complexes beyond those in catalysis and cancer therapy.EPSRC studentship for Benjamin Stenton
Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.
Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form
Magnetic Coupling in the Quiet Solar Atmosphere
Three kinds of magnetic couplings in the quiet solar atmosphere are
highlighted and discussed, all fundamentally connected to the Lorentz force.
First the coupling of the convecting and overshooting fluid in the surface
layers of the Sun with the magnetic field. Here, the plasma motion provides the
dominant force, which shapes the magnetic field and drives the surface dynamo.
Progress in the understanding of the horizontal magnetic field is summarized
and discussed. Second, the coupling between acoustic waves and the magnetic
field, in particular the phenomenon of wave conversion and wave refraction. It
is described how measurements of wave travel times in the atmosphere can
provide information about the topography of the wave conversion zone, i.e., the
surface of equal Alfv\'en and sound speed. In quiet regions, this surface
separates a highly dynamic magnetic field with fast moving magnetosonic waves
and shocks around and above it from the more slowly evolving field of high-beta
plasma below it. Third, the magnetic field also couples to the radiation field,
which leads to radiative flux channeling and increased anisotropy in the
radiation field. It is shown how faculae can be understood in terms of this
effect. The article starts with an introduction to the magnetic field of the
quiet Sun in the light of new results from the Hinode space observatory and
with a brief survey of measurements of the turbulent magnetic field with the
help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the
Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and
Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200
Mapping Patent Classifications: Portfolio and Statistical Analysis, and the Comparison of Strengths and Weaknesses
The Cooperative Patent Classifications (CPC) jointly developed by the
European and US Patent Offices provide a new basis for mapping and portfolio
analysis. This update provides an occasion for rethinking the parameter
choices. The new maps are significantly different from previous ones, although
this may not always be obvious on visual inspection. Since these maps are
statistical constructs based on index terms, their quality--as different from
utility--can only be controlled discursively. We provide nested maps online and
a routine for portfolio overlays and further statistical analysis. We add a new
tool for "difference maps" which is illustrated by comparing the portfolios of
patents granted to Novartis and MSD in 2016.Comment: Scientometrics 112(3) (2017) 1573-1591;
http://link.springer.com/article/10.1007/s11192-017-2449-
Adaptation and validation of the Inventory of family protective factors for the portuguese culture
Aim: Describe the process of cultural adaptation and validation of Inventory of Family Protective Factors (IFPF) for portuguese culture. This instrument assesses the protective factors that contribute to family resilience. Studies of resilience fall the salutogenic paradigm, which focuses on protective factors of individuals or groups, without minimizing the risk factors and vulnerability. Methods: We applied this instrument to 85 families of children with special needs and, after linguistic and conceptual equivalence, used an exploratory factor analysis with principal components analysis (with varimax rotation) and calculated the Cronbach's alpha coefficient for each dimension. Results: adequate psychometric properties to be used in Portuguese population (Cronbach´s alpha =.90). Conclusion: IFPF is an useful instrument for studies which propose assess the protective factors of family resilience, however we suggest further studies of revalidation.Objetivo: Describir el proceso de adaptación cultural y validación para la cultura portuguesa de Inventory of Family Protective Factors (IFPF). Este instrumento evalúa los factores de protección que contribuyan a la resiliencia familiar. Estudios de resiliência familiar se apoyan en el paradigma salutogénico, que se centra en los factores de protección de individuos o grupos, sin subestimar los factores de riesgo y vulnerabilidad. Metodologia: Aplicamos este instrumento a 85 familias de niños con necesidades especiales y, después de la equivalencia lingüística y conceptual, hemos llevado a cabo un análisis factorial exploratorio de componentes principales con rotación varimax y calculamos el coeficiente alfa de Cronbach. Resultados: la IFPF tiene adecuadas propiedades psicométricas para la población portuguesa (alfa de Cronbach = .90). Conclusion: Esta es una herramienta útil para evaluar los factores protectores de la resiliencia familiar, sin embargo sugerimos estudios futuros de revalidación.Objetivos: adaptar e validar o Inventory of Family Protective Factors (IFPF) para a cultura portuguesa. Este instrumento avalia os fatores protetores que contribuem para a resiliência familiar. Os estudos sobre resiliência inserem-se no paradigma salutogénico, abordando os fatores protetores dos indivíduos ou grupos, sem subestimar os fatores de risco ou vulnerabilidade. Método: para avaliar a equivalência linguística e conceitual do IFPF realizamos a tradução, retroversão e reflexão falada; para aferir as características psicométricas do instrumento verificamos a sensibilidade, confiabilidade e a validade dos resultados. Realizamos uma análise fatorial de componentes principais com rotação varimax dos itens da escala e calculamos o coeficiente Alpha de Cronbach para cada dimensão. Através de uma amostragem aleatória simples, aplicamos este instrumento a 85 famílias de crianças com necessidades especiais que o auto-preencheram. Resultados: o IFPF apresenta características psicométricas adequadas para a população portuguesa (alfa de Cronbach de .90). Conclusão: o IFPF foi adaptado e validado para a cultura portuguesa. Consideramos tratar-se de um instrumento útil para estudos que se proponham avaliar os fatores protetores da resiliência familiar
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions
Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
- …