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The nature of the immune responses associated with COVID‐19 pathogenesis and disease severity, as well as the breadth of vaccine coverage and duration of immunity, is still unclear. Given the unpredictability for developing a severe/complicated disease, there is an urgent need in the field for predictive biomarkers of COVID‐19. We have analyzed IgG Fc N‐glycan traits of 82 SARS‐CoV‐2+ unvaccinated patients, at diagnosis, by nano‐LC‐ESI‐MS. We determined the impact of IgG Fc glyco‐variations in the induction of NK cells activation, further evaluating the association between IgG Fc N‐glycans and disease severity/prognosis. We found that SARS‐CoV‐2+ individuals display, at diagnosis, variations in the glycans composition of circulating IgGs. Importantly, levels of galactose and sialic acid structures on IgGs are able to predict the development of a poor COVID‐19 disease. Mechanistically, we demonstrated that a deficiency on galactose structures on IgG Fc in COVID‐19 patients appears to induce NK cells activation associated with increased release of IFN‐γ and TNF‐α, which indicates the presence of pro‐ inflammatory immunoglobulins and higher immune activation, associated with a poor disease course. This study brings to light a novel blood biomarker based on IgG Fc glycome composition with capacity to stratify patients at diagnosis.

Purpose: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients’ health-related quality of life (HRQoL). Methods: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. Results: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms – lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (–4.646, 95% CI –6.953 to –2.339) and in the physical functioning (–9.622, 95% CI –17.061 to –2.183) and physical role functioning (–3.669, 95% CI –7.339 to 0.001) dimensions of the SF36. Conclusions: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.

To evaluate the diagnostic value of described thresholds of controlled attenuation parameter (CAP) and biomarker scores for liver steatosis and to evaluate new cut-offs to detect moderate-to-severe steatosis (S2–3) in patients with morbid obesity. In this prospective study, 32 patients with morbid obesity with indications for bariatric surgery (15 women and 17 men, mean age = 36 years, median BMI = 40.2 kg/m2) underwent CAP, magnetic resonance spectroscopy (MRS), three biomarker scores (Steato-ELSA, Fatty Liver Index (FLI), and Hepatic Steatosis Index (HSI)), and liver biopsy. Subjects were divided into an exploratory cohort (reliable CAP and liver biopsy) and a confirmatory cohort (reliable CAP and MRS) to evaluate new thresholds for CAP and biomarker scores to detect S2–3. Receiver operator characteristic (ROC) curves analyses were performed and the optimal cut-off points were identified using the maximal Youden index. A total of 22 patients had CAP measure and liver biopsy (exploratory cohort) and 24 patients had CAP measure with MRS (confirmatory cohort). New cut-offs were identified for detection of S2–3 by the non-invasive tests using liver biopsy as the reference standard (exploratory cohort). Considering the new proposed cut-offs for detection of S2–3 for CAP (≥ 314 dB/m), Steato-ELSA (≥ 0.832), FLI (≥ 96), and HSI (≥ 53), for the exploratory and confirmatory cohorts sensitivities were: 71–75%, 86–81%, 85–81%, and 71–69% and specificities were: 94–89%, 75–63%, 63–63%, and 75–88%, respectively. Higher cut-offs for CAP and biomarker scores may be better to diagnose moderate-to-severe steatosis in patients with morbid obesity.

α-Synuclein (αsyn) is a cytosolic intrinsically disordered protein (IDP) known to fold into an α-helical structure when binding to membrane lipids, decreasing protein aggregation. Model membrane enable elucidation of factors critically affecting protein folding/aggregation, mostly using either small unilamellar vesicles (SUVs) or nanodiscs surrounded by membrane scaffold proteins (MSPs). Yet SUVs are mechanically strained, while MSP nanodiscs are expensive. To test the impact of lipid particle size on α-syn structuring, while overcoming the limitations associated with the lipid particles used so far, we compared the effects of large unilamellar vesicles (LUVs) and lipid-bilayer nanodiscs encapsulated by diisobutylene/maleic acid copolymer (DIBMA) on αsyn secondary-structure formation, using human-, elephant- and whale -αsyn. Our results confirm that negatively charged lipids induce αsyn folding in h-αsyn and e-αsyn but not in w-αsyn. When a mixture of zwitterionic and negatively charged lipids was used, no increase in the secondary structure was detected at 45 °C. Further, our results show that DIBMA/lipid particles (DIBMALPs) are highly suitable nanoscale membrane mimics for studying αsyn secondary-structure formation and aggregation, as folding was essentially independent of the lipid/protein ratio, in contrast with what we observed for LUVs having the same lipid compositions. This study reveals a new and promising application of polymer-encapsulated lipid-bilayer nanodiscs, due to their excellent efficiency in structuring disordered proteins such as αsyn into nontoxic α-helical structures. This will contribute to the unravelling and modelling aspects concerning protein-lipid interactions and α-helix formation by αsyn, paramount to the proposal of new methods to avoid protein aggregation and disease. info:eu-repo/semantics/publishedVersion

Objectives: to validate nursing care effectiveness indicators of patient safety dimension. Methods: quantitative survey, using the electronic Delphi sampli, with 52 participants selected by the Snowball sampling. Eight indicators were evaluated regarding the attributes: availability, reliability, simplicity, representativeness, sensitivity, comprehensiveness, objectivity, cost, utility, stability and timeliness. For validation, the minimum agreement criterion was 70%. Results: Cronbach’s alpha (0.942) evidenced the high internal consistency among the attributes. The indicators fall with damage, hip fracture, and postoperative hip fracture, incidents related to equipment, incidents due to failures in patient identification, and pressure injury were validated in all attributes, and those of medication error and hand Hygiene were not validated. Conclusions: the validated indicators allow assessment of the effectiveness of hospital nursing care. Unavailability of data is an obstacle to monitoring patient safety. RESUMEN Objetivos: validar los indicadores de efectividad de la asistencia de enfermería hospitalaria en la dimensión seguridad del paciente. Métodos: estudio quantitativo, tipo survey, mediante la técnica Delphi electrónica, en el cual participaron 52 individuos seleccionados por la técnica Bola de Nieve. Se evaluaron ocho indicadores en los atributos disponibilidad, confiabilidad, sencillez, representatividad, sensibilidad, alcance, objetividad, costo, utilidad, estabilidad y tempestividad. El criterio mínimo de concordancia para validación fue del 70%. Resultados: el Alfa de Cronbach (0,942) evidenció la alta consistencia interna entre los atributos. Los indicadores caída con daño, fractura de cadera y fractura de cadera postoperatoria, incidentes relacionados con herramientas, incidentes debido a fallas en la identificación del paciente, y lesión por presión fueron validados en todos los atributos, y los de error de medicación y la higiene de las manos no han sido validados. Conclusiones: los indicadores validados permiten evaluar la efectividad asistencial de la enfermería. La indisponibilidad de datos es un obstáculo al monitoreo de la seguridad del paciente. RESUMO Objetivos: validar indicadores de efetividade da assistência de enfermagem hospitalar na dimensão segurança do paciente. Métodos: estudo quantitativo, tipo survey, mediante a técnica Delphi eletrônica, com 52 participantes selecionados pela técnica Bola de Neve. Oito indicadores foram avaliados quanto aos atributos disponibilidade, confiabilidade, simplicidade, representatividade, sensibilidade, abrangência, objetividade, custo, utilidade, estabilidade e tempestividade. Para validação o critério mínimo de concordância foi de 70%. Resultados: o alfa de Cronbach (0,942) evidenciou a alta consistência interna entre os atributos. Os indicadores queda com dano, fratura de quadril, e fratura de quadril pós-operatória, incidentes relacionados a equipamentos, incidentes devido a falhas na identificação do paciente, e lesão por pressão foram validados em todos os atributos, e os de erro de medicação e higiene de mãos não foram validados. Conclusões: os indicadores validados permitem avaliação da efetividade assistencial da enfermagem hospitalar. A indisponibilidade de dados é um óbice ao monitoramento da segurança do paciente.

The first contact of tannins with the human body occurs in the mouth, where some of these tannins are known to interact with salivary proteins, in particular with proline-rich proteins (PRPs). These interactions are important at a sensory level, especially for astringency development, but could also affect the biological activities of the tannins. This study gathers information on the relative affinity of the interaction, complex stoichiometry, and tannin molecular epitopes of binding for the interactions between the families of PRPs (bPRPs, gPRPs, and aPRPs) and three representative ellagitannins (castalagin, vescalagin, and punicalagin). These interactions were studied by saturation-tranfer difference NMR and microcalorimetry. The effect of the PRP-ellagitannin interaction on their antioxidant ability was also assessed by ferric reduction antioxidant power (FRAP) assays. The results support a significant interaction between the studied tannins and PRPs with binding affinities in the micromolar range. Punicalagin was always the ellagitannin with higher affinity. aPRPs were the salivary PRPs with higher affinity. Moreover, it was observed that when ellagitannins are present in low concentrations (5-50 μM), as occurs in food, the antioxidant ability of these tannins when complexed with salivary PRPs could be significantly impaired.

Laminin immobilization into diverse biological and synthetic matrices has been explored to replicate the microenvironment of stem cell niches and gain insight into the role of extracellular matrix (ECM) on stem cell behavior. However, the site-specific immobilization of this heterotrimeric glycoprotein and, consequently, control over its orientation and bioactivity has been a challenge that has limited many of the explored strategies to date. In this work, we established an affinity-based approach that takes advantage of the native high affinity interaction between laminin and the human N-terminal agrin (hNtA) domain. This interaction is expected to promote the site-selective immobilization of laminin to a specific substrate, while preserving the exposure of its key bioactive epitopes. Recombinant hNtA (rhNtA) domain was produced with high purity (>90%) and successfully conjugated at its N-terminal with a thiol-terminated poly(ethylene glycol) (PEG) without affecting its affinity to laminin. Self-assembled monolayers (SAMs) of mono-PEGylated rhNtA on gold (mPEG rhNtA-SAMs) were then prepared to evaluate the effectiveness of this strategy. The site-specific immobilization of laminin onto mPEG rhNtA-SAMs was shown to better preserve protein bioactivity in comparison to laminin immobilized on SAMs of thiol-PEG-succinimidyl glutaramide (HS-PEG-SGA), used for the non-selective covalent immobilization of laminin, as evidenced by its enhanced ability to efficiently self-polymerize and mediate cell adhesion and spreading of human neural stem cells. These results highlight the potential of this novel strategy to be used as an alternative to the conventional immobilization approaches in a wide range of applications, including engineered coatings for neuroelectrodes and cell culture, as well as biofunctionalization of 3D matrices. The mass spectrometry technique was performed at the Proteomics i3S Scientific Platform ( Roteiro/0028/2013 ; LISBOA-01-0145-FEDER-022125 ) with the assistance of Hugo Osório. IRRAS analysis was performed at the Biointerfaces and Nanotechnology Scientific Platform, with the assistance of Ricardo Vidal. In Cell Analyzer experiments were performed at the Biosciences Screening i3S Scientific Platform , member of the PPBI ( PPBI-POCI-01-0145-FEDER-022122 ) with the assistance of André Maia. Confocal microscopy was conducted at the Bioimaging i3S Scientific Platform , member of the PPBI ( PPBI-POCI-01-0145-FEDER-022122 ), with the assistance of Maria Lázaro. This work was supported by projects NORTE-01-0145-FEDER-000008 and NORTE-01-0145-FEDER-000012 , supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation ( POCI ), Portugal 2020; by Portuguese funds through FCT/MCTES in the framework of the project “Institute for Research and Innovation in Health Sciences” ( POCI-01-0145-FEDER-007274 ) and by project COMBINE (Santa Casa da Misericordia de Lisboa – Prémio Neurociências Mello e Castro). D.B. was supported by FCT PhD Programs ( PD/BD/105953/2014 ) and Programa Operacional Potencial Humano (POCH), in the scope of the BiotechHealth Program (Doctoral Program on Cellular and Molecular Biotechnology Applied to Health Sciences), Programa FLAD Helthcare 2020 and the project PARES (Prémio Albino Aroso). Eduardo Conde-Sousa was supported by a post-doctoral grant of the project PPBI-POCI-01-0145-FEDER-022122 , in the scope of Fundação para a Ciência e Tecnologia, Portugal (FCT) National Roadmap of Research Infrastructures. Appendix A

Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78.

Antimicrobial peptides (AMPs) are a class of broad-spectrum antibiotics known by their ability to disrupt bacterial membranes and their low tendency to induce bacterial resistance, arising as excellent candidates to fight bacterial infections. In this study we aimed at designing short 12-mer AMPs, derived from a highly effective and broad spectrum synthetic AMP, MSI-78 (22 residues), by truncating this peptide at the N- and/or C-termini while spanning its entire sequence with 1 amino acid (aa) shifts. These designed peptides were evaluated regarding antimicrobial activity against selected gram-positive Staphylococcus strains and the gram-negative Pseudomonas aeruginosa (P. aeruginosa). The short 12-mer peptide CEM1 (GIGKFLKKAKKF) was identified as an excellent candidate to fight P. aeruginosa infections as it displays antimicrobial activity against this strain and selectivity, with negligible toxicity to mammalian cells even at high concentrations. However, in general most of the short 12-mer peptides tested showed a reduction in antimicrobial activity, an effect that was more pronounced for gram-positive Staphylococcus strains. Interestingly, CEM1 and a highly similar peptide differing by only one aa-shift (CEM2: IGKFLKKAKKFG), showed a remarkably contrasting AMP activity. These two peptides were chosen for a more detailed study regarding their mechanism of action, using several biophysical assays and simple membrane models that mimic the mammalian and bacterial lipid composition. We confirmed the correlation between peptide helicity and antimicrobial activity and propose a mechanism of action based on the disruption of the bacterial membrane permeability barrier.

Monolithic columns have attracted significant attention for the purification of large biomolecules. In the present study, a step gradient elution method was evaluated for the separation of human immunoglobulin G (hIgG) into its subclasses on CIM (convective interaction media) Gamma-protein A (recombinant protein A) monolithic column. hIgG was loaded onto the column and bound protein was eluted with a pH gradient. The subclass content of the eluted fractions was analyzed by enzyme-linked immunosorbent assay (ELISA). Results showed that separation of IgG3 from the other three subclasses can be successfully achieved with high selectivity (100%) and throughput on monolithic media. It was also revealed that enriched fractions of IgG1 and IgG2 could be obtained from purified hIgG in a 28 min long chromatographic run. Three fractions with high IgG1 content (89.1%, 94.3% and 88.8%) were recovered. Furthermore, IgG2 was enriched to 64% successfully. A rapid step gradient elution scheme without any additives in buffers was proven to obtain enriched preparations of the two important subclasses with high throughput. The separation time can be reduced even more by increasing the flow rate without any loss in selectivity, which will be beneficial in industrial scale applications.

In this work, saturation transfer difference-NMR, isothermal microcalorimetry and molecular dynamics simulations have been used to study the individual interactions between basic, glycosylated and acidic proline-rich proteins (bPRPS, gPRPs, aPRPs) and P-B peptide with some representative food tannins [procyanidin B2, procyanidin B2 3'-O-gallate (B2g) and procyanidin trimer (catechin-4-8-catechin-4-8-catechin)]. Results showed that P-B peptide was in general the salivary protein (SP) with higher affinity whereas aPRPs showed lower affinity to the studied procyanidins. Moreover, B2g was the procyanidin with higher affinity for all SP. Hydrophobic and hydrogen bonds were present in all interactions but the major driving force depended on the procyanidin-SP pair. Furthermore, proline clusters or residues in their vicinity were identified as the probable sites of proteins for interaction with procyanidins. For bPRP and aPRP a significant change to less extended conformations was observed, while P-B peptide did not display any structural rearrangement upon procyanidins binding.

Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes.This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome.Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively.Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor involved in various human diseases, as it binds to numerous molecules and proteins that modulate the activity of other proteins. Elucidating the three-dimensional structure of this receptor is therefore most important for understanding its function during activation and cellular signaling. The major alternative splice product of RAGE comprises its extracellular region that occurs as a soluble protein (sRAGE). Although the structures of sRAGE domains were available, their assembly into the functional full-length protein remained unknown. We observed that the protein has concentration-dependent oligomerization behavior, and this is also mediated by the presence of Ca(2+) ions. Moreover, using synchrotron small angle x-ray scattering, the solution structure of human sRAGE was determined in the monomeric and dimeric forms. The model for the monomer displays a J-like shape, whereas the dimer is formed through the association of the two N-terminal domains and has an elongated structure. These results provide insights into the assembly of the RAGE homodimer, which is essential for signal transduction, and the sRAGE:RAGE heterodimer that leads to blockage of the receptor signaling, paving the way for the design of therapeutic strategies for a large number of different pathologies.

Summary Background and objectives The objective of this study was to review the literature and to question the concept that obese patients should be considered as having a potential full stomach and, therefore, question how the airways, considered as of difficult access due to obesity, should be approached during anesthetic induction. Contents Classically, obese patients are viewed as having a potential full stomach, leading to conducts to protect the airways during anesthetic induction. Frequently, awake intubation or rapid sequence intubation is performed. However, this concept is based on a single study, which has been cited by other authors. Obese patients are also considered difficult to intubate, raising the concern on the successful approach of the airways. However, studies in the literature question this concept, leading to questioning of the techniques used to access the airways. Conclusions Studies in the literature demonstrate that gastric emptying is not slowed in obese patients as previously believed, and gastric contents are not greater in this patient population; intubation can, therefore, be safely done after anesthesia. Although obesity alone does not lead to failure to intubate, other signs can be used to predict difficult intubations.

The study of the organizational commitment has risen interest within the organization's researchers, who have been trying to understand the intensity and stability of the individual's dedication to the organization. The interest that this construct has raised is based on the idea of the existence of an association of the organizational commitment with variables considered important to the increase of the organizational effectiveness and productivity. The aim of this article is to describe organizational commitment, in its affective, normative, and continuance dimensions, from nurse practitioners, and to analyze the differences of that commitment regarding gender. Data were collected by questionnaire. The sample is constituted by nurse practitioners who develop their professional activity in 6 Portuguese hospitals. Data were analyzed using means, standard deviation, and independent samples t test. The sample consists of 1201 nurses. The organizational commitment of the studied nurses is, on average, 2.87+/-0.69 (in 5-point scale). When we make an analysis regarding gender, we verify that the organizational commitment is higher in women, being the difference statistically significant (t = -2.07; P < .05). There are different levels of commitment in male and female nurses, and it is higher in all dimensions in female nurses; however, the difference is only significant to the organizational and continuance commitment.

Knowledge management imposes itself as a pressing need for the organizations of several sectors of the economy, including healthcare.to evaluate the perception of healthcare institution collaborators in relation to knowledge management in the institution where they operate and analyze the existence of differences in this perception, based on the institution's management model.a study conducted in a sample consisting of 671 collaborators from 10 Portuguese healthcare institutions with different models of management. In order to assess the knowledge management perception, we used a score designed from and based on items from the scores available in the literature.the perception of moderate knowledge management on the healthcare institutions and the statistically significant differences in knowledge management perception were evidenced in each management model.management knowledge takes place in healthcare institutions, and the current management model determines the way staff at these institutions manage their knowledge.

to perform the cultural adaptation to Portuguese of the Nursing Clinical Facilitators Questionnaire (NCFQ), which was designed by the Centre for Learning and Teaching at the University of Technology of Sydney, and to validate this instrument.this methodological study involved the cultural adaptation of the questionnaire by using translation, back-translation, semantic comparison, idiomatic and conceptual equivalence, and validation through validity and reliability analyses and used a sample of 767 students in their second year of the Nursing Program.construct validity had a two-factor solution according to the varimax rotation method. In addition, there was a high overall internal consistency for the questionnaire (Cronbach's alpha of 0.977) and for the factors found (0.966 and 0.952, respectively).the Portuguese version has good psychometric characteristics; therefore, it is adequate to obtain reliable information on the perception of nursing students concerning the type of supervision that is provided in clinical practice, and this version is adequate to improve teaching practices.realizar a adaptação cultural para a língua portuguesa do Nursing Clinical Facilitators Questionnaire (NCFQ) concebido pelo Centre for Learning and Teaching, University of Technology de Sydney e proceder à validação do instrumento.estudo metodológico de adaptação cultural do questionário através de tradução, retroversão, comparação semântica, idiomática e equivalência conceitual, seguido de validação em uma amostra de 767 estudantes do 2º ano do Curso de Licenciatura em Enfermagem, por meio de análise da validade e confiabilidade.a validade de constructo apresenta uma solução bifatorial após rotação varimax. A consistência interna global do questionário é elevada (alfa de Cronbach 0,977), assim como dos fatores encontrados (respectivamente, 0,966 e 0,952).a versão portuguesa apresenta boas características psicométricas, sendo um instrumento válido para obter informação fidedigna acerca da percepção dos estudantes de enfermagem relativamente ao tipo de orientação tida em contexto clínico, revelando-se importante para melhoria das práticas pedagógicas.llevar a cabo la adaptación cultural al portugués del Nursing Clinical Facilitators Questionnaire (NCFQ), diseñado por el Centre for Learning and Teaching, University of Technology Sydney, y validar este instrumento.este estudio metodológico implicó la adaptación cultural del cuestionario usando la traducción, la retrotraducción, la comparación semántica, la equivalencia idiomática y conceptual, y la validación usando una muestra de 767 estudiantes del segundo curso del Programa de Enfermería mediante análisis de validez y de fiabilidad.la validez del constructo presentó una solución bifactorial según el método de rotación Varimax. Además, hubo una consistencia interna total alta para el cuestionario (alfa de Cronbach de 0,977) y para los factores encontrados (de 0,966 y 0,952, respectivamente).la versión en portugués cuenta con buenas características psicométricas y, por lo tanto, es adecuada para obtener información fiable sobre la percepción de los estudiantes de enfermería sobre el tipo de supervisión proporcionada en la práctica clínica, y esta versión es adecuada para la mejora de las prácticas pedagógicas.

The presence of an isoform of glyceraldehyde-3-phosphate dehydrogenase (kmGAPDH1p) associated with the cell wall of a flocculent strain of Kluyveromyces marxianus was the first report of a non-cytosolic localization of a glycolytic enzyme, but the mechanism by which the protein is transported to the cell surface is not known. To identify structural features that could account for the multiple localizations of the protein, the three-dimensional structure of kmGAPDH1p was determined by x-ray crystallography and small angle x-ray scattering. The x-ray crystallographic structure of kmGAPDH1p revealed a dimer, although all GAPDH homologs studied thus far have a tetrameric structure with 222 symmetry. Interestingly, the structure of kmGAPDH1p in solution revealed a tetramer with a 70 degrees tilt angle between the dimers. Moreover, the separation between the centers of the dimers composing the kmGAPDH1p tetramer diminished from 34 to 30 A upon NAD(+) binding, this latter value being similar to the observed in the crystallographic models of GAPDH homologs. The less compact structure of apo-kmGAPDH1p could already be the first image of the transition intermediate between the tetramer observed in solution and the dimeric form found in the crystal structure, which we postulate to exist in vivo because of the protein's multiple subcellular localizations in this yeast species.

We describe a 29-year-old pregnant woman at 16 weeks gestation and antiphospholipid antibodies who developed nephrotic syndrome with massive hematuria. Renal biopsy evidenced chronic glomerular lesions of ischemic nature without proliferative changes and immune deposits suggestive of lupus nephritis. Anticoagulation was initiated, along supportive measures, and the patient recovered completely. This case demonstrates that chronic renal lesions of antiphospholipid syndrome may present with marked clinical manifestation including hypertension, massive proteinuria and hematuria, resembling the course of acute thrombotic microangiopathy and/or lupus nephritis.

OBJECTIVE: To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification. METHODS: Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54 ± 9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman's correlation coefficients. RESULTS: The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis. CONCLUSIONS: Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.

Summary Hepatic fibrosis staging is based on semiquantitative scores. Digital imaging analysis (DIA) appears more accurate because fibrosis is quantified in a continuous scale. However, high cost, lack of standardization and worldwide unavailability restrict its use in clinical practice. We developed an inexpensive and widely available DIA technique for fibrosis quantification in hepatitis C, and here, we evaluate its reproducibility and correlation with semiquantitative scores, and determine the fibrosis percentage associated with septal fibrosis and cirrhosis. 282 needle biopsies staged by Ishak and METAVIR scores were included. Images of trichrome-stained sections were captured and processed using Adobe® Photoshop® CS3 and Adobe® Bridge® softwares. The percentage of fibrosis (fibrosis index) was determined by the ratio between the fibrosis area and the total sample area, expressed in pixels calculated in an automated way. An excellent correlation between DIA fibrosis index and Ishak and METAVIR scores was observed (Spearman's r = 0.95 and 0.92; P

Injury or bulging subepithelial mucosal lesions are covered with normal mucosa, usually asymptomatic. Most are diagnosed in radiology or endoscopy, which may correspond to any layer of the body wall (intramural) or non-belonging to the wall (extramural). This article describes studies for analysis of endoscopic ultrasonography (EUS) as a diagnostic method with high accuracy on the finding of subepithelial lesion. The authors review the literature on the endoscopic ultrasound features of subepithelial lesions and differentiation in intra-or extramural, source layer, echogenicity, vascularity, size and margins, fine needle aspiration (FNA) and needle biopsies of type "trucut" for histological analysis. The EUS has the best combination of accuracy in the diagnosis of gastrointestinal wall layer compromised by lesions or masses, besides studying the echogenicity of the lesion, which helps in differential diagnosis. EUS is safe and detailed, considered the best imaging for definitive diagnosis and therapeutic planning of subepithelial lesions.

Infliximab is an effective agent in the treatment of patients with Crohn’s disease. Therapy with infliximab is generally well tolerated but there are concerns about its effects on the incidence of cancer. This case report refers to a 47-year-old patient with long-standing Crohn’s disease, without a family history of colorectal cancer, who had a previous diagnosis of low-grade dysplasia that was not confirmed in subsequent studies, and was diagnosed with adenocarcinoma of the colon with peritoneal invasion after the fourth infusion of infliximab.

Maternal vascular anomalies, potentially severe for the fetus, can jeopardize uterine perfusion, which demands more caution by the anesthesiology team. The objective of this report was to demonstrate the anesthetic conduct for a cesarean section on a pregnant woman with hipoplasia of the distal aorta, just below the renal arteries, with stenosis of the renal artery and absence of the iliac arteries.This is a 30-year old patient, weighing 54 kg, on her second pregnancy, with a history of an uncomplicated cesarean section. During the gestational echocardiography on the 12th week, it was observed an interruption of the distal aorta, just below the renal arteries. The patient was referred for coronary angiography, which demonstrated hypoplasia of the distal aorta, just below the renal arteries, and absence of the iliac arteries. During the clinical investigation, the patient remained asymptomatic, except for hypertension and claudication during great efforts. She underwent continuous epidural anesthesia and the dose of the anesthetic was titrated as needed for the cesarean section. Initially, 50 mg of 0.5% bupivacaine without vasoconstrictor and 10 microg of sufentanil were administered. After 15 minutes, anesthesia was complemented with 25 mg of 0.5% bupivacaine, which was enough to achieve an adequate level of blockade. The cesarean section was performed without intercurrences, and the fetus was born in good clinical conditions.The use of continuous epidural block in fractionated doses demonstrated to be a safe anesthetic technique for this procedure because it reduces the risks of maternal hypotension, inherent to the spinal block, and also minimized the placentary transference of drugs, which is the case with general anesthesia. Titration of drugs through the epidural catheter allowed reaching an adequate anesthetic level for this type of surgery.

Difficult airways require fast action by the anesthesiologist often requiring complementary devices to ensure patent airways. However, several of those devices are expensive and require training in order to be used. The bougie, a simple and disposable device can also be manufactured by the anesthesiologist, making it a low cost tool.Bougies are composed of one introducer that when inserted in the trachea helps orienting the introduction of the tracheal tube. It is a simple tool, easy to use, low in cost, and has been shown to be very useful in unexpected difficult airways.The bougie has shown to be a valuable tool in the armamentarium of the anesthesiologist, and it is indicated in a wide range of situations.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid beta-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T(4) and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1-14) and (15-42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an alphaAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted alphaAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology.

Objective To evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients. Methods Fifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test. Results Steatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening. O câncer colorretal (CCR) é a terceira neoplasia mais freqüente no mundo. A mortalidade persiste inalterada nos últimos 50 anos a despeito dos avanços obtidos em diagnóstico e tratamento. Significativa parcela dos doentes se apresenta com tumores em estágio avançado ou incuráveis de onde se depreende a necessidade de rastreamento dos pacientes com lesões pré-malignas (pólipos adenomatosos) como resultado de herança genética ou idade, e de vigilância dos portadores de doença inflamatória intestinal de longa evolução. Na medida em que existem diferentes grupos de risco identificáveis para CCR e diferentes estratégias para o rastreamento, há que se determinar o protocolo de triagem capaz de oferecer maior relação custo-benefício. Uma vez que o objetivo das técnicas de rastreamento é diminuir a morbi-mortalidade da população analisada, o presente trabalho objetiva conhecer, sob essa perspectiva, os resultados dos estudos disponíveis até o momento para o rastreamento do CCR. Os principais métodos de rastreamento incluem, isoladamente ou em associação, o emprego da pesquisa de sangue oculto nas fezes, a sigmoidoscopia e o exame colonoscópico. As evidências de literatura a respeito dos métodos de rastreamento para os diversos grupos de risco específicos são insuficientes e, freqüentemente, não envolvem estudos controlados. A necessidade de realização desses estudos associada ao progresso nos estudos de genética molecular resultará em maior eficácia e menor custo associados ao rastreamento do CCR.

OBJECTIVE To describe the application of positive deviance as a strategy to prevent and control bloodstream infections. METHOD An intervention study with nursing and medical team members working in an intensive care unit in a university hospital, between June and December 2014. The four steps of the positive defiance methodology were applied: to define, to determine, to discover and to design. RESULTS In 90 days, 188 actions were observed, of these, 36.70% (n=69) were related to catheter dressing. In 81.15% (n=56) of these dressings, the professionals most adhered to the use of flexible sterile cotton-tipped swabs to perform antisepsis at catheter entry sites and fixation dressing. CONCLUSION Positive deviance contributed to the implementation of proposals to improve work processes and team development related to problems identified in central venous catheter care. Resumen OBJETIVO Describir la aplicación del Positive Deviance como estrategia en la prevención y control de la infección de corriente sanguínea. MÉTODO Estudio de intervención realizado en la Unidad de Cuidados Intensivos de un hospital universitario, con los miembros de los equipos de enfermería y médico, de junio a diciembre de 2014. Fueron aplicados los cuatro pasos de la metodología Positive Deviance: Definir, Determinar, Descubrir y Dibujar. RESULTADOS En 90 días 188 acciones fueron observadas; de estas, 36,70% (n=69) estaban relacionadas con los apósitos de los catéteres. En el 81,15% (n=56) de esos apósitos, el empleo del bastoncillo estéril para la realización de la antisepsia del sitio de inserción del catéter y de su placa de fijación fue la acción de mayor adhesión. CONCLUSIÓN El Positive Deviance ayudó la implantación de propuestas de mejorías de proceso laboral y el desarrollo del equipo para los problemas identificados en el cuidado con el catéter venoso central. Resumo OBJETIVO Descrever a aplicação do Positive Deviance como estratégia na prevenção e no controle da infecção de corrente sanguínea. MÉTODO Estudo de intervenção realizado na Unidade de Terapia Intensiva de um hospital universitário, com os membros das equipes de enfermagem e médica, de junho a dezembro de 2014. Foram aplicados os quatro passos da metodologia Positive Deviance: Definir, Determinar, Descobrir e Desenhar. RESULTADOS Em 90 dias 188 ações foram observadas, destas, 36,70% (n=69) estavam relacionadas aos curativos dos cateteres. Em 81,15% (n=56) desses curativos, o uso da haste flexível estéril para realização da antissepsia do local de inserção do cateter e de sua placa de fixação foi a ação de maior adesão CONCLUSÃO O Positive Deviance auxiliou na implementação de propostas de melhorias de processo de trabalho e no desenvolvimento da equipe para os problemas identificados no cuidado com o cateter venoso central.