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ABSTRACT: Over the past decade, the Agency for Healthcare Research and Quality and The Joint Commission have identified that communication problems are a root cause of most serious adverse events and that patients with limited English proficiency are more likely than others to suffer physical harm when such errors occur. It is essential to educate nursing students on the challenges of patients with limited English proficiency and empower them with tools, such as the National Culturally and Linguistically Appropriate Services standards, to minimize this phenomenon in their future nursing practice. We describe an educational intervention designed to accomplish this using Kolb's experiential learning theory as a foundation for implementation.
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Aprendizagem Baseada em Problemas , Estudantes de Enfermagem , HumanosRESUMO
There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.
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Antígenos CD34/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco de Sangue Periférico/metabolismo , Adolescente , Adulto , Doadores de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Adulto JovemRESUMO
BACKGROUND: Recently, novel protocol utilizing Continuous Mononuclear Cell Collection (cMNC) have been introduced for leukapheresis. We compared the efficacy of cMNC with an older protocol - mononuclear cell collection (MNC) for CD34+ cell collection in unrelated donors with negative stem cell collection predictors. MATERIAL AND METHODS: Retrospective data from a series of 258 consecutive unrelated hematopoietic stem cell donors was included in this single-center study (80 donors collected with cMNC and 178 with MNC). The donors with poor predictors for collection such as low number of circulating CD34+ cells and/or weight disproportion were assigned to the cMNC arm. RESULTS: The cMNC protocol yielded a higher number of CD34â¯+â¯cells per donor body weight (7.63â¯×â¯106/kg vs 6.82â¯×â¯106/kg, pâ¯=â¯0.027). One apheresis was sufficient for collection of target cell number in 89% individuals from both groups despite negative predictors in the cMNC group. In donors with CD34â¯+â¯cell count <100/µL and a body weight disproportion between donor and recipient one apheresis was sufficient in 83% of donors in cMNC group and in 58% in MNC group (pâ¯=â¯0.0345) with collection efficiency CE2% values of 61% for cMNC and 62% for MNC (pâ¯=â¯0.77). CONCLUSION: cMNC protocol is more efficient in donors with low pre-apheresis CD34+ cell count and weight disproportion between donor and recipient. This suggests that the use of cMNC in unrelated donors could possibly further improve the results of HSC collections.
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Remoção de Componentes Sanguíneos/métodos , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucócitos Mononucleares/metabolismo , Transplante Homólogo/métodos , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. RESULTS AND CONCLUSIONS: The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2 ) and cyclophosphamide (> 2 g/m2 ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.
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Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Antígenos CD34/análise , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Polônia , Diálise Renal , Estudos Retrospectivos , Transplante AutólogoRESUMO
We report on the determination of the spore concentration and the species composition of the airborne fungi in selected caves of the Tatra Mountains, Poland. The following caves were surveyed: Mylna, Oblazkowa, Mrozna, Zimna and Naciekowa. The sampling was carried out in July 2015 and in January 2016. The aeromycological analyses were performed with the impact method, using the Air Ideal 3P apparatus and potato dextrose agar (PDA, Biocorp) culture medium. In the course of the July 2015 analysis, 17 species of fungi were isolated and 11 species were isolated in January 2016. In Mylna and Naciekowa caves, the dominant species were Cladosporium cladosporioides and Stachybotrys cylindrospora. In Oblazkowa cave, Rhizoctonia predominated and in Zimna cave-the colonies of the yeast-like fungi, along with S. cylindrospora. In Mrozna cave, Penicillium notatum was the most abundant taxon. In the winter time, in the majority of the caves Penicillium spp. predominated, with the exception of Mrozna and Naciekowa caves where Aspergillus niger was dominant. We propose that aeromycological monitoring be performed regularly in the following caves: Mrozna, Naciekowa and Zimna.
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The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.
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Medicamentos Biossimilares/administração & dosagem , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Doadores de Tecidos , Adulto , Feminino , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagemRESUMO
Health disparities, especially among minorities, persist; obesity is a national concern; and the combined effect can be significant for families and populations. In an effort to address obesity at an early age, the National Association of Hispanic Nurses (NAHN), developed the Muevete USA™ project. Muevete USA™ (from the Spanish verb for "to move") features five lesson plans on healthy lifestyles for children and their families. This article describes Muevete USA™, the partnership with a local school of nursing, the implementation of the program at the local level and the emerging program and student outcomes of a successful partnership.
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Pesquisa Participativa Baseada na Comunidade , Estudantes de Enfermagem , Criança , Saúde da Criança , Humanos , Obesidade , Instituições AcadêmicasRESUMO
The addition of rituximab to standard chemotherapy has improved the results of the treatment of B cell non-Hodgkin's lymphomas. Under specific circumstances, it can be administered locally, as an alternative to systemic administration. We administered rituximab intrapericardially in an attempt to control pericardial effusion. We report the case of an 85-year-old woman, diagnosed with marginal zone lymphoma, who developed heart failure due to lymphomatous infiltration of the pericardium. We discuss in detail the possibility of intrapericardial treatment of such patients. The patient received rituximab intrapericardially at a dose of 100 mg in addition to systemic rituximab, cyclophosphamide, vincristine and prednisone immunochemotherapy. The treatment proved to be safe and effective. The patient has remained in good health for more than 3 years at the time of writing. Intrapericardial administration of rituximab may be a valuable therapeutic option for patients with lymphoma that involves the pericardium and heart.
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Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Cardíacas/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Derrame Pericárdico/tratamento farmacológico , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Feminino , Neoplasias Cardíacas/patologia , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Invasividade Neoplásica , Derrame Pericárdico/patologia , Prednisona/administração & dosagem , Indução de Remissão , Rituximab , Vincristina/administração & dosagemRESUMO
Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.
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Social media is one of the most common sources of medical information. We aimed to evaluate the information contained on websites, including social media and descriptions of fundraisers, in terms of the reliability of knowledge about SMA and gene therapy with onasemnogen abeparvovec. We used a set of available online links found using the Newspointtool. Initially, 1525 texts were included in the study, and after applying the inclusion and exclusion criteria, 112 texts were qualified for analysis using the DISCERN scale and the set of questions prepared by the authors. We observed that most of the texts had poor (48.65%) and medium (27.03%) reliability in the final reliability assessment. All the texts selected for the study were related to gene therapy, although few contained key information about it. In addition, the authors of the entries used various words and phrases that influenced the readers' perceptions of the text. Of the analyzed sources, 68.8% had an emotional component. Social media is a poor source of information about gene therapy for SMA in Poland. The analyzed texts do not provide a full and complete description of the SMA problem. However, it is important to remember that the Internet is a changing source of information and will hopefully contain more relevant entries in the future.
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To elucidate the mechanisms of glomerulonephritis, including Goodpasture's syndrome, mouse models are used that use heterologous Abs against the glomerular basement membrane (GBM) with or without preimmunization with foreign IgG from the same species. These studies have revealed the requirement of either FcgammaR or complement, depending on the experimental model used. In this study, we provide evidence that both FcgammaR and complement are obligatory for a full-blown inflammation in a novel attenuated passive model of anti-GBM disease. We demonstrate that administration of subnephritogenic doses of rabbit anti-GBM Abs followed by a fixed dose of mouse mAbs to rabbit IgG, allowing timing and dosing for the induction of glomerulonephritis, resulted in reproducible complement activation via the classical pathway of complement and albuminuria in wild-type mice. Because albuminuria was absent in FcR-gamma-chain(-/-) mice and reduced in C3(-/-) mice, a role for both FcgammaR and complement is postulated. Because C1q(-/-) and C4(-/-) mice lacking a functional classical and lectin pathway did develop albuminuria, we suggest involvement of the alternative pathway of complement. Anti-GBM glomerulonephritis occurs acutely following the administration of mouse anti-rabbit IgG, and proceeds in a chronic fashion dependent on both FcgammaR and complement. This novel attenuated model allows elucidating the relative contribution of different mediator systems of the immune system to the development of renal injury, and also provides a platform for the assessment of different treatment protocols and evaluation of drugs that ultimately may be beneficial for the treatment of anti-GBM mediated glomerulonephritides.
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Doença Antimembrana Basal Glomerular/imunologia , Nefrite/imunologia , Receptores de Complemento/fisiologia , Receptores de IgG/fisiologia , Albuminúria/etiologia , Animais , Doença Antimembrana Basal Glomerular/etiologia , Doença Antimembrana Basal Glomerular/patologia , Autoanticorpos , Ativação do Complemento , Imunoglobulina G/administração & dosagem , Inflamação , Camundongos , Nefrite/patologiaRESUMO
BACKGROUND: Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC) > 2 mg/dL or estimated glomerular filtration rate (eGFR) < 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria. PATIENTS AND METHODS: We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR < 60 mL/min, treated with ASCT from 1998 to 2004. RESULTS: The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P < .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC > 1.4 mg/dL and eGFR < 55mL/min. CONCLUSIONS: We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.
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Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Adulto , Idoso , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Insuficiência Renal/classificação , Transplante AutólogoRESUMO
Angiogenesis represents one of the critical mechanisms that facilitates carcinoma development. The study objective was to evaluate whether the microsatellite instability of colorectal carcinoma has impact on the angiogenesis activity in liver metastases.In a cohort of 80 randomly selected patients with stage IV colorectal carcinoma, 30% were recognized as microsatellite unstable (Microsatellite instability high-frequency (MSI-H)). The endothelial progenitor cell fraction (CD309+) was counted within the subpopulation of CD34+CD45+ cell and CD34+CD45- cells by flow cytometer. vascular endothelial growth factor (VEGF) factor levels were quantified in serum samples by enzyme-linked immunosorbent assay (ELISA). A control group consisted of 36 healthy volunteers. The relationship of genomic instability to angiogenesis activity was evaluated by multivariate analysis in comparison to the controls, adopting a Pâ<â.05 value as statistically significant.The expression of endothelial progenitor cells (EPCs) and VEGF was significantly higher in MSI-H compared to both microsatellite stability (MSS) patients and healthy controls (Pâ<â.008). Multi-parametric analysis showed microsatellite instability (OR=9.12, Pâ<â.01), metastases in both lobes (ORâ=â32.83, Pâ<â.001) and simultaneous metastases outside liver (ORâ=â8.32, Pâ<â.01), as independent factors associated with increased angiogenesis as assessed by measures of EPC and VEGF. A higher percentage of EPCs within the white blood cell fraction (total % EPCs / white blood cells (WBC)) and higher serum concentrations of VEGF were present in patients with MSI-H colorectal cancer, and not with MSS cancers (Pâ<â.001).MSI-H patients with colorectal cancer metastases are associated with the overexpression of circulating EPCs and VEGF, potentially driving angiogenesis. This should be considered in therapeutic decision-making.
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Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Instabilidade de Microssatélites , Neovascularização Patológica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Células Progenitoras Endoteliais/metabolismo , Feminino , Instabilidade Genômica/genética , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Telemedicina/métodos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismoAssuntos
Leucemia Prolinfocítica de Células T , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia Prolinfocítica de Células T/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios XRESUMO
The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level >/=0.1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0.0001), as well as in the standard risk (SR, P = 0.0003) and high-risk (P = 0.008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0.1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0.001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.
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Antígenos CD/análise , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células da Medula Óssea/imunologia , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/imunologia , Polônia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Risco , Adulto JovemRESUMO
Background: The International Classification of Functioning, Disability, and Health (ICF) Core Sets for children and youth with cerebral palsy (CP) offer service providers and stakeholders a specific framework to explore functioning and disability for assessment, treatment, evaluation, and policy purposes in a global context. Objective: Describe global initiatives applying the ICF Core Sets for children and youth with CP, with a focus on contributions to clinical practice and challenges in their implementation. Methods: This is a descriptive cross-sectional study. Ongoing initiatives applying the ICF Core Sets for CP in Russia, Poland, Malawi, and Brazil are included. Results: The main contributions of applying the ICF Core Sets for children and youth with CP include: (1) an objective description of abilities and limitations in everyday activities; (2) a consistent identification of facilitators and barriers influencing functioning; (3) a practical communication tool promoting client-centered care and multidisciplinary teamwork; and, (4) a useful guideline for measurement selection. The main challenges of adopting the ICF Core Sets are related to lack of ICF knowledge requiring intense training and translating results from standardized measures into the ICF qualifiers in a consistent way. Conclusions: Global initiatives include research and clinical applications at the program, service and system levels. The ICF Core Sets for CP are useful tools to guide service provision and build profiles of functioning and disability. Global interprofessional collaboration, capacity training, and informatics (e-records) will maximize their applications and accelerate adoption.
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Paralisia Cerebral/classificação , Avaliação da Deficiência , Pessoas com Deficiência/classificação , Atividades Cotidianas , Adolescente , Brasil , Criança , Humanos , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Malaui , Polônia , Federação RussaRESUMO
Pathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, inflammatory diseases, atherosclerosis, and cancer. Studies of oxidative stress are however complicated by the low concentration of oxidation products. To resolve this problem, we tested a new derivative of aminoadipic semialdehyde (Fmoc-Aea-OH) in the solid-phase synthesis of carbonylated peptides. We prepared a series of peptides with free and acetylated N-terminal amino groups using the Fmoc-Aea-OH reagent. LC-MS, ESI-MS, and MS/MS spectra confirmed the sequences of the modified peptides, although the LC-MS and ESI-MS spectra were dominated by signals corresponding to dehydration products. NMR studies of acetylated products revealed that the dominant product formed in this reaction contains a 1,2,3,4-tetrahydropyridine-2-carboxylic acid residue. Another side reaction in this system was the cleavage of the amide bond between the Aea residue and the amino acid moiety preceding it resulting in the formation of a side product with a six-membered ring at the N-terminus (2,3,4,5-tetrahydropyridine-2-carboxylic acid residue). We found that, depending on the peptide sequence, one of those side products is predominant. Our work suggests new methods for the solid-state synthesis of peptides containing unnatural amino acids.
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Adipatos/química , Aldeídos/química , Estresse Oxidativo , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Cromatografia Líquida , Ciclização , Oxirredução , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Schools of nursing have moved to multiple choice test questions to help prepare students for licensure and practice. However, students can buy test banks to help them "get through" nursing school. Accurate assessment of nursing students' knowledge and judgment comprises access to test banks. METHOD: The purpose of this exploratory study was to gain an understanding about nursing faculty's knowledge concerning test bank security issues, to assess whether publishers were aware of this issue, and vendor's reasons for supplying test banks to students. RESULTS: Overall, the results indicated that the majority of faculty were unaware of student access to test banks, and although most do not use test banks verbatim, general consensus existed that test bank security is a concern. CONCLUSION: Implications include increasing faculty awareness of test bank access by students, supporting educators to develop their own test bank items, and promoting security of all examinations. [J Nurs Educ. 2017;56(5):292-294.].
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Bases de Dados como Assunto , Educação em Enfermagem , Avaliação Educacional , Atitude do Pessoal de Saúde , Comércio , Docentes de Enfermagem , Humanos , Internet , Inquéritos e QuestionáriosRESUMO
Mannan-binding lectin (MBL) is a major initiator of the lectin pathway (LP) of complement. Polymorphisms in exon 1 of the MBL gene are associated with impaired MBL function and infections. Functional assays to assess the activity of the classical pathway (CP) and the alternative pathway (AP) of complement in serum are broadly used in patient diagnostics. We have now developed a functional LP assay that enables the specific quantification of autologous MBL-dependent complement activation in human serum. Complement activation was assessed by ELISA using coated mannan to assess the LP and coated IgM to assess the CP. Normal human serum (NHS) contains IgG, IgA and IgM antibodies against mannan, as shown by ELISA. These antibodies are likely to induce CP activation. Using C1q-blocking and MBL-blocking mAb, it was confirmed that both the LP and the CP contribute to complement activation by mannan. In order to quantify LP activity without interference of the CP, LP activity was measured in serum in the presence of C1q-blocking Ab. Activation of serum on coated IgM via the CP resulted in a dose-dependent deposition of C1q, C4, C3, and C5b-9. This activation and subsequent complement deposition was completely inhibited by the C1q-blocking mAb 2204 and by polyclonal Fab anti-C1q Ab. Evaluation of the LP in the presence of mAb 2204 showed a strong dose-dependent deposition of C4, C3, and C5b-9 using serum from MBL-wildtype (AA) but not MBL-mutant donors (AB or BB genotype), indicating that complement activation under these conditions is MBL-dependent and C1q-independent. Donors with different MBL genotypes were identified using a newly developed oligonucleotide ligation assay (OLA) for detection of MBL exon 1 polymorphisms. We describe a novel functional assay that enables quantification of autologous complement activation via the LP in full human serum up to the formation of the membrane attack complex. This assay offers novel possibilities for patient diagnostics as well as for the study of disease association with the LP.
Assuntos
Via Alternativa do Complemento , Proteínas do Sistema Complemento/fisiologia , Lectina de Ligação a Manose/fisiologia , Anticorpos/sangue , Anticorpos/imunologia , Complemento C1q/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/fisiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Mananas/imunologia , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Lectina de Ligação a Manose/genética , MutaçãoRESUMO
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90% of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke(1). Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers' instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p = 0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p = 0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r = -0.54, p = 0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p = 0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for MS activity.