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PURPOSE: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. METHODS: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. RESULTS: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. CONCLUSION: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.
Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Adulto , Pessoa de Meia-Idade , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Brasil/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genéticaRESUMO
BACKGROUND: Diabetes Mellitus (DM) is considered a chronic disease with numerous secondary complications that negatively affect the quality of life of patients. However, the specific, known and validated instruments for Brazilian Portuguese are too extensive, which often makes their use infeasible. OBJECTIVE: To validate the internal structure of the Brazilian version of the Diabetes Quality of Life (DQOL) measure. METHODOLOGY: Patients with DM type 1 or 2, between the ages of 18 and 76, were evaluated between April 2022 and May 2022. The survey was conducted online using the Google Forms platform. The original DQOL contains 46 multiple-choice questions organized into four domains. For structural validity, confirmatory factor analysis (CFA) was performed using RStudio software (Boston, MA, USA) with the packages lavaan and semPlot. RESULTS: A total of 354 subjects were evaluated. The 3-domain, 24-item version of the DQOL was the most adequate, with acceptable values for all fit indices (chi-square/GL < 3, TLI and CFI > 0.90, and RMSEA and SRMR < 0.08). CONCLUSION: The structure with three domains and 24 items is the most appropriate based on factor analysis. The Brazilian version of the DQOL with a structure of 3 domains and 24 items has adequate measurement properties that support its use in the clinical and scientific context in patients with DM.
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Diabetes Mellitus Tipo 1 , Qualidade de Vida , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Brasil , Inquéritos e Questionários , Idioma , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Hope is an important resource that helps patients and families thrive during difficult times. Although several studies have highlighted the importance of hope in different contexts, its specific manifestations in the realm of advanced chronic illness need further exploration. In this study, we sought to elucidate the intricate interplay between the construct of hope and the lived experience of advanced chronic illness within patient-caregiver dyads. Our objectives were (a) to explore the dyadic experience of hope as a changing dynamic over time for patients living with advanced chronic illness and their informal caregivers and (b) to evaluate variations of hope and symptom burden across time. METHODS: We conducted a longitudinal mixed-methods study with a convergent design between December 2020 and April 2021. Patients living with advanced chronic illness and informal caregivers participated as a dyad (n = 8). The Herth Hope Index scale was used to measure dyads' level of hope and the Edmonton Symptom Assessment System was used to measure patients' symptom burden. Descriptive statistics were undertaken. A thematic analysis as described by Braun and Clarke was conducted to analyze dyadic interview data. Dyads' experience of hope was described by using the six dimensions of hope in the Model of Hope of Dufault and Martocchio. RESULTS: Dyadic scores of hope and patients' symptom burden were stable over time. The constructs of hope in dyads included "Living one day at the time," "Having inner force/strength," and "Maintaining good health." Changes in patterns of hope were captured for each dyad in their transition over time. Data converged for all dyads except one. CONCLUSIONS: The findings of our study show a constant presence of hope even in the face of adversity. Healthcare professionals must find ways to promote hope in dyads of patients living with advanced chronic diseases. Nurses play a pivotal role; dyadic interviews should be promoted to create a safe space for both patients and informal caregivers in order to share experiences. More research is needed to address patients' and informal caregivers' hope in chronic illness because current hope-based interventions primarily target cancer diagnoses.
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Cuidadores , Esperança , Humanos , Estudos Longitudinais , Masculino , Feminino , Doença Crônica/psicologia , Portugal , Pessoa de Meia-Idade , Idoso , Cuidadores/psicologia , Pesquisa Qualitativa , Idoso de 80 Anos ou mais , Adulto , Adaptação PsicológicaRESUMO
BACKGROUND: Leishmania (Viannia) braziliensis Thor strain exhibits a heterogeneous composition comprised of subpopulations with varying levels of infectivity. Clonal subpopulations were previously obtained from the strain Thor by sorting single-parasites and proceeding cultivation. The subpopulations used in this study are named Thor03, Thor 10 and Thor22. OBJECTIVES: Phenotypic characteristics of the parasite, specially focusing on virulence factors and resistance to the antimicrobial mechanisms of macrophages, were investigate in these subpopulations. METHODS: Cellular and molecular biology, as well as biochemistry approaches were applied to obtain the data analysed in this study. FINDINGS: Relative quantification of gene expression was measured for calpain, cysteine protease B (CPB), and subtilisin proteases but no significant differences in these genes' expression among subpopulations was observed. However, subtilisin and CPB proteins were assessed as more abundant in Thor03 by fluorescence-labelled flow cytometry technique. Western Blotting assays, as semi-quantitative analysis in gel, showed higher concentrations of subtilisin (110 to 50 kDa) and CPB (40 to 18 kDa) in extract of intracellular amastigotes from subpopulations Thor03 and Thor10 and calpain (60 to 25 kDa) showed no significant differences among subpopulations. Complementary, higher trypanothione reductase activity was observed in Thor10 intracellular amastigotes and assays of susceptibility to hydrogen peroxide-inducing agents and nitric oxide donors conducted with promastigotes revealed greater resistance to in vitro oxidative stress induction for Thor10, followed by Thor03. MAIN CONCLUSIONS: The data obtained for the virulence factors explored here suggest how multiple coexisting phenotypic-distinct subpopulations may contribute in adaptability of a single L. (V.) braziliensis strain during infection in the host cells.
Assuntos
Leishmania braziliensis , Leishmania braziliensis/enzimologia , Leishmania braziliensis/genética , Leishmania braziliensis/efeitos dos fármacos , Animais , Macrófagos/parasitologia , Western Blotting , Citometria de Fluxo , Fatores de Virulência , Peptídeo Hidrolases/metabolismo , Fenótipo , NADH NADPH OxirredutasesRESUMO
To explore severity and progression biomarkers, we examined the clinical relevance of multiple cytokines and mediators involved in the inflammatory response in periodontitis. A cohort of 68 patients was enrolled in the study and periodontal status assessed by the current classification of periodontal diseases. Immune mediators present in saliva, of both patients and healthy controls, were quantified using a Legendplex-13 panel. Clinic parameters were significantly higher in PD patients compared with HC, with a strong significant association with the disease severity (stage) (p < 0.001), but not with progression (grade). The panel of immune mediators evidenced elevated levels of pro-inflammatory cytokines IL-6 and IL-1ß as disease established (p < 0.01). IL-1ß/IL-1RA ratio was increased in PD patients, being associated with disease stage. An anti-inflammatory response was spotted by higher IL-10. Lower levels of IL-23 and IP-10 were associated with disease severity. No significant statistical differences were found by grade classification. Moreover, salivary IL-1ß and IL-6 exhibited significant positive correlations with several clinical measurements (PI, BOP, PPD, CAL), while IP-10 showed a statistical negative correlation with BOP, PPD, and CAL. These insights highlight the complexity of the periodontitis inflammatory network and the potential of cytokines as biomarkers for refined diagnostic and therapeutic strategies.
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Biomarcadores , Interleucina-10 , Interleucina-1beta , Interleucina-6 , Periodontite , Saliva , Índice de Gravidade de Doença , Humanos , Biomarcadores/metabolismo , Feminino , Masculino , Saliva/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/análise , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Interleucina-10/metabolismo , Periodontite/metabolismo , Periodontite/patologia , Periodontite/imunologia , Adulto , Estudos de Casos e ControlesRESUMO
Thiazolidinediones (TZD) are synthetic molecules that have a range of biological effects, including antifibrotic and anti-inflammatory, and they may represent a promising therapeutic strategy for systemic sclerosis (SSc). The aim of this study was to investigate the immunomodulatory and antifibrotic properties of LPSF/GQ-16, a TZD derivative, in peripheral blood mononuclear cells (PBMC) from SSc patients and in a murine model of SSc HOCl-induced. The PBMC of 20 SSc patients were stimulated with phytohemagglutinin (PHA) and treated with LPSF/GQ-16 for 48 h, later cytokines in the culture supernatants were quantified by sandwich enzyme-linked immunosorbent assay (ELISA) or cytometric bead array (CBA). Experimental SSc was induced by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. HOCl-induced SSc mice received daily treatment with LPSF/GQ-16 (30 mg/kg) through intraperitoneal injections during the same period. Immunological parameters were evaluated by flow cytometry and ELISA, and dermal and pulmonary fibrosis were evaluated by RT-qPCR, hydroxyproline dosage and histopathological analysis. In PBMC cultures, it was possible to observe that LPSF/GQ-16 modulated the secretion of cytokines IL-2 (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.001), IL-17A (p = 0.006), TNF (p < 0.001) and IFN-γ (p < 0.001). In addition, treatment with LPSF/GQ-16 in HOCl-induced SSc mice promoted a significant reduction in dermal thickening (p < 0.001), in the accumulation of collagen in the skin (p < 0.001), down-regulated the expression of fibrosis markers in the skin (Col1a1, α-Sma and Tgfß1, p < 0.001 for all) and lungs (Il4 and Il13, p < 0.001 for both), as well as reduced activation of CD4 + T cells (p < 0.001), B cells (p < 0.001) and M2 macrophages (p < 0.001). In conclusion, LPSF/GQ-16 showed immunomodulatory and antifibrotic properties, demonstrating the therapeutic potential of this molecule for SSc.
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Fibrose Pulmonar , Escleroderma Sistêmico , Tiazolidinedionas , Humanos , Animais , Camundongos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Leucócitos Mononucleares , Ácido Hipocloroso , PPAR gama , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/tratamento farmacológico , CitocinasRESUMO
AIMS: KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) ß2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL-286 in male healthy volunteers to establish dosing to be used in the SCI patient population. METHODS: The design was a double blind, randomized, placebo-controlled dose escalation study in 2 parts: a single ascending dose adaptive design with a food interaction arm, and a multiple ascending dose design. RARß2 mRNA expression was evaluated in white blood cells. RESULTS: At the highest single and multiple ascending doses (100 mg), no trends or clinically important differences were noted in the incidence or intensity of adverse events (AEs), serious AEs or other safety assessments with none leading to withdrawal from the study. The AEs were dry skin, rash, skin exfoliation, raised liver enzymes and eye disorders. There was an increase in mean maximum observed concentration and area under the plasma concentration-time curve up to 24 h showing a trend to subproportionality with dose. RARß2 was upregulated by the investigational medicinal product in white blood cells. CONCLUSION: KCL-286 was well tolerated by healthy human participants following doses that exceeded potentially clinically relevant plasma exposures based on preclinical in vivo models. Target engagement shows the drug candidate activates its receptor. These findings support further development of KCL-286 as a novel oral treatment for SCI.
Assuntos
Drogas em Investigação , Receptores do Ácido Retinoico , Humanos , Masculino , Voluntários Saudáveis , Relação Dose-Resposta a Droga , Área Sob a Curva , Método Duplo-CegoRESUMO
OBJECTIVE: To create, develop, and validate a scale that identifies the environmental and personal barriers that make it difficult to adhere to the practice of physical exercise on a regular basis in a population of Brazilian adults. METHODS: We include adult individuals, aged 18-59 years, practitioners or former practitioners of physical exercise, with Brazilian Portuguese as their mother tongue. In the development and validation phases of the process, 6 specialists in the field of the health assessed the content validity: firstly, the specialists were asked to freely list the questions they would ask to investigate the barriers to adherence to regulating physical activity. Secondly, after compiling all the suggestions listed and eliminating suggestions with similar content, the items suggested in the first round were sent to the specialists so that an evaluation of all questions using a 5-point Likert scale and the content validity coefficient was calculated. We then evaluated the structural validity, construct validity, reliability, internal consistency, and ceiling and floor effects of the Regular Physical Exercise Adherence Scale (REPEAS). RESULTS: Sixteen items were proposed to measure the factors that make it difficult to adhere to the regular practice of physical exercise. The internal structure of the REPEAS initially tested was based on the theoretical proposal of creating the instrument with two domains. After the structural analysis, we used the modification indices to identify the redundant items of the instrument. Consequently, the final version of the REPEAS after factor analysis had 12 items. Thus, the structure with 2 domains and 12 items presented adequate fit indices. With regard to construct validity, the REPEAS scores were compared in two distinct groups: irregular practitioners/ex-practitioners versus regular practitioners of physical exercise, in which a significant difference could be observed between groups (p < 0.001) for both the domains. Acceptable reliability was observed for the environment and personal domains, with ICC values of 0.86 and 0.94, in the same order. For internal consistency, Cronbach's alpha value was 0.908 (environmental domain) and 0.915 (personal domain), these values being adequate for the REPEAS. CONCLUSION: The REPEAS is a scale with a valid two-dimensional internal structure, consisting of 12 items, reliable and with a valid construct, which supports its use in the clinical, epidemiological, and research contexts in Brazil.
Assuntos
Terapia por Exercício , Exercício Físico , Adulto , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Brasil , PsicometriaRESUMO
OBJECTIVE: Compare heart rate variability (HRV) indices in participants with and without myogenic temporomandibular disorder (TMD). Secondarily, we correlated HRV indices with pain and quality of life variables. METHODS: This is a comparative observational cross-sectional study. Individuals of both genders with and without a history of TMD were included. Short-term heart rate variability was assessed using a Polar V800. Central sensitization was assessed using the Central Sensitization Inventory. Pain through the numeric pain scale and the impact of oral health on quality of life using the OHIP-14 questionnaire. RESULTS: A total of 80 participants were enrolled in the study: most individuals included in both groups were young adults, women and slightly overweight. We observed a decrease in HRV in the TMD group (p < 0.01) when compared to the control group. In addition, we observed a greater impact of oral health on quality of life, central sensitization in addition to high resting pain scores (p < 0.01). We observed significant correlation between the LF index of HRV and the FAI score (r = 0.311; p = 0.05). The NPS, CSI and OHIP-14 scores did not correlate with any of the HRV indices (p > 0.05). CONCLUSION: The short-term HRV in individuals with TMD is significantly lower when compared to a control group. Furthermore, there seems to be a relationship between the severity of the dysfunction and the HRV variables. CLINICAL RELEVANCE: Using portable and low-cost devices, the HRV can be easily collected and analyzed, without the need for an arsenal of equipment such as the conventional electrocardiogram. This measure can contribute to the therapy adopted and identify individuals prone to unfavorable outcomes involving ANS modulation.
Assuntos
Qualidade de Vida , Transtornos da Articulação Temporomandibular , Feminino , Humanos , Masculino , Adulto Jovem , Estudos Transversais , Frequência Cardíaca/fisiologia , DorRESUMO
Bacterial biofilm formation in low moisture food processing (LMF) plants is related to matters of food safety, production efficiency, economic loss, and reduced consumer trust. Dry surfaces may appear dry to the naked eye, however, it is common to find a coverage of thin liquid films and microdroplets, known as microscopic surface wetness (MSW). The MSW may favor dry surface biofilm (DSB) formation. DSB formation is similar in other industries, it occurs through the processes of adhesion, production of extracellular polymeric substances, development of microcolonies and maturation, it is mediated by a quorum sensing (QS) system and is followed by dispersal, leading to disaggregation. Species that survive on dry surfaces develop tolerance to different stresses. DSB are recalcitrant and contribute to higher resistance to sanitation, becoming potential sources of contamination, related to the spoilage of processed products and foodborne disease outbreaks. In LMF industries, sanitization is performed using physical methods without the presence of water. Although alternative dry sanitizing methods can be efficiently used, additional studies are still required to develop and assess the effect of emerging technologies, and to propose possible combinations with traditional methods to enhance their effects on the sanitization process. Overall, more information about the different technologies can help to find the most appropriate method/s, contributing to the development of new sanitization protocols. Thus, this review aimed to identify the main characteristics and challenges of biofilm management in low moisture food industries, and summarizes the mechanisms of action of different dry sanitizing methods (alcohol, hot air, UV-C light, pulsed light, gaseous ozone, and cold plasma) and their effects on microbial metabolism.
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Biofilmes , Indústria de Processamento de Alimentos , Microbiologia de Alimentos , Manipulação de Alimentos/métodos , BactériasRESUMO
Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.
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COVID-19 , Meningite Meningocócica , Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Brasil/epidemiologia , Humanos , Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/epidemiologia , PandemiasRESUMO
BACKGROUND: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. METHODS: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher's test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. RESULTS: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). CONCLUSION: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Feminino , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Brasil/epidemiologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mutação , Receptores ErbB/genéticaRESUMO
Cellulose nanocrystals (CNC)-based foams are promising tissue engineering materials that may facilitate implant-tissue integration and allow localized and controlled drug delivery. Herein, hybrid CNC-based foams, which are ultralightweight (30-100 mg cm-3 ), highly porous (>95%), ominiphilic and superabsorbent (1500-3000 wt% of water and/or toluene uptake) are obtained by the in situ condensation of poly(ethylene glycol) ditriethoxysilyl (TES-PEG-TES) into a 3D network, where silsesquioxane nanoparticles (SS-NP) are the crosslinking nodes, and CNC are entrapped forming ionic interactions, in a supramolecular structure. In a new approach, using 3-mercaptopropyltrimethoxysilane, sulfhydryl groups are inserted on the SS-NP periphery and S-nitrosated to enable the functionalization of SS-NP with S-nitrosothiol groups, which can nitric oxide (NO), in a process triggered by the hydration of the foams and modulated by their supramolecular structure. CNC-SS-PEG foams exhibit elevated thermal and structural stability, compressive strength compatible with various soft human tissues, and NO release rates (1-18 pmol mg-1 min-1 ) within the range of the beneficial NO actions. Thus, the CNC-SS-PEG foams herein described represent a new platform of supramolecular hybrid materials for localized delivery of NO, with potential uses in tissue engineering and other biomedical applications.
Assuntos
Celulose , Nanopartículas , Celulose/química , Humanos , Nanopartículas/química , Óxido Nítrico , Engenharia Tecidual , Água/químicaRESUMO
BACKGROUND: The Work Role Functioning Questionnaire 2.0 (WRFQ 2.0) is an instrument that measures the difficulties perceived by workers in meeting work demands, given their physical or emotional health, but it has not yet been adapted for Brazil. Thus, this study aimed to translate, cross-culturally adapt and assess the psychometric properties of the WRFQ 2.0 into Brazilian Portuguese. METHODS: This is an observational study. Initially, translation and cross-cultural adaptation into Brazilian Portuguese was carried out. After that, this version was submitted to an evaluation of its internal structure. The internal consistency and test-retest reliability were assessed. To determine the construct validity, Spearman's correlation coefficient (rho) was used to determine the magnitude of correlation between the WRFQ 2.0 and the Work Ability Index (WAI), Numerical Pain Rating Scale (NPRS) and Self -Estimated Functional Inability because of Pain (SEFIP-work). RESULTS: The internal structure with five domains and 27 items presented adequate fit indices for the Brazilian version of the WRFQ 2.0. Adequate correlations of the five domains of the WRFQ 2.0 with the NPRS, WAI and SEFIP-work were found (rho ranged between 0.145 and 0.338). The test-retest reliability of the WRFQ 2.0 ranged from substantial to excellent (intraclass correlation coefficient ≥ 0.785) and internal consistency was adequate (Cronbach's alpha ≥ 0.852). CONCLUSION: The Brazilian Portuguese version of the WRFQ 2.0 presents valid internal structure with five domains and 27 items, adequate construct based on correlations with other instruments, and acceptable test-retest reliability and internal consistency.
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Comparação Transcultural , Idioma , Brasil , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , TraduçõesRESUMO
Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol ß-amino alcohol and ß-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three ß-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.
Assuntos
Antineoplásicos , Eugenol , Álcoois , Amino Álcoois , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Óleo de Cravo/química , HumanosRESUMO
AIM: The aim of this scoping review is to map the nurse-led care management models for patients with multimorbidity in hospital settings. BACKGROUND: Patients with multimorbidity in hospital, due their complexity, benefit a nurse-led care management model. This care management model allows for better identification of patients' needs and a person-centred approach. EVALUATION: This review followed the JBI methodology for scoping reviews. The search included the international databases Web of Science, CINAHL, MEDLINE, Nursing & Allied Health Collection and grey literature. A total of 21 articles were included in the final content analysis. KEY ISSUES: Three categories of nurse-led care management models emerged from the data, namely, nurse-led programs, case management and nurse facilitator models. The interventions focused on training, discharge support, follow-up, health promotion and patient-centred care. CONCLUSION: The centrality of the patient is a common characteristic of nurse-led care models, namely, the acquisition of disease self-management skills, preparation for hospital discharge and continuity of care in the community. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse-led care management models can empower patients to manage their chronic conditions more effectively. Adapting these care management models in hospital settings will be a challenge for nurse managers. SCOPING REVIEW PROTOCOL: The full protocol used can be accessed at doi:10.11124/jbies-20-00222.
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Multimorbidade , Papel do Profissional de Enfermagem , Hospitais , Humanos , Assistência Centrada no PacienteRESUMO
Staphylococcus saprophyticus is a primary cause of community-acquired urinary tract infections (UTIs) in young women. S. saprophyticus colonizes humans and animals but basic features of its molecular epidemiology are undetermined. We conducted a phylogenomic analysis of 321 S. saprophyticus isolates collected from human UTIs worldwide during 1997-2017 and 232 isolates from human UTIs and the pig-processing chain in a confined region during 2016-2017. We found epidemiologic and genomic evidence that the meat-production chain is a major source of S. saprophyticus causing human UTIs; human microbiota is another possible origin. Pathogenic S. saprophyticus belonged to 2 lineages with distinctive genetic features that are globally and locally disseminated. Pangenome-wide approaches identified a strong association between pathogenicity and antimicrobial resistance, phages, platelet binding proteins, and an increased recombination rate. Our study provides insight into the origin, transmission, and population structure of pathogenic S. saprophyticus and identifies putative new virulence factors.
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Infecções Comunitárias Adquiridas , Infecções Estafilocócicas , Infecções Urinárias , Animais , Humanos , Staphylococcus saprophyticus , Suínos , Fatores de VirulênciaRESUMO
Rigorous evidence reviews must follow specific guidelines designed to improve transparency, reproducibility, and to minimize biases to which traditional reviews are susceptible. While evidence synthesis methods, such as systematic reviews and maps, have been used in several research fields, the majority of reviews published in the realm of chemical engineering are nonsystematic. In this study, we incorporated principles of systematic mapping to conduct a literature review covering research on the synthesis of sugar fatty acid esters (SFAE) with Candida antarctica lipase B (CALB). Our results showed that the simple monosaccharides were the most cited sugars among studies we conducted. The direct use of renewable raw materials and frequently available resources to produce alternative sugar esters (SE) was scarcely reported in our data set. We found that free fatty acids (FFA) were the most commonly cited acyl donors amongst all publications, with lauric, oleic, and palmitic acids accounting for â¼43% of the occurrences. Tertiary alcohols (ter-butyl alcohol (T-but) and 2-methyl-2-butanol (2M2B)) and ionic liquids were the most used solvents to synthesize SE. The co-occurence analysis of keywords involving solvent terms showed that most of the papers evaluated different solvents as reaction media (mostly in the form of a bisolvent system), also investigating the impact of their choice on sugar ester productivities. Given the potential of reviews informing us of research decisions, this article reveals trends and spaces across CALB-catalyzed SE synthesis research, in addition to introducing a new methodological perspective for developing reviews in the field of chemical engineering.
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Ésteres , Proteínas Fúngicas , Lipase , Açúcares , Basidiomycota , Catálise , Esterificação , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Reprodutibilidade dos Testes , Revisões Sistemáticas como AssuntoRESUMO
Hydrogels have been used as matrices for the topical delivery of nitric oxide (NO) for achieving vasodilation, wound healing and analgesic actions. More recently, supramolecular hydrogels comprised of poly(acrylic acid) (PAA) and micellar Pluronic F127 (F127), prepared by thermal reaction, emerged as a suitable matrix for the incorporation of hydrophilic NO donors, such as S-nitrosoglutathione (GSNO). Herein, we describe an innovative method for the three-dimensional (3D) printing of cellulose nanocrystal (CNC)-containing and semi-interpenetrating PAA/F127 hydrogels by PAA photopolymerization via digital light processing (DLP), in the absence of organic solvents. Scanning electron microscopy showed that, differently from typical porous PAA-based hydrogels, the 3D printed PAA/F127/CNC hydrogels have dense morphology. By using transmission electron microscopy we confirmed for the first time the presence of F127 micelles in the printable resin, and their preservation after the photopolymerization process. The F127 micelles conferred compressive recoverability to the 3D printed PAA/F127/CNC hydrogels, widening their potential applications as soft biomaterials. PAA/F127/CNC hydrogels charged with GSNO are shown to release NO spontaneously upon hydration at initial rates that depend on the GSNO charge and are higher in the presence of CNC. As local NO release may exert cell proliferation action, 3D printed PAA/F127/CNC/GSNO hydrogels may serve as a versatile soft biomaterial for local NO delivery in regenerative medicine and other biomedical applications.
Assuntos
Hidrogéis , Nanopartículas , Resinas Acrílicas , Celulose , Óxido Nítrico , Polietilenos , Polipropilenos , Impressão TridimensionalRESUMO
OBJECTIVES: During the Middle Ages, Portugal witnessed unprecedented socioeconomic and religious changes under transitioning religious political rule. The implications of changing ruling powers for urban food systems and individual diets in medieval Portugal is poorly understood. This study aimed to elucidate the dietary impact of the Islamic and Christian conquests. MATERIALS AND METHODS: Radiocarbon dating, peptide mass fingerprinting (ZooMS) and stable isotope analysis (δ13 C, δ15 N) of animal (n = 59) and human skeletal remains (n = 205) from Muslim and Christian burials were used to characterize the diet of a large historical sample from Portugal. A Bayesian stable isotope mixing model (BSIMM) was used to estimate the contribution of marine protein to human diet. RESULTS: Early medieval (8-12th century), preconquest urban Muslim populations had mean (±1SD) values of -18.8 ± 0.4 for δ13 C 10.4 ± 1 for δ15 N, indicating a predominantly terrestrial diet, while late medieval (12-14th century) postconquest Muslim and Christian populations showed a greater reliance on marine resources with mean (±1SD) values of -17.9 ± 1.3 for δ13 C and 11.1 ± 1.1 for δ15 N. BSIMM estimation supported a significant increase in the contribution of marine resources to human diet. DISCUSSION: The results provide the first biomolecular evidence for a dietary revolution that is not evidenced in contemporaneous historical accounts. We find that society transitioned from a largely agro-pastoral economy under Islamic rule to one characterized by a new focus on marine resources under later Christian rule. This economic change led to the naissance of the marine economy that went on to characterize the early-modern period in Portugal and its global expansion.