RESUMEN

Mass spectrometry can gain analytical interpretability by studying complementarity and synergy between the data obtained by the same technique. To explore its potential in an untargeted metabolomic application, the objective of this work was to obtain organic and aqueous coffee extracts of three coffee Canephora groups produced in Brazil with distinctive aspects: geographical origin and botanical variety. Aqueous and organic extracts of roasted coffee beans were analyzed by direct infusion electrospray ionization mass spectrometry. Due to the large number of samples, the injector of the liquid chromatography system was used to automate the analysis. The column was removed, and a peak tube was added to connect the system directly to the mass spectrometer to inject both polar and nonpolar fractions of the coffee extracts individually. The technique provided characteristic fingerprinting mass spectra that not only allowed for differentiation of geographical origins but also between robusta and conilon botanical varieties. The mass spectra of the organic and water extracts represented two separate data blocks to be analyzed by the ComDim-ICA multi-block data analysis method. While the classical ComDim is based on applying PCA to the iteratively reweighted concatenated matrices, in the ComDim-ICA, the factorization is done using independent components analysis, which promotes specific improvements since it is based on extracting components that are statistically independent of one another. The results highlighted by ComDim-ICA show that both water and organic extracts contributed with important ions to the characterization of the coffee composition. However, the results revealed a high variability of metabolomic composition within each botanical variety (Robusta Amazônico and Conilon Capixaba) and geographical provenance (Rondônia indigenous-1, Rondônia non-indigenous-2 and Espírito Santo-3). Even so, water mass spectra differentiated the botanical variety Conilon from Robusta based on significant ions related to trigonelline, caffeic acid, caffeoylquinic acid, and methylpyridinium; both water and organic mass spectra differentiated Rondônia indigenous from Rondônia non-indigenous and Espírito Santo Conilon based on significant ions related to benzoic acid, pentose, coumaric acid, caffeine in the organic extract and malonic acid, pentose, caffeoylquinic acid, methyl pyridinium, caffeine, and sucrose present in the water extract. With the proposed approach acquiring ion fingerprints of different coffee extracts and their subsequent analysis by ComDim-ICA, new complementary chemical aspects of Brazilian Coffea canephora were put in evidence.

Asunto(s)

Coffea , Extractos Vegetales , Coffea/química , Brasil , Extractos Vegetales/química , Extractos Vegetales/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Análisis de Componente Principal , Geografía , Café/química , Espectrometría de Masas/métodos

RESUMEN

AIM: Primary Signet Ring Cell Carcinoma (SRCC) of the bladder accounts for only 1%‒4% of all bladder malignancies. To date, few studies have been conducted to investigate the characteristics of SRCC. This study aimed to investigate the clinical features and treatments of SRCC and explore the independent risk factors of survival in SRCC patients. PATIENTS AND METHODS: A retrospective study was conducted on 32 eligible patients. The survival rate was calculated with the Kaplan-Meier method, and the COX proportional hazards model was used to investigate the independent risk factors of prognosis. RESULTS: In the present study, the 1-year and 2-year survival rates of SRCC patients were 53.1% and 9.4%, respectively. The TNM stage, tumor differentiation, and metastasis after treatment were risk factors for the prognosis of SRCC patients (p < 0.05), while surgical treatment, chemotherapy, and positive GATA3 expression were protective for prognosis (p < 0.05). Multivariate analysis showed that GATA3 was an independent protective factor for prognosis (p < 0.05), and T-stage was an independent risk factor (p < 0.05). CONCLUSIONS: Primary SRCC of the bladder is highly malignant and has a poor prognosis. Its clinical and imaging findings are usually non-specific. Early radical cystectomy and postoperative adjuvant systemic chemotherapy are helpful to improve the survival rate. T-stage is an independent risk factor for survival, and positive GATA3 expression is protective for primary SRCC of the bladder.

Asunto(s)

Carcinoma de Células en Anillo de Sello , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Adulto , Estadificación de Neoplasias , Estimación de Kaplan-Meier , Pronóstico , Tasa de Supervivencia , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años

RESUMEN

Pharmaceutically active compounds (PhACs) have been detected in several aquatic compartments, which has been of environmental concern since PhACs can cause adverse effects on the aquatic ecosystem at low concentrations. Despite the variety of PhACs detected in surface water, ecotoxicological studies are non-existent for many of them, mainly regarding their mixture. In addition, water bodies can continuously receive the discharge of raw or treated wastewater with micropollutants. Thus, PhACs are subject to mixture and interactions, potentiating or reducing their toxicity. Therefore, the present study evaluated the toxicity on Aliivibrio fischeri of seven PhACs, which still needs to be explored in the literature. The effects were evaluated for the PhACs individually and for their binary and tertiary mixture. Also, the experimental effects were compared with the concentration addition (CA) and independent action (IA) models. Finally, an environmental risk assessment was carried out. Fenofibrate (FEN), loratadine (LOR), and ketoprofen (KET) were the most toxic, with EC50 of 0.32 mg L-1, 6.15 mg L-1 and 36.8 mg L-1, respectively. Synergistic effects were observed for FEN + LOR, KET + LOR, and KET + FEN + LOR, showing that the CA and IA may underestimate the toxicity. Environmental risks for KET concerning algae, and LOR e 17α-ethynylestradiol (EE2) for crustaceans and fish were high for several locations. Besides, high removals by wastewater treatment technologies are required to achieve the concentrations necessary for reducing KET and LOR risk quotients. Thus, this study contributed to a better understanding of the toxic interactions and environmental risks of PhACs.

Asunto(s)

Aliivibrio fischeri , Ecotoxicología , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/efectos de los fármacos , Medición de Riesgo , Preparaciones Farmacéuticas/análisis , Pruebas de Toxicidad

RESUMEN

Introduction: Medications are a fundamental part of the treatment of multiple pathologies. However, despite their benefits, some are considered potentially inappropriate medications for older people given their safety profile. Epidemiological data differences related to potentially inappropriate medications make it difficult to determine their effects on elderly people. Objective: To estimate the prevalence and types of potentially inappropriate medications using the 2019 Beers Criteria® in a cohort of adults older than 65 years. Materials and methods: We performed an observational, multicenter, retrospective, longitudinal study of a four-year follow-up of potentially inappropriate medications in community-dwelling older adults. Results: We followed 820 participants from five cities for four years (2012-2016) and evaluated them in three different moments (m1 = 2012, m2 = 2014, and m3 = 2016). The average age was 69.07 years, and 50.9% were women. The potentially inappropriate medication prevalence in the participants was 40.24%. The potentially inappropriate medications' mean among the studied subjects in the first moment was 1.65 (SD = 0.963), in the second was 1.73 (SD = 1.032), and in the third was 1.62 (SD = 0.915). There were no statistical differences between measurements (Friedman test, value = 0.204). The most frequent potentially inappropriate medications categories were gastrointestinal (39.4%), analgesics (18.8%), delirium-related drugs (15.4%), benzodiazepines (15.2%), and cardiovascular (14.2%). Conclusions: About half of the population of the community-dwelling older adults had prescriptions of potentially inappropriate medications in a sustained manner and without significant variability over time. Mainly potentially inappropriate medications were gastrointestinal and cardiovascular drugs, analgesics, delirium-related drugs, and benzodiazepines.

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Introducción. Los fármacos son parte fundamental del tratamiento de múltiples enfermedades. Sin embargo, a pesar de sus beneficios, algunos se consideran medicamentos potencialmente inapropiados en adultos mayores, dado su perfil de seguridad. Las diferencias en los datos epidemiológicos relacionados con los medicamentos potencialmente inapropiados dificultan el establecimiento de sus efectos en adultos mayores. Objetivo. Estimar la prevalencia longitudinal y los tipos de medicamentos potencialmente inapropiados, utilizando los criterios Beers® del 2019 en una cohorte de adultos mayores de 65 años. Materiales y métodos. Se realizó un estudio observacional, multicéntrico, retrospectivo y longitudinal, de cuatro años de seguimiento de los medicamentos potencialmente inapropiados en adultos mayores de la comunidad. Resultados. Se evaluaron 820 participantes de cinco ciudades durante cuatro años (2012 a 2016) en tres momentos (m1: 2012, m2: 2014 y m3; 2016). La edad promedio fue de 69,07 años y el 50,9 % eran mujeres. La prevalencia de medicamentos potencialmente inapropiados en los participantes fue del 40,24 %. El promedio de estos medicamentos entre los sujetos estudiados en el primer momento fue de 1,65 (DE = 0,963), en el segundo fue de 1,73 (DE = 1,032) y en el tercero fue de 1,62 (DE = 0,915). No hubo diferencias estadísticas entre las mediciones (prueba de Friedman, p = 0,204). Las categorías de los medicamentos potencialmente inapropiados más frecuentes fueron: gastrointestinales (39,4 %), analgésicos (18,8 %), relacionados con delirium (15,4 %), benzodiacepinas (15,2 %) y cardiovasculares (14,2 %). Conclusiones. En cerca de la mitad de la población de adultos mayores de la comunidad, se prescribieron medicamentos potencialmente inapropiados de manera sostenida y sin variabilidad importante en el tiempo. Los más recetados fueron aquellos para tratar malestares gastrointestinales y cardiovasculares, analgésicos, para el delirium y benzodiacepinas.

Asunto(s)

Vida Independiente , Lista de Medicamentos Potencialmente Inapropiados , Humanos , Anciano , Femenino , Masculino , Estudios Longitudinales , Estudios Retrospectivos , Anciano de 80 o más Años , Prescripción Inadecuada/estadística & datos numéricos , Prevalencia , Benzodiazepinas/uso terapéutico , Benzodiazepinas/efectos adversos

RESUMEN

Independent vector analysis (IVA) can be viewed as an extension of independent component analysis (ICA) to multiple datasets. It exploits the statistical dependency between different datasets through mutual information. In the context of motor imagery classification based on electroencephalogram (EEG) signals for the brain-computer interface (BCI), several methods have been proposed to extract features efficiently, mainly based on common spatial patterns, filter banks, and deep learning. However, most methods use only one dataset at a time, which may not be sufficient for dealing with a multi-source retrieving problem in certain scenarios. From this perspective, this paper proposes an original approach for feature extraction through multiple datasets based on IVA to improve the classification of EEG-based motor imagery movements. The IVA components were used as features to classify imagined movements using consolidated classifiers (support vector machines and K-nearest neighbors) and deep classifiers (EEGNet and EEGInception). The results show an interesting performance concerning the clustering of MI-based BCI patients, and the proposed method reached an average accuracy of 86.7%.

Asunto(s)

Interfaces Cerebro-Computador , Electroencefalografía , Movimiento , Máquina de Vectores de Soporte , Humanos , Electroencefalografía/métodos , Movimiento/fisiología , Imaginación/fisiología , Procesamiento de Señales Asistido por Computador , Algoritmos

RESUMEN

A T-cell-independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity, but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 month old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cell and plasma cell sub-populations by flow cytometry and molecular factors related to class switch recombination [Thymic Stromal Lymphopoietin (TSLP), A Proliferation-Inducing Ligand (APRIL), B Cell Activating Factor (BAFF), inducible nitric oxide synthase (iNOS), and retinal dehydrogenase (RDH)] and the synthesis of IgA [α-chain, interleukin (IL)-6, IL-21, and Growth Factor-ß (TGF-ß)]; and epithelial cells evaluated IgA transitosis [polymeric immunoglobulin receptor (pIgR), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-4] by the RT-qPCR technique. The results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANOVA, and p < 0.05 was considered to be a statistically significant difference. Under senescence conditions, MAE promoted the B cell and IgA+ B cells and APRIL, which may improve the intestinal response and ameliorate the inflammatory environment associated presumably with the downmodulation of pro-inflammatory mediators involved in the upmodulation of pIgR expression. Data suggested that MAE improved IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging.

Asunto(s)

Envejecimiento , Homeostasis , Inmunoglobulina A , Ratones Endogámicos BALB C , Condicionamiento Físico Animal , Animales , Inmunoglobulina A/metabolismo , Inmunoglobulina A/inmunología , Ratones , Envejecimiento/inmunología , Citocinas/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Factor Activador de Células B/metabolismo , Factor Activador de Células B/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Intestino Delgado/inmunología , Intestino Delgado/metabolismo , Masculino , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética

RESUMEN

BACKGROUND: Metformin, a widely prescribed antidiabetic drug, has shown several promising effects for cancer treatment. These effects have been shown to be mediated by dual modulation of the AMPK-mTORC1 axis, where AMPK acts upstream of mTORC1 to decrease its activity. Nevertheless, alternative pathways have been recently discovered suggesting that metformin can act through of different targets regulation. METHODS: We performed a transcriptome screening analysis using HeLa xenograft tumors generated in NOD-SCID mice treated with or without metformin to examine genes regulated by metformin. Western Blot analysis, Immunohistochemical staining, and RT-qPCR were used to confirm alterations in gene expression. The TNMplot and GEPIA2 platform were used for in silico analysis of genes found up-regulated by metformin, in cervical cancer patients. We performed an AMPK knock-down using AMPK-targeted siRNAs and mTOR inhibition with rapamycin to investigate the molecular mechanisms underlying the effect of metformin in cervical cancer cell lines. RESULTS: We shown that metformin decreases tumor growth and increased the expression of a group of antitumoral genes involved in DNA-binding transcription activator activity, hormonal response, and Dcp1-Dcp2 mRNA-decapping complex. We demonstrated that ZFP36 could act as a new molecular target increased by metformin. mTORC1 inhibition using rapamycin induces ZFP36 expression, which could suggest that metformin increases ZFP36 expression and requires mTORC1 inhibition for such effect. Surprisingly, in HeLa cells AMPK inhibition did not affect ZFP36 expression, suggesting that additional signal transducers related to suppressing mTORC1 activity, could be involved. CONCLUSIONS: These results highlight the importance of ZFP36 activation in response to metformin treatment involving mTORC1 inhibition.

Asunto(s)

Diana Mecanicista del Complejo 1 de la Rapamicina , Metformina , Neoplasias del Cuello Uterino , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Metformina/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Femenino , Animales , Ratones , Células HeLa , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones SCID , Ratones Endogámicos NOD , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología

RESUMEN

Abstract Introduction. Medications are a fundamental part of the treatment of multiple pathologies. However, despite their benefits, some are considered potentially inappropriate medications for older people given their safety profile. Epidemiological data differences related to potentially inappropriate medications make it difficult to determine their effects on elderly people. Objective. To estimate the prevalence and types of potentially inappropriate medications using the 2019 Beers Criteria® in a cohort of adults older than 65 years. Materials and methods. We performed an observational, multicenter, retrospective, longitudinal study of a four-year follow-up of potentially inappropriate medications in community-dwelling older adults. Results. We followed 820 participants from five cities for four years (2012-2016) and evaluated them in three different moments (m1 = 2012, m2 = 2014, and m3= 2016). The average age was 69.07 years, and 50.9% were women. The potentially inappropriate medication prevalence in the participants was 40.24%. The potentially inappropriate medications' mean among the studied subjects in the first moment was 1.65 (SD = 0.963), in the second was 1.73 (SD = 1.032), and in the third was 1.62 (SD = 0.915). There were no statistical differences between measurements (Friedman test, value = 0.204). The most frequent potentially inappropriate medications categories were gastrointestinal (39.4%), analgesics (18.8%), delirium-related drugs (15.4%), benzodiazepines (15.2%), and cardiovascular (14.2%). Conclusions. About half of the population of the community-dwelling older adults had prescriptions of potentially inappropriate medications in a sustained manner and without significant variability over time. Mainly potentially inappropriate medications were gastrointestinal and cardiovascular drugs, analgesics, delirium-related drugs, and benzodiazepines.

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Resumen Introducción. Los fármacos son parte fundamental del tratamiento de múltiples enfermedades. Sin embargo, a pesar de sus beneficios, algunos se consideran medicamentos potencialmente inapropiados en adultos mayores, dado su perfil de seguridad. Las diferencias en los datos epidemiológicos relacionados con los medicamentos potencialmente inapropiados dificultan el establecimiento de sus efectos en adultos mayores. Objetivo. Estimar la prevalencia longitudinal y los tipos de medicamentos potencialmente inapropiados, utilizando los criterios Beers® del 2019 en una cohorte de adultos mayores de 65 años. Materiales y métodos. Se realizó un estudio observacional, multicéntrico, retrospectivo y longitudinal, de cuatro años de seguimiento de los medicamentos potencialmente inapropiados en adultos mayores de la comunidad. Resultados. Se evaluaron 820 participantes de cinco ciudades durante cuatro años (2012 a 2016) en tres momentos (m1: 2012, m2: 2014 y m3; 2016). La edad promedio fue de 69,07 años y el 50,9 % eran mujeres. La prevalencia de medicamentos potencialmente inapropiados en los participantes fue del 40,24 %. El promedio de estos medicamentos entre los sujetos estudiados en el primer momento fue de 1,65 (DE = 0,963), en el segundo fue de 1,73 (DE = 1,032) y en el tercero fue de 1,62 (DE = 0,915). No hubo diferencias estadísticas entre las mediciones (prueba de Friedman, p = 0,204). Las categorías de los medicamentos potencialmente inapropiados más frecuentes fueron: gastrointestinales (39,4 %), analgésicos (18,8 %), relacionados con delirium (15,4 %), benzodiacepinas (15,2 %) y cardiovasculares (14,2 %). Conclusiones. En cerca de la mitad de la población de adultos mayores de la comunidad, se prescribieron medicamentos potencialmente inapropiados de manera sostenida y sin variabilidad importante en el tiempo. Los más recetados fueron aquellos para tratar malestares gastrointestinales y cardiovasculares, analgésicos, para el delirium y benzodiacepinas.

RESUMEN

Assessing membrane protein stability is among the major challenges in protein science due to their inherent complexity, which complicates the application of conventional biophysical tools. In this work, sodium dodecyl sulfate-induced denaturation of AfCopA, a Cu(I)-transport ATPase from Archaeoglobus fulgidus, was explored using a combined model-free spectral phasor analysis and a model-dependent thermodynamic analysis. Decrease in tryptophan and 1-anilino-naphthalene-8-sulfonate fluorescence intensity, displacements in the spectral phasor space, and the loss of ATPase activity were reversibly induced by this detergent. Refolding from the SDS-induced denatured state yields an active enzyme that is functionally and spectroscopically indistinguishable from the native state of the protein. Phasor analysis of Trp spectra allowed us to identify two intermediate states in the SDS-induced denaturation of AfCopA, a result further supported by principal component analysis. In contrast, traditional thermodynamic analysis detected only one intermediate state, and including the second one led to overparameterization. Additionally, ANS fluorescence spectral analysis detected one more intermediate and a gradual change at the level of the hydrophobic transmembrane surface of the protein. Based on this evidence, a model for acquiring the native structure of AfCopA in a membrane-like environment is proposed.

Asunto(s)

Archaeoglobus fulgidus , Proteínas de la Membrana , Desnaturalización Proteica , Dodecil Sulfato de Sodio , Termodinámica , Dodecil Sulfato de Sodio/química , Dodecil Sulfato de Sodio/farmacología , Archaeoglobus fulgidus/enzimología , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/metabolismo , Espectrometría de Fluorescencia , Estabilidad Proteica , Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , Naftalenosulfonatos de Anilina/química , Naftalenosulfonatos de Anilina/metabolismo , Triptófano/química , Triptófano/metabolismo , Cobre/química , Cobre/metabolismo , Pliegue de Proteína , Conformación Proteica

RESUMEN

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.

Asunto(s)

Metabolómica , Programas Informáticos , Reproducibilidad de los Resultados , Flujo de Trabajo , Metabolómica/métodos , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos

RESUMEN

This work provides a detailed multi-component analysis of aromaticity in monosubstituted (X = CH3, C H 2 - , C H 2 + , NH2, NH-, NH+, OH, O-, and O+) and para-homodisubstituted (X = CH3, CH2, NH2, NH, OH, and O) benzene derivatives. We investigate the effects of substituents using single-reference (B3LYP/DFT) and multireference (CASSCF/MRCI) methods, focusing on structural (HOMA), vibrational (AI(vib)), topological (ELFπ), electronic (MCI), magnetic (NICS), and stability (S0-T1 splitting) properties. The findings reveal that appropriate π-electron-donating and π-electron-accepting substituents with suitable size and symmetry can interact with the π-system of the ring, significantly influencing π-electron delocalization. While the charge factor has a minimal impact on π-electron delocalization, the presence of a pz orbital capable of interacting with the π-electron delocalization is the primary factor leading to a deviation from the typical aromaticity characteristics observed in benzene.

RESUMEN

Löwenstein's avoidance rule in aluminosilicates is reinterpreted on the basis of the fourth Pauling rule. It is shown that avoidance of Si-O-Si bridges may account for avoidance of Al-O-Al bridges. In view of this interpretation, it is proposed that the most favourable distributions of cations entering in substitution of silicon in the framework are associated to maximal independent sets of the respective 3-periodic nets. Among all possible solutions, only those with maximal symmetry are realized. The applicability of the concept is demonstrated for a few natural tectosilicates, which have been analysed through the prism of their labelled quotient graph.

RESUMEN

PURPOSE: To investigate the potential clinical importance of continuing immunotherapy beyond progression in patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: The data of patients with aNSCLC who experienced progressive disease after receiving first-line immunotherapy plus chemotherapy were collected from multiple centers for the period from January 1, 2018 to May 31, 2022. According to the second-line treatment, the patients were classified into two groups: the continuation of immunotherapy beyond progression (CIBP) group and the discontinuation of immunotherapy beyond progression (DIBP) group. The efficacy and safety of the treatment were compared between the groups. RESULTS: Overall, data from 169 patients were analyzed; 93 patients were enrolled in the CIBP group and 76 patients were in the DIBP group. The median second-line progression-free survival was 5.5 months in the CIBP group, which for the DIBP group was 3.4 (p = 0.011). The median overall survival of the CIBP group was 13.3 months, whereas that of the DIBP group was 8.8 months (p = 0.031). The disease control rate of the CIBP group (79.57%) was observably higher than that of the DIBP group (64.47%; p = 0.028). Among patients who responded better (complete or partial response) to prior therapy, the median progression-free survival was 5.5 months and 3.3 months in the CIBP and DIBP groups respectively (p = 0.022), and the median overall survival was 14.8 months and 8.8 months in the CIBP and DIBP groups respectively (p = 0.046). CONCLUSIONS: Continuing immunotherapy as a second-line treatment could be beneficial to the survival of patients with aNSCLC with disease progression beyond initial chemotherapy combined with immunotherapy.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Progresión de la Enfermedad , Inmunoterapia , Neoplasias Pulmonares , Supervivencia sin Progresión , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Inmunoterapia/métodos , Adulto , Estudios Retrospectivos , Anciano de 80 o más Años , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico

RESUMEN

The flat electronic band has remarkable relevance in the strongly correlated phenomena mainly due to its reduced kinetic energy in comparison to the many-body potential energy. The formation of such bands in cubically structured nanowires is addressed in this article by means of a new independent channel method and a generalized convolution theorem developed for the Green's function including the first, second, and third neighbor interactions. A real-space renormalization method is further applied to address macroscopic-length aperiodic nanowires. We also determined the appearance condition of these flat bands, as well as their degeneracy and robustness in the face of perturbations, such as structural dislocations. Finally, the possible experimental detection of this flat band via the electronic specific heat is analyzed.

RESUMEN

BACKGROUND AND AIMS: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional reports, identified several risk factors associated with the prevalence and incidence of this condition. However, alterations in body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. METHODS: This is a secondary analysis of older adults (≥60 years) derived from the study "Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)", a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. RESULTS: The cohort included 241 subjects. The average age was 75.6 ± 7.8 years, and 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in those with an excess fat mass, even after adjusting for several covariates. Regarding total lean tissue, the unadjusted model showed that RM was more likely to occur in men and women with a low TLT by the TLTI classification, compared to the normal group. However, after adjusting for several covariates (models 1 and 2), the association lost significance. Results on the association between gait speed and RM showed that this condition was also more likely to occur in subjects with low gait speed, according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. CONCLUSIONS: RM diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, and a significant association emerged between low gait speed and RM after 4.1 years of follow-up in these community-dwelling older adults. These results confirm the association between some alterations of body composition and impaired physical performance with the risk of malnutrition and highlight that excess fat mass and low gait speed precede the risk of malnutrition, not vice versa.

Asunto(s)

Desnutrición , Sarcopenia , Masculino , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Vida Independiente , Velocidad al Caminar , Estudios de Cohortes , Fuerza de la Mano , Estudios Prospectivos , Incidencia , Estudios Transversales , Desnutrición/complicaciones , Desnutrición/epidemiología , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Evaluación Geriátrica/métodos

RESUMEN

The use of the USP IV apparatus (flow-through cell) has gained acceptance in recent years due to its versatility and ability to discriminate due to its hydrodynamic conditions. Therefore, the objective of the present study was to develop a discriminative dissolution method in the USP IV apparatus using the open-loop configuration, as well as to propose a method to compare non-cumulative dissolution profiles obtained in the open-loop configuration considering kinetic parameters and validate its predictive power through its comparison with independent and dependent methods using five commercial immediate-release tablet drugs (one reference drug and four generic drugs) of metoprolol tartrate as a model drug. The comparison of the non-accumulated dissolution profiles consisted of determining the geometric ratio of Cmax, AUC0∞, AUC0Cmax, and Tmax (kinetic parameters) of the generic/reference drugs, whereby generic drugs "C" and "D" presented the highest probability of similarity since their 90% confidence intervals were included, or they were very close to the acceptance interval (80.00-125.00%). These results were consistent with the f2, bootstrap f2, and dissolution efficiency approaches (independent models). In conclusion, the proposed comparison method can be an important tool to establish similarity in dissolution profiles and to facilitate the development/selection of new formulations and positively ensure bioequivalence in clinical studies.

RESUMEN

Introducción: La atención a domicilio de adultos mayores dependientes es una tarea compleja que requiere de profesionales de enfermería altamente capacitados. Sin embargo, las condiciones laborales adversas y la falta de atención al cuidado de sí mismo ponen en riesgo su salud y bienestar, así como la calidad del cuidado que brindan. Objetivo: Describir las condiciones de trabajo y el cuidado de sí en profesionales de enfermería en la atención domiciliaria de adultos mayores dependientes. Metodología: Investigación cualitativa de diseño narrativo utilizando la teoría del cuidado de sí de Michel Foucault. Muestreo por bola de nieve. Criterios de selección: ser enfermero(a) de atención domiciliaria, tener bajo su cuidado a adultos mayores dependientes y firmar el consentimiento informado. Recolección de datos mediante entrevistas semiestructuradas, grabadas y transcritas textualmente para ser analizadas con ayuda del software ATLAS.ti. Participantes: 9 profesionales de enfermería domiciliaria independiente. Resultados: Emergieron 2 categorías: 1) La familia en el cuidado y 2) El lado doloroso del cuidado. Conclusiones: Además de las habilidades de comunicación eficaz para solicitar las adaptaciones arquitectónicas de la vivienda y la colaboración de los familiares, se hace evidente que cuando se usan las tecnologías de la teoría de Michel Foucault, se promueve el cuidado de sí de la enfermera. Discusión: La capacidad para tomar conciencia sumado al pensamiento crítico, son necesarios para tener el poder y autonomía sobre las decisiones que se llevan a cabo en el trabajo, reduciendo riesgos e injusticias en el ámbito que se encuentre y promover el cuidado de sí.

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Introduction: Home care of dependent older adults is a complex task that requires highly trained nursing professionals. However, adverse working conditions and lack of attention to self-care jeopardize their health and well-being, as well as the quality of care they provide. Objective: To describe the working conditions and self-care of nursing professionals in the home care of dependent older adults. Methodology: Qualitative research of narrative design using Michel Foucault's theory of self-care. Snowball sampling. Selection criteria: to be a home care nurse, to have dependent older adults under his/her care and to sign the informed consent form. Data collection through semi-structured interviews, recorded and transcribed verbatim for analysis using ATLAS.ti software. Participants: 9 independent home nursing professionals. Results: 2 categories emerged: 1) The family in caregiving and 2) The painful side of caregiving. Conclusions: In addition to effective communication skills to request architectural adaptations of the home and the collaboration of family members, it is evident that when the technologies of Michel Foucault's theory are used, the nurse's self-care is promoted. Discussion: The ability to be aware and critical thinking are necessary to have power and autonomy over the decisions that are carried out at work, reducing risks and injustices in the field and promoting self-care.

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Introdução: O atendimento domiciliar de idosos dependentes é uma tarefa complexa que exige profissionais de enfermagem altamente treinados. No entanto, as condições de trabalho adversas e a falta de atenção ao autocuidado prejudicam sua saúde e bem-estar, bem como a qualidade do atendimento que prestam. Objetivo: descrever as condições de trabalho e o autocuidado dos profissionais de enfermagem na assistência domiciliar a idosos dependentes. Metodologia: Pesquisa qualitativa com um projeto narrativo usando a teoria do autocuidado de Michel Foucault. Amostragem em bola de neve. Critérios de seleção: ser enfermeiro de atendimento domiciliar, estar cuidando de idosos dependentes e assinar o termo de consentimento livre e esclarecido. Coleta de dados por meio de entrevistas semiestruturadas, gravadas e transcritas literalmente para análise usando o software ATLAS.ti. Participantes: 9 profissionais independentes de enfermagem domiciliar. Resultados: Surgiram duas categorias: 1) A família no cuidado e 2) O lado doloroso do cuidado. Conclusões: Além de habilidades de comunicação eficazes para solicitar adaptações arquitetônicas na residência e a colaboração dos familiares, fica evidente que, quando as tecnologias da teoria de Michel Foucault são utilizadas, o autocuidado do enfermeiro é promovido. Discussão: A capacidade de conscientização e o pensamento crítico são necessários para ter poder e autonomia sobre as decisões tomadas no trabalho, reduzindo os riscos e as injustiças no campo e promovendo o autocuidado.

Asunto(s)

Humanos

RESUMEN

BACKGROUND: Malignant cells adopt anoikis resistance to survive anchorage-free stresses and initiate cancer metastasis. It is still unknown how varying periods of anchorage loss contribute to anoikis resistance, cell migration, and metabolic reprogramming of cancerous cells. RESULTS: Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. While the prolonged anchorage-free lifetime was responsible for the increased aggressive feature of survival cells to perform rapid 3-dimensional migration during the first 3 h of a transwell assay, no significant influence was observed with 2-dimensional surface migration detected at 12 and 24 h by a wound-healing method. Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, ß-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. Based on significance values, enrichment ratios, and impact scores of all metabolites and their associated pathways, three principal metabolic activities (non-standard amino acid metabolism, cell membrane biosynthesis, and oxidative stress response) offered potential links with anoikis resistance. CONCLUSIONS: These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anoicis , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Metabolómica

RESUMEN

This paper introduces a new method of determining the independence ratio of periodic nets, based on the observation that, in any maximum independent set of the whole net, be it periodic or not, the vertices of every unit cell should constitute an independent set, called here a configuration. For 1-periodic graphs, a configuration digraph represents possible sequences of configurations of the unit cell along the periodic line. It is shown that maximum independent sets of the periodic graph are based on directed cycles with the largest ratio. In the case of 2-periodic nets, it is necessary to draw a different configuration digraph for each crystallographic direction defining a linkage between neighbouring cells, a concept known as a binary relational system. The two possible systems are analysed in this paper: \overrightarrow{\bf{sql}} is associated to nets displaying linkages between unit cells along the directions 10 and 01, and \overrightarrow{\bf{hxl}} is associated to nets also displaying linkages between cells along the direction 11. For both kinds of nets, a maximum independent set is obtained as a homomorphic image from \overrightarrow{\bf{sql}} or \overrightarrow{\bf{hxl}} to the respective configuration system. The method is illustrated with some of the 2-periodic nets listed on the Reticular Chemistry Structure Resource site; it is shown that it provides a rigorous solution to the case of the net sdh that was not satisfactorily solved in Part II [Moreira de Oliveira, de Abreu Mendes & Eon (2022). Acta Cryst. A78, 115-127]. The method is extended to relational systems based on non-translational symmetry operations. The successive steps are then summarized and a simple application to the 3-periodic net qtz is discussed; analysis of zeolites and aluminosilicates may proceed along the same lines. It is shown that the new method enables the analysis of disordered distributions in periodic nets.

RESUMEN

Resumen En el ámbito de la discapacidad intelectual, el desarrollo de una vida independiente se ha configurado como un derecho humano y civil que permite a estas personas articular planes de vida deseados. Esta investigación analiza, mediante un estudio de caso, los significados que un grupo asesor compuesto por ocho personas adultas con discapacidad intelectual tiene sobre el concepto de vida independiente en el contexto chileno. Para la recopilación de los datos se diseñó una entrevista grupal semiestructurada acompañada de moodboards que facilitaron la verbalización de las respuestas. Sobre los relatos obtenidos a partir de las entrevistas se realizó un análisis de contenido temático. Los resultados muestran cómo el desempeño de una actividad laboral remunerada o el establecimiento de relaciones afectivas sólidas se conforman como elementos imprescindibles para la independencia personal. La dificultad para ser económicamente independientes o la falta de accesibilidad en el entorno laboral se identifican también como principales barreras para la concreción de este derecho. Igualmente, se destaca el rol que desempeñan la pareja y las amistades como figuras de apoyo constante a la independencia y al empoderamiento personal. Estos resultados sugieren algunas orientaciones para la planificación de intervenciones sobre este constructo, las cuales deben procurar la adquisición de habilidades que fortalezcan la capacidad de autocuidado de este colectivo, promover el incremento de oportunidades para la realización de elecciones significativas en el ámbito laboral, personal y comunitario, y adaptarse a los espacios en los que se desenvuelven las personas con discapacidad intelectual en la edad adulta.

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Abstract In the field of intellectual disability, the development of an independent life has been configured as a human and civil right that allows these people to articulate desired life plans. Despite the advances, at the international level, research on aspects related to independent living in people with intellectual disabilities continues to be very scarce. Generally, the approaches to the study of this construct are based on broader investigations dedicated to evaluating the levels of quality of life or self-determination of this population in residential services or sheltered housing. Precisely, this study analyzes, through a case study, the meanings that an advisory group made up of eight adults with intellectual disabilities has on the concept of independent living in the Chilean context in order, on the one hand, to identify relevant elements for the definition of the construct from the perceptions and experiences of this population; and on the other, to propose guidelines at various levels that allow progress in the realization of this right. To collect the data, a semi-structured group interview was designed whose questions were grouped around four themes: previous conceptions of the participants about the construct of independent life, satisfaction with life and possibilities of the context for the development of personal independence, role of family, friendship and partner in independent life, and opportunities of the work context for the achievement of personal independence. During the interview, another strategy was incorporated in which visual language gained more relevance. Specifically, a set of ten moodboards were used that allowed participants to delve into the different topics addressed. The results of the code validation process were calculated using Krippendorff's alpha statistics (.954) and Cohen's kappa (.953), which showed a high level of inter-judge agreement. As a result of this process, categories (N = 6) and subcategories (N = 17) were established. The results show how various needs, barriers and facilitators for the development of independent life are identified from the interviews of the interviewees. Among the main needs is the performance of a paid work activity or the establishment of solid affective relationships. With regard to the barriers that hinder personal independence, the most notorious are related to the difficulty of being financially independent or to the lack of accessibility in the work environment. Regarding the elements that facilitate the development of an independent life, the role of the couple stands out as a constant figure of support for independence and personal empowerment. These results suggest some guidelines for planning interventions on this construct. Among others, they should seek the acquisition of skills that strengthen the self-care capacity of this group; should promote increased opportunities for making meaningful choices in the workplace, personal and community; and they must adapt to the spaces in which people with intellectual disabilities operate in adulthood. On the other hand, it is assumed that one of the main limitations of this research is that the results are not generalizable. However, this study has some strengths. Among others, it contributes to enriching the bulk of research on independent living, this being an aspect barely addressed in the literature. It also complements the results of other research regarding the elements that can condition the development of skills for personal independence. This allows for the design of interventions that provide opportunities for independent living based on the felt needs of these people. In addition, it raises future lines of research related, for example, to the importance of the informed choice of the residential environment or to the study of the possibilities of the digital world as an incident phenomenon in the acquisition of skills for personal independence.