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1.
Dig Dis ; 42(3): 257-264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38452742

RESUMEN

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Pancreatitis , Sistema de Registros , Humanos , Femenino , Pancreatitis/inducido químicamente , Pancreatitis/genética , Masculino , Adulto , Estudios de Casos y Controles , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Factores de Riesgo , Variación Genética , Mercaptopurina/efectos adversos , Mercaptopurina/uso terapéutico
2.
Int J Equity Health ; 23(1): 60, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500124

RESUMEN

In May 2012, the 65th World Health Assembly (WHA) approved six global nutrition targets by 2025 aimed to reduce stunting in children under five by 40%, maintain childhood wasting below 5%, halt obesity, cut anemia in women by 50%, lower low birth weight prevalence by 30%, and increase exclusive breastfeeding (EBF) within the first 6 months to 50%. These targets were extended to 2030, with all of them remaining as originally planned, but the EBF one (increased to 70%), wasting and overweight (both objectives set to eliminate them to negligible concern). Mexico is projected to achieve only one of the six nutrition targets (wasting) by 2025, falling far short of the stunting, low birth weight, anemia, and exclusive breastfeeding for the updated goals by 2030. This letter to the editor describes the most recent prevalence of malnutrition among mothers and children in Mexico. It discusses the challenges pregnant women and children under five years of age face exercising their right to good food, nutrition, and development. The authors reflect on the urgent need to make structural changes to achieve the global nutrition targets by 2030, highlighting the paramount importance of addressing the profound structural obstacles in Mexico and how Mexico's government must prioritize poverty reduction, reduce the marked inequalities, enhance the quality of nutritional care and healthcare infrastructure, and implement climate-resilient agricultural practices to address this pressing issue.


Asunto(s)
Anemia , Desnutrición , Niño , Femenino , Humanos , Embarazo , Lactante , Preescolar , México/epidemiología , Estado Nutricional , Desnutrición/prevención & control , Desnutrición/epidemiología , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/prevención & control , Anemia/epidemiología , Prevalencia
3.
Int J Equity Health ; 23(1): 35, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388936

RESUMEN

BACKGROUND: Maternal and child malnutrition represents a public health problem in Mexico Primary care (PC) is responsible for introducing women and children under five to the health system, detecting diseases on time, and providing medical services, including pharmacological treatment if necessary. Providing these services with quality is essential to improve maternal and child health. This study evaluated the quality of nutritional care during preconception, pregnancy, postpartum, infancy, and preschool age at the PC health units across six Mexican states between 2020 and 2021. METHODS: We conducted a cross-sectional study with a mixed approach in units of the Secretary of Health to assess the quality of nutritional care during preconception, pregnancy, postpartum, childhood, and preschool age. The level of quality was calculated by the percentage of compliance with 16 indicators that integrated a Quality Index of Maternal and Child Nutritional Care (ICANMI, by its Spanish acronym). Compliance by indicator, by life stage, and overall was categorized using the following cut-off points: poor quality (≤ 70%), insufficient quality (71-89%), and good quality (≥ 90%). The perceptions of the barriers and facilitators that affect maternal and child nutrition were evaluated through semi-structured interviews with health professionals (HP) and users. All qualitative instruments were developed with a gender and intercultural perspective. RESULTS: Considering the whole sample studied, maternal and child nutritional care quality during the five life stages evaluated was bad (compliance: ≤12%), reflected in the ICANMI, which had a compliance of 8.3%. Principal barriers identified to providing high-quality nutritional care were the lack of knowledge and training of health professionals, shortages of equipment, medicine, personnel, and materials, the disappearance of the social cash transfer program Prospera, the absence of local indigenous language translators to support communication between doctor and patient, and the persistence of machismo and other practices of control over women. CONCLUSIONS: These findings underscore the need for initiatives to improve the quality of nutritional care in PC facilities across Chihuahua, State of Mexico, Veracruz, Oaxaca, Chiapas, and Yucatan. It is necessary for government and health authorities, along with various stakeholders, to collaboratively devise, implement, and assess intercultural and gender-oriented policies and programs geared towards ensuring the health infrastructure and enhancing the training of health professionals to diagnose and treat the prevalence and occurrence of diverse forms of malnutrition in both maternal and child populations.


RESUMEN: ANTECEDENTES: La mala nutrición materno-infantil (MMI) representa un problema de salud pública en México. El primer nivel tiene la respondabilidad de introducir a mujeres y niños menores de 5 años al sistema de salud, detectar oportunamente las enfermedades y brindar servicios médicos incluido el farmacológico de ser necesario. Prestar estos servicios con calidad resulta elemental para mejorar la salud de la población materno-infantil. El objetivo de este estudio fue evaluar la calidad de la atención nutricional durante las etapas de preconcepción, embarazo, posparto, infancia y edad preescolar en centros de salud de seis estados de México entre 2020 y 2021. MéTODOS: Se realizó un estudio transversal con metodología mixta en 95 centros de salud la Secretaría de Salud de México para evaluar la calidad de la atención nutricional durante la preconcepción, el embarazo, el posparto, la infancia y la etapa preescolar. El nivel de calidad se calculó mediante el porcentaje de cumplimiento de 16 indicadores que a su vez integraron un Índice de Calidad de la Atención Nutricional Materno Infantil (ICANMI). El cumplimiento por indicador, etapa de vida y global fue categorizado utilizando los siguientes puntos de corte: mala calidad (≤ 70%), calidad insuficiente (71-89%) y buena calidad (≥ 90%). La percepción sobre las barreras y facilitadores que afectan la atención nutricional materno-infantil fueron identificadas a través de entrevistas semiestructuradas y grupos focales realizadas a profesionales de salud, usuarias y usuarios. Todos los instrumentos cualitativos fueron desarrollados con un enfoque de género e interculturalidad. RESULTADOS: La calidad de la atención nutricional materno infantil durante las cinco etapas de la vida evaluadas fue mala (cumplimiento: ≤12%), mientras que el ICANMI tuvo un cumplimiento de 8.3%. Las principales barreras identificadas para brindar una atención nutricional de alta calidad fueron la falta de conocimiento y capacitación de los profesionales de la salud, la escasez de equipos, medicamentos, personal y materiales, la desaparición del programa social de transferencias monetarias Prospera, la ausencia de una lengua indígena local, entre otros. Así como la persistencia de prácticas como el machismo y otras de control sobre las mujeres. CONCLUSIONES: Estos hallazgos subrayan la necesidad inmediata de implementar iniciativas que mejoren el estándar de atención nutricional en los centros de salud en Chihuahua, Estado de México, Veracruz, Oaxaca, Chiapas y Yucatán. Es necesario que el gobierno y las autoridades sanitarias, junto con diversas partes interesadas, diseñen, implementen y evalúen en colaboración políticas y programas orientados a mejorar la calidad de la atención nutricional, con perspectiva de género e interculturalidad. Este esfuerzo tiene como objetivo mitigar la prevalencia y aparición de diversas formas de desnutrición tanto en la población materna como infantil.


Asunto(s)
Salud Infantil , Desnutrición , Niño , Embarazo , Preescolar , Humanos , Femenino , México , Estudios Transversales , Desnutrición/prevención & control , Atención Primaria de Salud
4.
Cell Mol Neurobiol ; 43(3): 1219-1236, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35917044

RESUMEN

Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) mediated by aberrant auto-reactive immune responses. The current immune-modulatory therapies are unable to protect and repair immune-mediated neural tissue damage. One of the therapeutic targets in MS is the sphingosine-1-phosphate (S1P) pathway which signals via sphingosine-1-phosphate receptors 1-5 (S1P1-5). S1P receptors are expressed predominantly on immune and CNS cells. Considering the potential neuroprotective properties of S1P signaling, we utilized S1P1-GFP (Green fluorescent protein) reporter mice in the cuprizone-induced demyelination model to investigate in vivo S1P - S1P1 signaling in the CNS. We observed S1P1 signaling in a subset of neural stem cells in the subventricular zone (SVZ) during demyelination. During remyelination, S1P1 signaling is expressed in oligodendrocyte progenitor cells in the SVZ and mature oligodendrocytes in the medial corpus callosum (MCC). In the cuprizone model, we did not observe S1P1 signaling in neurons and astrocytes. We also observed ß-arrestin-dependent S1P1 signaling in lymphocytes during demyelination and CNS inflammation. Our findings reveal ß-arrestin-dependent S1P1 signaling in oligodendrocyte lineage cells implying a role of S1P1 signaling in remyelination.


Asunto(s)
Esclerosis Múltiple , Remielinización , Ratones , Animales , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/uso terapéutico , Cuprizona , Receptores de Lisoesfingolípidos/metabolismo , Receptores de Lisoesfingolípidos/uso terapéutico , Sistema Nervioso Central/metabolismo , Esclerosis Múltiple/metabolismo , Oligodendroglía/metabolismo , beta-Arrestinas/metabolismo , beta-Arrestinas/uso terapéutico , Ratones Endogámicos C57BL
5.
Alzheimers Dement ; 19(10): 4753-4755, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37057808

RESUMEN

With the emergence of new clinical trial data on disease-modifying therapies in several. Alzheimer's disease (AD) studies, the Alzheimer's Association convened individuals living with AD to gain their perspective on meaningfulness and new treatments. A total of 30 Alzheimer's Association National Early Stage Advisory Group members participated in a focus group or an online survey to gain insights on what is wanted from a first-in-class treatment that could stop the progression of their disease at the earliest stage. Participants felt that researchers and regulators need to consider personal meaningfulness alongside clinical meaningfulness. At the same time, individuals living with AD felt that access, education, choice, and affordability were all important considerations moving forward.

6.
Alzheimers Dement ; 18(12): 2736-2746, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35917209

RESUMEN

Between 2018 and 2019, multiple clinical trials ended earlier than planned, resulting in calls to improve communication with and support for participants and their study partners ("dyads"). The multidisciplinary Participant Follow-Up Improvement in Research Studies and Trials (Participant FIRST) Work Group met throughout 2021. Its goals were to identify best practices for communicating with and supporting dyads affected by early trial stoppage. The Participant FIRST Work Group identified 17 key recommendations spanning the pre-trial, mid-trial, and post-trial periods. These focus on prospectively allocating sufficient resources for orderly closeout; developing dyad-centered communication plans; helping dyads build and maintain support networks; and, if a trial stops, informing dyads rapidly. Participants and study partners invest time, effort, and hope in their research participation. The research community should take intentional steps toward better communicating with and supporting participants when clinical trials end early. The Participant FIRST recommendations are a practical guide for embarking on that journey.


Asunto(s)
Comunicación , Humanos
7.
J Pathol ; 252(1): 29-40, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32501543

RESUMEN

The interaction of multiple myeloma (MM) cells with the bone marrow (BM) microenvironment promotes MM cell retention, survival, and resistance to different anti-MM agents, including proteasome inhibitors (PIs) such as bortezomib (BTZ). The α4ß1 integrin is a main adhesion receptor mediating MM cell-stroma interactions and MM cell survival, and its expression and function are downregulated by BTZ, leading to inhibition of cell adhesion-mediated drug resistance (CAM-DR) and MM cell apoptosis. Whether decreased α4ß1 expression and activity are maintained or recovered upon development of resistance to BTZ represents an important question, as a potential rescue of α4ß1 function could boost MM cell survival and disease progression. Using BTZ-resistant MM cells, we found that they not only rescue their α4ß1 expression, but its levels were higher than in parental cells. Increased α4ß1 expression in resistant cells correlated with enhanced α4ß1-mediated cell lodging in the BM, and with disease progression. BTZ-resistant MM cells displayed enhanced NF-κB pathway activation relative to parental counterparts, which contributed to upregulated α4 expression and to α4ß1-dependent MM cell adhesion. These data emphasize the upregulation of α4ß1 expression and function as a key event during resistance to BTZ in MM, which might indirectly contribute to stabilize this resistance, as stronger MM cell attachment to BM stroma will regain CAM-DR and MM cell growth and survival. Finally, we found a strong correlation between high ITGB1 (integrin ß1) expression in MM and poor progression-free survival (PFS) and overall survival (OS) during treatment of MM patients with BTZ and IMIDs, and combination of high ITGB1 levels and presence of the high-risk genetic factor amp1q causes low PFS and OS. These results unravel a novel prognostic value for ITGB1 in myeloma. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Integrina alfa4beta1/metabolismo , Mieloma Múltiple/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Integrina alfa4beta1/genética , Ratones , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Microambiente Tumoral
8.
Int J Equity Health ; 20(1): 110, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926471

RESUMEN

BACKGROUND: Breastfeeding can be affected by maternal employment. This is important considering that in 2019, 47.1% of women globally participated in the labor force. The aim of this study was to review workplace interventions to promote, protect and support breastfeeding practices among working mothers globally. METHODS: A systematic review was conducted following the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Observational, experimental and qualitative peer-reviewed studies in English and Spanish, published between 2008 and 2019 were included. The review focused on working women who were pregnant, breastfeeding or who recently had a child, and women's working environments. The outcomes of interest included breastfeeding intentions, initiation, exclusivity and duration, confidence in breastfeeding or breastmilk extraction, and perceived support at workplace. Quality was assessed according to National Institute for Health and Care Excellence (NICE) checklist for systematic reviews. It was registered on PROSPERO (#140624). RESULTS: Data was extracted from 28 quantitative and 9 qualitative studies. The most common interventions were designated spaces for breastfeeding or breastmilk extraction (n = 24), and the support from co-workers (n = 20). The least common interventions were providing breast pumps (n = 4) and giving mothers the flexibility to work from home (n = 3). Studies explored how interventions affected different breastfeeding outcomes including breastfeeding duration, breastfeeding exclusivity, confidence in breastmilk expression, and breastfeeding support. The evidence suggests that workplace interventions help increase the duration of breastfeeding and prevent early introduction of breastmilk substitutes. Having a lactation space, breastmilk extraction breaks, and organizational policies are key strategies. However, to achieve equitable working conditions for breastfeeding mothers, organizational and interpersonal changes need to occur as well. CONCLUSIONS: The systematic review revealed that interventions at the workplace are important in protecting, promoting and supporting breastfeeding among working mothers. To achieve equitable work environments and fair nutritional opportunities for infants of working mothers, interventions should focus at the three ecological layers - individual, interpersonal, and organizational. The quality of studies can be improved. There is a need for studies assessing impacts of workplace interventions on infant feeding practices, mothers' self-esteem and outcomes such productivity and abstentionism.


Asunto(s)
Lactancia Materna , Madres/psicología , Mujeres Trabajadoras , Lugar de Trabajo , Adolescente , Adulto , Canadá , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Encuestas Nutricionales , Embarazo , Estudios Prospectivos
9.
Int J Mol Sci ; 23(1)2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-35008872

RESUMEN

The Wnt/ß-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/ß-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/ß-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after ß-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of ß-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of ß-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/ß-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.


Asunto(s)
Resistencia a Antineoplásicos , Células Madre Neoplásicas/metabolismo , Paclitaxel/uso terapéutico , Neoplasias de la Vejiga Urinaria/metabolismo , Vía de Señalización Wnt , Línea Celular Tumoral , Humanos , Células Madre Neoplásicas/patología , Neoplasias de la Vejiga Urinaria/patología
10.
J Nurs Manag ; 29(7): 1924-1933, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33844359

RESUMEN

AIMS: To analyse the relationship between work engagement, sense of coherence and psychological distress levels in Spanish health professionals who were active during the COVID-19 pandemic lockdown. BACKGROUND: Work engagement and sense of coherence can help professionals to cope with work-related psychological distress due to the harsh conditions of the COVID-19 working environment. METHODS: Cross-sectional observational study of 1,459 health care professionals. The Utrecht Work Engagement Scale, the Sense of Coherence Scale and Goldberg's General Health Questionnaire were distributed and analysed with descriptive and multiple linear regression methods. RESULTS: High levels of work engagement, especially in the dedication dimension, of sense of coherence, in particular in the meaningfulness dimension, and psychological distress were obtained. Significant correlations (p < .001) were identified between all the variables. CONCLUSIONS: Work engagement and sense of coherence correlated positively with each other and both negatively with psychological distress. So, health care professionals, despite presenting psychological distress, perceive their work satisfactorily and positively despite the severity of the situation and the harsh conditions. IMPLICATIONS FOR NURSING MANAGEMENT: Sense of coherence and work engagement are protective factors against psychological distress. Preventive measures for professionals should go through the dimensionalization of the problem and the adaptation of practical measures for daily management.


Asunto(s)
COVID-19 , Pandemias , Control de Enfermedades Transmisibles , Estudios Transversales , Personal de Salud , Humanos , SARS-CoV-2 , España
11.
Matern Child Nutr ; 16(3): e12972, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32037674

RESUMEN

Although the isolated effects of several specific nutrients have been examined, little is known about the relationship between overall maternal diet during pregnancy and fetal development and growth. This study evaluates the association between maternal diet and low birthweight (LBW) in 660 pregnant women from the Pregnancy Research on Inflammation, Nutrition,& City Environment: Systematic Analyses (PRINCESA) cohort in Mexico City. Using prior day dietary intake reported at multiple prenatal visits, diet was assessed prospectively using a priori (Maternal Diet Quality Score [MDQS]) and a posteriori (dietary patterns extracted by factor analysis) approaches. The association between maternal diet and LBW was investigated by logistic regression, controlling for confounders. Adherence to recommended guidelines (higher MDQS) was associated with a reduced risk of LBW (OR, 0.22; 95% confidence interval [0.06, 0.75], P < .05, N = 49) compared with the lowest adherence category (reference group), controlling for maternal age, education, height, marital status, pre-pregnancy body mass index, parity, energy intake, gestational weight gain, and preterm versus term birth; a posteriori dietary patterns were not associated with LBW risk. Higher adherence to MDQS was associated with a lower risk of having an LBW baby in this sample. Our results support the role of advocating a healthy overall diet, versus individual foods or nutrients, in preventing LBW.


Asunto(s)
Dieta/métodos , Desarrollo Fetal , Recién Nacido de Bajo Peso , Fenómenos Fisiologicos Nutricionales Maternos , Política Nutricional , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , México , Embarazo , Estudios Prospectivos , Adulto Joven
12.
Appl Opt ; 58(11): 2839-2844, 2019 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-31044886

RESUMEN

In this study we report the development of a novel viral pathogen immunosensor technology based on the electrochemical modulation of the optical signal from a surface plasmon wave interacting with a redox dye reporter. The device is formed by incorporating a sandwich immunoassay onto the surface of a plasmonic device mounted in a micro-electrochemical flow cell, where it is functionalized with a monoclonal antibody aimed to a specific target pathogen antigen. Once the target antigen is bound to the surface, it promotes the capturing of a secondary polyclonal antibody that has been conjugated with a redox-active methylene blue dye. The methylene blue displays a reversible change in the complex refractive index throughout a reduction-oxidation transition, which generates an optical signal that can be electrochemically modulated and detected at high sensitivity. For proof-of-principle measurements, we have targeted the hemagglutinin protein from the H5N1 avian influenza A virus to demonstrate the capabilities of our device for detection and quantification of a critical influenza antigen. Our experimental results of the EC-SPR-based immunosensor under potential modulation showed a 300 pM limit of detection for the H5N1 antigen.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos Virales/análisis , Inmunoensayo/instrumentación , Subtipo H5N1 del Virus de la Influenza A/inmunología , Azul de Metileno/química , Resonancia por Plasmón de Superficie/instrumentación , Técnicas Biosensibles/instrumentación , Límite de Detección
13.
Blood ; 128(18): 2241-2252, 2016 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-27625360

RESUMEN

Tumor-associated macrophages (TAM) are important components of the multiple myeloma (MM) microenvironment that support malignant plasma cell survival and resistance to therapy. It has been proposed that macrophages (MØ) retain the capacity to change in response to stimuli that can restore their antitumor functions. Here, we investigated several approaches to reprogram MØ as a novel therapeutic strategy in MM. First, we found tumor-limiting and tumor-supporting capabilities for monocyte-derived M1-like MØ and M2-like MØ, respectively, when mixed with MM cells, both in vitro and in vivo. Multicolor confocal microscopy revealed that MM-associated MØ displayed a predominant M2-like phenotype in the bone marrow of MM patient samples, and a high expression of the pro-M2 cytokine macrophage migration inhibitory factor (MIF). To reprogram the protumoral M2-like MØ present in MM toward antitumoral M1-like MØ, we tested the pro-M1 cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) plus blockade of the M2 cytokines macrophage colony-stimulating factor or MIF. The combination of GM-CSF plus the MIF inhibitor 4-iodo-6-phenyl-pyrimidine achieved the best reprogramming responses toward an M1 profile, at both gene and protein expression levels, as well as remarkable tumoricidal effects. Furthermore, this combined treatment elicited MØ-dependent therapeutic responses in MM xenograft mouse models, which were linked to upregulation of M1 and reciprocal downregulation of M2 MØ markers. Our results reveal the therapeutic potential of reprogramming MØ in the context of MM.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Técnicas de Reprogramación Celular/métodos , Factores Inhibidores de la Migración de Macrófagos/antagonistas & inhibidores , Macrófagos/patología , Mieloma Múltiple/inmunología , Animales , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Microscopía Confocal , Pirimidinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Rev Med Chil ; 146(6): 727-736, 2018 Jun.
Artículo en Español | MEDLINE | ID: mdl-30148904

RESUMEN

BACKGROUND: One of the peculiarities of our society is the increase in violence and its repercussions in various areas. Health care is not an exemption. AIM: To determine the prevalence of physical violence, verbal abuse towards emergency service health care workers at two public and two private health centers in the province of Concepción, Chile. MATERIAL AND METHODS: A questionnaire for Work Violence in Health Centers, with dimensions about physical violence and verbal abuse was applied to 366 health care workers, stratified according to center and occupational categories. RESULTS: Thirteen percent of workers perceived physical violence. Paramedical technicians had the higher risk of perceiving this type of violence. Fifty nine percent of workers perceived verbal abuse. Nurses and administrative staff had the higher risk of perceiving this type of violence. The most common offenders were patients and family. The most common form of coping with abuse was avoiding a reaction. Most of the physical and verbal aggressions were not reported or denounced. CONCLUSIONS: There is a high prevalence of verbal abuse and physical violence in emergency services, which requires measures to achieve a zero tolerance to violence in these spaces.


Asunto(s)
Agresión , Servicios Médicos de Urgencia/estadística & datos numéricos , Exposición a la Violencia/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Abuso Físico/estadística & datos numéricos , Violencia Laboral/estadística & datos numéricos , Adulto , Chile , Estudios Transversales , Femenino , Instituciones de Salud/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Exposición Profesional/estadística & datos numéricos , Sector Privado , Sector Público , Encuestas y Cuestionarios , Carga de Trabajo , Adulto Joven
15.
Opt Lett ; 42(7): 1205-1208, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28362730

RESUMEN

Here we report the development of a novel immunosensor-based strategy for label-free detection of viral pathogens by incorporating a sandwich bioassay onto a single-mode, electro-active, integrated optical waveguide (EA-IOW). Our strategy begins with the functionalization of the electro-active waveguide surface with a capture antibody aimed at a specific virus antigen. Once the target antigen is bound to the photonic interface, it promotes the binding of a secondary antibody that has been labeled with a methylene blue (MB) dye. The MB is a redox-active probe whose optical absorption can be electrically modulated and interrogated with high sensitivity by a propagating waveguide mode. In this effort, we have targeted the hemagglutinin (HA) protein from the H5N1 avian influenza A virus to demonstrate the capabilities of the EA-IOW device for detection and quantification of an important antigen. Our initial results for the HA H5N1 influenza virus show a remarkable limit of detection in the pico-molar range.


Asunto(s)
Técnicas Biosensibles/instrumentación , Electricidad , Inmunoensayo/instrumentación , Subtipo H5N1 del Virus de la Influenza A/inmunología , Dispositivos Ópticos , Glicoproteínas Hemaglutininas del Virus de la Influenza/análisis , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Límite de Detección
16.
J Neurosci ; 34(24): 8175-85, 2014 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-24920622

RESUMEN

Current multiple sclerosis (MS) therapies only partially prevent chronically worsening neurological deficits, which are largely attributable to progressive loss of CNS axons. Prior studies of experimental autoimmune encephalomyelitis (EAE) induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide), a model of MS, documented continued axon loss for months after acute CNS inflammatory infiltrates had subsided, and massive astroglial induction of CCL2 (MCP-1), a chemokine for CCR2(+) monocytes. We now report that conditional deletion of astroglial CCL2 significantly decreases CNS accumulation of classically activated (M1) monocyte-derived macrophages and microglial expression of M1 markers during the initial CNS inflammatory phase of MOG peptide EAE, reduces the acute and long-term severity of clinical deficits and slows the progression of spinal cord axon loss. In addition, lack of astroglial-derived CCL2 results in increased accumulation of Th17 cells within the CNS in these mice, but also in greater confinement of CD4(+) lymphocytes to CNS perivascular spaces. These findings suggest that therapies designed to inhibit astroglial CCL2-driven trafficking of monocyte-derived macrophages to the CNS during acute MS exacerbations have the potential to significantly reduce CNS axon loss and slow progression of neurological deficits.


Asunto(s)
Astrocitos/metabolismo , Axones/patología , Sistema Nervioso Central/patología , Quimiocina CCL2/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Macrófagos/metabolismo , Análisis de Varianza , Animales , Axones/ultraestructura , Proteínas Bacterianas/genética , Sistema Nervioso Central/ultraestructura , Quimiocina CCL2/genética , Citometría de Flujo , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas Luminiscentes/genética , Macrófagos/inmunología , Macrófagos/ultraestructura , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Glicoproteína Mielina-Oligodendrócito/toxicidad , Fragmentos de Péptidos/toxicidad , Proteínas/genética
17.
Electrophoresis ; 36(16): 1945-52, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26033384

RESUMEN

This work reports on the positive effects observed upon both the separation and analytical signals in electrophoretic separations of selected phenolic compounds when using aqueous BGE containing carbon nanotubes (CNTs) in connection to electrochemical detection (ECD). The influence of the presence of surfactant-coated CNTs in the BGE upon the amperometric response of probe compounds was evaluated under hydrodynamic regime in capillary flow injection experiments as well as electrophoretic separations. Among the surfactants employed to disperse CNTs within BGE, SDS shows the best results in terms of dispersion stability and degree of dispersion of the CNTs. ECD allows working with BGEs containing CNTs concentrations of, at least, 24.0 mg/L without increasing of baseline noise, on the opposite to that reported when using UV-visible detection, and the presence of CNTs in the BGE improves the electrochemical response of some of the tested compounds. These benefits were reflected in higher sensibility in the electrochemical signal and additional improved resolution in the electrophoretic separation of (±)-catechin and sinapic acid when using these BGE containing CNTs.


Asunto(s)
Cromatografía Capilar Electrocinética Micelar/métodos , Nanotubos de Carbono/química , Fenoles/análisis , Ácido 3,4-Dihidroxifenilacético/análisis , Dopamina/análisis , Electrólitos , Modelos Lineales , Fenoles/química , Fenoles/aislamiento & purificación
18.
Electrophoresis ; 35(11): 1693-700, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24585496

RESUMEN

A method was developed for the simultaneous detection of eight polyphenols (t-resveratrol, (+)-catechin, quercetin and p-coumaric, caffeic, sinapic, ferulic, and gallic acids) by CZE with electrochemical detection. Separation of these polyphenols was achieved within 25 min using a 200 mM borate buffer (pH 9.4) containing 10% methanol as separation electrolyte. Amperometric detection of polyphenols was carried out with a glassy carbon electrode (GCE) modified with a multiwalled carbon nanotubes (CNT) layer obtained from a dispersion of CNT in polyethylenimine. The excellent electrochemical properties of this modified electrode allowed the detection and quantification of the selected polyphenols in white wines without any pretreatment step, showing remarkable signal stability despite the presence of potential fouling substances in wine. The electrophoretic profiles of white wines, obtained using this methodology, have proven to be useful for the classification of these wines by means of chemometric multivariate techniques. Principal component analysis and discriminant analysis allowed accurate classification of wine samples on the basis of their grape varietal (verdejo and airén) using the information contained in selected zones of the electropherogram. The utility of the proposed CZE methodology based on the electrochemical response of CNT-modified electrodes appears to be promising in the field of wine industry and it is expected to be successfully extended to classification of a wider range of wines made of other grape varietals.


Asunto(s)
Electroforesis Capilar/métodos , Polifenoles/análisis , Vino/análisis , Vino/clasificación , Electrodos , Electroforesis Capilar/instrumentación , Nanotubos de Carbono/química , España
19.
Sensors (Basel) ; 14(2): 3408-27, 2014 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-24556674

RESUMEN

Partial discharge (PD) detection is a standardized technique to qualify electrical insulation in machines and power cables. Several techniques that analyze the waveform of the pulses have been proposed to discriminate noise from PD activity. Among them, spectral power ratio representation shows great flexibility in the separation of the sources of PD. Mapping spectral power ratios in two-dimensional plots leads to clusters of points which group pulses with similar characteristics. The position in the map depends on the nature of the partial discharge, the setup and the frequency response of the sensors. If these clusters are clearly separated, the subsequent task of identifying the source of the discharge is straightforward so the distance between clusters can be a figure of merit to suggest the best option for PD recognition. In this paper, two inductive sensors with different frequency responses to pulsed signals, a high frequency current transformer and an inductive loop sensor, are analyzed to test their performance in detecting and separating the sources of partial discharges.

20.
Alzheimers Dement (Amst) ; 16(1): e12530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38496717

RESUMEN

Alzheimer's disease (AD) is the most common cause of dementia, a general term for memory loss and decline in other cognitive abilities enough to interfere with daily life. AD accounts for 60% to 80% of dementia cases. The late stage of AD tends to be the shortest stage and, on average, lasts 1 to 2 years. As this stage of the condition progresses, it requires continuous intensive long-term care and around-the-clock intensive care. The Alzheimer's Association stands firm in its commitment to supporting individuals living with AD and other dementia, their care partners, and their health-care providers as they navigate treatment and care decisions across the continuum of the disease. This article is a direct response to recently published works that run counter to the Association's viewpoint. It outlines the Association's perspective on crucial factors for consideration during late-stage dementia care, including advanced directives, palliative care, nutrition, and legal considerations. It explores diverse perspectives from the field, differing from the Alzheimer's Association's stance. Last, it underscores resources available through the Alzheimer's Association, aiming to present a comprehensive perspective on late-stage care for support and assistance to all involved.

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