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OBJECTIVES: We aimed to evaluate the epidemiology of seven infections (Chagas disease, strongyloidiasis, schistosomiasis, human immunodeficiency virus, hepatitis B and C virus, and active tuberculosis) in migrant populations attended at primary care facilities in Catalonia, Spain. METHODS: This is a cross sectional study conducted from March to December 2018 at eight primary care centres in Catalonia, Spain where health professionals were recommended to systematically screen multiple infections in migrants considering the endemicity of the pathogens in their country of birth. Routine health data were retrospectively extracted from electronic health records of the primary care centres. The proportion of cases among individuals tested for each infection was estimated with its 95% confident interval (CI). Mixed-effects logistics regression models were conducted to assess any possible association between the exposure variables and the primary outcome. RESULTS: Out of the 15,780 migrants that attended primary care centres, 2410 individuals were tested for at least one infection. Of the 508 (21.1%) migrants diagnosed with at least one condition, a higher proportion originated from Sub-Saharan Africa (207, 40.7%), followed by South-East Europe (117, 23.0%) and Latin-America (88, 17.3%; p value <0.001). The proportion of migrants diagnosed with Chagas disease was 5/122 (4.1%, 95%CI 0.5-7.7), for strongyloidiasis 56/409 (13.7%, 95%CI 10.3-17.0) and for schistosomiasis 2/101 (2.0%, 95%CI 0.0-4.7) with very few cases tested. The estimated proportion for human immunodeficiency virus was 67/1176 (5.7%, 95%CI 4.4-7.0); 377/1478 (25.5%, 95%CI 23.3-27.7) for hepatitis B virus, with 108/1478 (7.3%, 95%CI 6.0-8.6) of them presenting an active infection, while 31/1433 (2.2%, 95%CI 1.4-2.9) were diagnosed with hepatitis C virus. One case of active tuberculosis was diagnosed after testing 172 migrant patients (0.6%, 95%CI 0.0-1.7). CONCLUSIONS: We estimated a high proportion of the studied infections in migrants from endemic areas. Country-specific estimations of the burden of infections in migrants are fundamental for the implementation of preventive interventions.
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BACKGROUND AND PURPOSE: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. EXPERIMENTAL APPROACH: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARß/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-κB activation. PPARs/RXRα interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. KEY RESULTS: BP-2 displayed strong PPARα activity, with moderate and weak activity against PPARß/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARß/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. CONCLUSION AND IMPLICATIONS: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.
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Enfermedades Metabólicas , PPAR delta , PPAR-beta , Ratones , Animales , PPAR gamma/metabolismo , PPAR alfa/metabolismo , PPAR-beta/metabolismo , Factor de Necrosis Tumoral alfa , Benzopiranos , FN-kappa B , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológicoRESUMEN
2-Prenylated benzopyrans represent a class of natural and synthetic compounds showing a wide range of significant activities. Polycerasoidol is a natural prenylated benzopyran isolated from the stem bark of Polyalthia cerasoides (Annonaceae) that exhibits dual PPARα/γ agonism and an anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium. Herein, we report the synthesis of three new series of prenylated benzopyrans containing one (series 1), two (series 2, "polycerasoidol" analogs) and three (series 3, "trans-δ-tocotrienolic acid" analogs) isoprenoid units in the hydrocarbon side chain at the 2-position of the chroman-6-ol (6-hydroxy-dihydrobenzopyran) scaffold. Isoprenoid moieties were introduced through a Grignard reaction sequence, followed by Johnson-Claisen rearrangement and subsequent Wittig olefination. hPPAR transactivation activity and the structure activity relationships (SAR) of eleven novel synthesized 2-prenylated benzopyrans were explored. PPAR transactivation activity demonstrated that the seven-carbon side chain analogs (series 1) displayed selectivity for hPPARα, while the nine-carbon side chain analogs (polycerasoidol analogs, series 2) did so for hPPARγ. The side chain elongation to 11 or 13 carbons (series 3) resulted in weak dual PPARα/γ activation. Therefore, 2-prenylated benzopyrans of seven- and nine-carbon side chain (polycerasoidol analogs) are good lead compounds for developing useful candidates to prevent cardiovascular diseases associated with metabolic disorders.
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Antiinflamatorios no Esteroideos/farmacología , Benzopiranos/farmacología , PPAR alfa/agonistas , PPAR gamma/agonistas , Vitamina E/análogos & derivados , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Benzopiranos/síntesis química , Benzopiranos/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Relación Estructura-Actividad , Vitamina E/síntesis química , Vitamina E/química , Vitamina E/farmacologíaRESUMEN
Certain D2-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D2-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzyl)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline (Br-BTHIQ, 1) and 1,2-demethyl-nuciferine (aporphine, 2), were herein synthesized, and their dopaminergic affinity in cloned human D2R, D3R, and D4R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (Ki) for hD2, hD3, and hD4 DR within the nanomolar range. The trends in affinity were hD4R â« hD3R > hD2R for Br-BTHIQ (1) and hD2R > hD4R > hD3R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D2R showed a partial agonist effect for Br-BTHIQ (1) and full agonist behavior for aporphine (2), with half maximal effective concentration values of 2.95 and 10.2 µM, respectively. Therefore, both isoquinolines 1 and 2 have emerged as lead molecules for the synthesis of new therapeutic drugs that ultimately may be useful to prevent schizophrenia and Parkinson's disease, respectively.
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Aporfinas/química , AMP Cíclico/química , Agonistas de Dopamina/química , Tetrahidroisoquinolinas/farmacología , Animales , Aporfinas/farmacología , Humanos , Isoquinolinas/química , Estructura Molecular , Tetrahidroisoquinolinas/químicaRESUMEN
We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski's rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head ("carboxylic group") tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes.
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Benzopiranos/síntesis química , Benzopiranos/farmacología , PPAR alfa/agonistas , PPAR gamma/agonistas , Benzopiranos/química , Descubrimiento de Drogas , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7-bromo-2-(2-phenylethyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti-inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil-endothelial cell interactions. The information obtained from our theoretical and experimental study can be useful in the search for inhibitors of SphK2 that play a prominent role in different diseases, especially in inflammatory and cardiovascular disorders.
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Antiinflamatorios/síntesis química , Azepinas/síntesis química , Inhibidores Enzimáticos/síntesis química , Compuestos Epoxi/síntesis química , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/toxicidad , Azepinas/química , Azepinas/farmacología , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/toxicidad , Compuestos Epoxi/química , Compuestos Epoxi/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Simulación del Acoplamiento Molecular , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Unión Proteica , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To determine the prevalence and profiles of people with advanced chronic diseases in Primary Care and to analyse the elements related to their mortality in order to orient strategies for improvement in this level of care. DESIGN: An observational, analytical and prospective study during 3 years conducted on a cohort of patients with palliative needs. LOCATION: Three Primary Care teams of Osona (Catalonia). PARTICIPANTS: A total of 251 people identified as advanced patients using a systematic population-based strategy that included the NECPAL tool. MAIN MEASUREMENTS: Basic demographic and clinical profile (age, gender, type of residence, health stratification level and main disease); date, place, and cause of eventual deaths. RESULTS: 1% of the adult Primary Care population suffer from advanced diseases, of which 56.6% are women, and with a median age of 85 years. Dementia or advanced frailty is observed in 49.3%, and only 13.7% have cancer. Just under one-quarter (24.3%) live in nursing homes. The accumulated mortality at 3 years is 62.1%, with a median survival of 23 months. Factors significantly associated with the likelihood of dying are cancer, female gender, and over-aging. Patients died at their home (47.3%), in an intermediate care hospital (37.2%), or in an acute care hospital (15.5%), depending on certain explanatory factors. CONCLUSIONS: The prevalence and characteristics of advanced community-based disease coincide with that reported in the literature. Potentially, Primary Care is the reference level of care for these patients, especially if it incorporates nursing homes as a usual field of practice.
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Enfermedad Crónica/epidemiología , Cuidados Paliativos , Atención Primaria de Salud , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Prevalencia , Estudios Prospectivos , Índice de Severidad de la Enfermedad , España/epidemiología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The biological effects of nanoparticles depend on several characteristics such as size and shape that must be taken into account in any type of assessment. The increased use of titanium dioxide nanoparticles (TiO2NPs) for industrial applications, and specifically as a food additive, demands a deep assessment of their potential risk for humans, including their abilities to cross biological barriers. METHODS: We have investigated the interaction of three differently shaped TiO2NPs (nanospheres, nanorods and nanowires) in an in vitro model of the intestinal barrier, where the coculture of Caco-2/HT29 cells confers inherent intestinal epithelium characteristics to the model (i.e. mucus secretion, brush border, tight junctions, etc.). RESULTS: Adverse effects in the intestinal epithelium were detected by studying the barrier's integrity (TEER), permeability (LY) and changes in the gene expression of selected specific markers. Using Laser Scanning Confocal Microscopy, we detected a different behaviour in the bio-adhesion and biodistribution of each of the TiO2NPs. Moreover, we were able to specifically localize each type of TiO2NPs inside the cells. Interestingly, general DNA damage, but not oxidative DNA damage effects, were detected by using the FPG version of the comet assay. CONCLUSIONS: Results indicate different interactions and cellular responses related to differently shaped TiO2NPs, nanowires showing the most harmful effects.
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Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Nanosferas/toxicidad , Nanotubos/toxicidad , Nanocables/toxicidad , Titanio/toxicidad , Células CACO-2 , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Nanosferas/química , Nanotubos/química , Nanocables/química , Tamaño de la Partícula , Permeabilidad , Propiedades de Superficie , Titanio/química , Titanio/farmacocinéticaRESUMEN
The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in commercial food products makes intestinal cells a suitable target. Accordingly, we have used the human colon adenocarcinoma Caco-2 cells to detect their potential harmful effects. Caco-2 cells can differentiate in to enterocytic-like cells, forming consistent cell monolayers and are used as a model of the intestinal barrier. Using both undifferentiated and differentiated Caco-2 cells, we have explored a set of biomarkers, aiming to evaluate undesirable effects associated to TiO2 NP exposure. Results indicate non-toxic effects in exposures ranging 1-200 µg ml-1 . Significant differences were observed in cell uptake, with a higher amount of incorporated TiO2 NPs in undifferentiated cells, as visualized using confocal microscopy. In well-established monolayers, translocation was detected using both confocal microscopy and transmission electron microscopy with energy-dispersive X-ray spectroscopy. In spite of the observed uptake and translocation, TiO2 NP exposures did not modify the integrity of the monolayer, as measured using the transepithelial electrical resistance and Lucifer yellow methods. The potential genotoxic effects in differentiated cells were evaluated in the comet assay, with and without formamidopyrimidine DNA glycosylase enzyme to detect oxidatively the damaged DNA bases. Although some changes were detected at the lower dose (10 µg ml-1 ), no effects were observed at higher doses.
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Absorción Intestinal , Mucosa Intestinal/metabolismo , Nanopartículas del Metal , Titanio/metabolismo , Transporte Biológico , Células CACO-2 , Diferenciación Celular , Daño del ADN , Relación Dosis-Respuesta a Droga , Impedancia Eléctrica , Humanos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/ultraestructura , Nanopartículas del Metal/toxicidad , Estrés Oxidativo , Permeabilidad , Medición de Riesgo , Titanio/toxicidadRESUMEN
OBJECTIVES: 1-To know the preventive prescription (statin, antiplatelet drugs, bisphosphonates, calcium and vitamin D and Vit B12) of elderly patients previously identified as a CCD (with a complex chronic disease) and ACD (with advanced chronic disease and lifetime expectancy of less than 12 months) who died during 2015. 2-To assess the correct indication of Proton Pump Inhibitors (PPI) to determine potentially avoidable medication. DESIGN: Retrospective observational study. LOCATION: Four Primary Health Centres, Castellar del Vallès (Barcelona). PARTICIPANTS: 128 patients, 70 ACD and 58 PCC. MAIN MEASUREMENTS: Number of drugs at the time of death from the 6 selected group, deprescription (6 months prior to death due to advanced chronic disease), primary or secondary prevention and inappropriate prescription of PPI. RESULTS: Average age of 85'3 years (10,3). 40% took an antiplatelet drug, avoidable in 60% of the ACD, since they did not present any previous cardiovascular episode. 20% of the patients took statins, in which 48% of the cases were primary prevention. The PPI prescription was 67% with inadequate indication for use in 49% of these cases. 20% took calcium / Vitamin D and 1,6% of the ACD a bisphosphonate. There was a 16% deprescription. CONCLUSIONS: A high percentage of our patients with advanced chronic disease and short life expectancy still continue to take preventive and avoidable treatments, potentially dangerous due to their side effects. There is a need to reflect on what we do with these vulnerable patients.
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Enfermedad Crónica , Deprescripciones , Medicamentos bajo Prescripción/uso terapéutico , Prevención Primaria , Prevención Secundaria , Anciano de 80 o más Años , Estudios Transversales , Humanos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The Surprise Question (SQ) identifies patients with palliative care needs. The NECPAL CCOMS-ICO© (NECPAL) tool combines the Surprise Question with additional clinical parameters for a more comprehensive assessment. The capacity of these screening tools to predict mortality is still unknown. AIM: To explore the predictive validity of the NECPAL and SQ to determine 12- to 24-month mortality. DESIGN: Longitudinal, prospective and observational cohort study. SETTING/PARTICIPANTS: Three primary care centres, one general hospital, one intermediate care centre, and four nursing homes. Population cohort with advanced chronic conditions and limited life prognosis. Patients were classified according to SQ and NECPAL criteria and followed for 24 months. RESULTS: Data available to assess 1059 of 1064 recruited patients (99.6%) at 12 and 24 months: 837 patients were SQ+ and 780 were NECPAL+. Mortality rates at 24 months were as follows: 44.6% (SQ+) versus 15.8% (SQ-) and 45.8% (NECPAL+) versus 18.3% (NECPAL-) ( p = 0.000). SQ+ and NECPAL+ identification was significantly correlated with 24-month mortality risk (hazard ratios: 2.719 and 2.398, respectively). Both tools were highly sensitive (91.4, CI: 88.7-94.1 and 87.5, CI: 84.3-90.7) with high negative predictive values (84.2, CI: 79.4-89.0 and 81.7, CI: 77.2-86.2), with low specificity and positive predictive value. The prognostic accuracy of SQ and NECPAL was 52.9% and 55.2%, respectively. The predictive validity was slightly better for NECPAL. CONCLUSION: SQ and NECPAL are valuable screening instruments to identify patients with limited life prognosis who may require palliative care. More research is needed to increase its prognostic utility in combination with other parameters.
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Enfermedad Crónica/terapia , Cuidados Paliativos , Encuestas y Cuestionarios/normas , Anciano , Enfermedad Crónica/mortalidad , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Masculino , Planificación de Atención al Paciente , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo/métodosRESUMEN
Cerium oxide nanoparticles (CeO2-NP) present two different oxidation states what can suppose an auto-regenerative redox cycle. Potential applications of CeO2-NP to quench reactive oxygen species (ROS) in biological systems are currently being investigated. In this context, CeO2-NP may represent a novel agent to protect cells and tissues against oxidative damage by its regenerative free radical-scavenging properties. In this study, we have used a human epithelial lung cell line, BEAS-2B, as a model to study the possible antioxidant and anti-genotoxic effect of CeO2-NP in a pulmonary-like system. We have assessed the protective effect of CeO2-NP pre-treatment in front of a well-defined oxidative stress-inducing agent (KBrO3). Different endpoints like toxicity, intracellular ROS induction, genotoxicity and DNA oxidative damage (comet assay), and gene expression alterations have been evaluated. The obtained results confirmed the antioxidant properties of CeO2-NP. Thus, its pre-treatment significantly reduced the intracellular production of ROS induced by KBrO3. Similarly, a reduction in the levels of DNA oxidative damage, as measured with the comet assay complemented with formamidopyrimidine DNA glycosylase enzyme, was also observed. Pre-treatment of BEAS-2B cells with CeO2-NP (at 2.5 µg/mL) slightly increased the viability of cells treated with KBrO3 as well as down-regulated the expression of the Ho1 and Sod2 genes involved in the oxidative Nrf2 pathway. Our finding would support the potential usefulness of CeO2-NP as a pharmacological agent to be used against diseases caused by oxidative stress.
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Antioxidantes/farmacología , Bronquios/citología , Cerio/farmacología , Antimutagênicos/farmacología , Bromatos/farmacología , Bromatos/toxicidad , Línea Celular , Cerio/química , Ensayo Cometa , Regulación de la Expresión Génica/efectos de los fármacos , Gutatión-S-Transferasa pi/genética , Humanos , Nanopartículas del Metal/química , Microscopía Electrónica de Transmisión , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genéticaAsunto(s)
COVID-19/prevención & control , Seguridad del Paciente/normas , Atención Primaria de Salud/métodos , Telemedicina/normas , Teléfono , Humanos , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud/organización & administración , Telemedicina/métodos , Telemedicina/organización & administraciónRESUMEN
AIM: To understand the experiences of patients and caregivers living with advanced chronic obstructive pulmonary disease, the impact of their symptoms and care needs arising from a functional, emotional, and social context. DESIGN: Qualitative study. Phenomenological perspective. Data were collected during 2013-2015. SETTING: Primary, secondary and intermediate care. Osona (Barcelona). PARTICIPANTS: The study included 10 Primary Care patients with advanced chronic obstructive pulmonary disease, their respective 10 caregivers, and 19 primary care professionals, as well as 2 lung specialists, 2 palliative care professionals involved in their care, and one clinical psychologist. METHOD: Theoretical sampling. Semi-structured and in-depth interviews with patients, caregivers, and professionals (47 interviews). RESULTS: The emergent topics identified in patients and caregivers interviews refer to dyspnoea, the predominant symptom without effective treatment and with a major impact on patients and caregivers lives. A symptom with great functional, emotional and social repercussions to which they need to adapt in order to survive. CONCLUSIONS: Beyond pharmacological measures to control respiratory symptoms, proper care of patients with chronic obstructive pulmonary disease, requires understanding of suffering, the losses and limitations that it causes in their lives and those of their caregivers. A palliative, holistic and closer approach to their real experiences, together with an empowerment to adapt to debilitating symptoms, could contribute to a better life in the end-stages of the disease.
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Actitud Frente a la Salud , Cuidadores , Disnea/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Anciano de 80 o más Años , Cuidadores/psicología , Salud de la Familia , Femenino , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/terapia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Of deaths in high-income countries, 75% are caused by progressive advanced chronic conditions. Palliative care needs to be extended from terminal cancer to these patients. However, direct measurement of the prevalence of people in need of palliative care in the population has not been attempted. AIM: Determine, by direct measurement, the prevalence of people in need of palliative care among advanced chronically ill patients in a whole geographic population. DESIGN: Cross-sectional, population-based study. MAIN OUTCOME MEASURE: prevalence of advanced chronically ill patients in need of palliative care according to the NECPAL CCOMS-ICO(©) tool. NECPAL+ patients were considered as in need of palliative care. SETTING/PARTICIPANTS: County of Osona, Catalonia, Spain (156,807 inhabitants, 21.4% > 65 years). Three randomly selected primary care centres (51,595 inhabitants, 32.9% of County's population) and one district general hospital, one social-health centre and four nursing homes serving the patients. Subjects were all patients attending participating settings between November 2010 and October 2011. RESULTS: A total of 785 patients (1.5% of study population) were NECPAL+: mean age = 81.4 years; 61.4% female. Main disease/condition: 31.3% advanced frailty, 23.4% dementia, 12.9% cancer (ratio of cancer/non-cancer = 1/7), 66.8% living at home and 19.7% in nursing home; only 15.5% previously identified as requiring palliative care; general clinical indicators of severity and progression present in 94% of cases. CONCLUSIONS: Direct measurement of prevalence of palliative care needs on a population basis is feasible. Early identification and prevalence determination of these patients is likely to be the cornerstone of palliative care public health policies.
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Enfermedad Crónica/epidemiología , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Cuidados Paliativos/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , España/epidemiologíaRESUMEN
Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry. In an attempt to discover novel and safety PPAR activators, we efficiently prepared benzopyran hydrazone/hydrazine derivatives containing benzothiazole (series 1) or 5-chloro-3-(trifluoromethyl)-2-pyridine moiety (series 2) with a 3- or 7-carbon side chain at the 2-position of the benzopyran nucleus. Benzopyran hydrazones 4 and 5 showed dual hPPARα/γ agonism, while hydrazone 14 exerted dual hPPARα/δ agonism. These three hydrazones greatly attenuated inflammatory markers such as IL-6 and MCP-1 on the THP-1 macrophages via NF-κB activation. Therefore, we have discovered novel hits (4, 5 and 14), containing a hydrazone framework with dual PPARα/γ or PPARα/δ partial agonism, depending on the length of the side chain. Benzopyran hydrazones emerge as potential lead compounds which could be useful for treating metabolic diseases.
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Benzopiranos , PPAR alfa , Humanos , PPAR alfa/agonistas , Benzopiranos/química , Hidrazonas/farmacología , Hipoglucemiantes , PPAR gamma/agonistas , AntiinflamatoriosRESUMEN
Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: N-methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure-activity relationship showed the importance of the presence of an amine group and a p-fluorobenzyloxy substituent in the chromanol ring (IC50 values from 1.5 µM to 58.4 µM). In addition, 5a, 5b, 6a, and 7b displayed slight selectivity towards tumor cells. Compounds 5, 5a, 5b, 6, 6a, 6c, 7, and 7b showed apoptotic/necrotic effects due to, at least in part, an increase in reactive oxygen species generation, whereas 5b, 5c, 6b, 7a, and 7c caused cell cycle arrest in the G1 phase. Further cell-based mechanistic studies revealed that 5a, 6a, and 7b, which were the most promising compounds, downregulated the expression of Bcl-2, while 5b downregulated the expression of cyclins CCND1 and CCND2. Therefore, 2-aminopropyl benzopyran derivatives emerge as new hits and potential leads for developing useful agents against breast cancer.
RESUMEN
Background: Migrants in host countries are at risk for the development of mental health conditions. The two aims of the study were to describe routine diagnoses of mental disorders among migrant patients at primary healthcare level and the associated risk factors, and to test the utility of an innovative migrant mental health assessment by evaluating whether the health professionals followed the recommendations proposed by the clinical decision support system (CDSS) tool. Methods: A cross-sectional study was carried out in eight primary care centres (PCCs) in four non-randomly selected health regions of Catalonia, Spain from March to December 2018. Routine health data and mental health diagnoses based on the International Classification of Diseases (10th edition), including mental, behavioural and neuro developmental disorders (F01-F99), symptoms and signs involving emotional state (R45), and sleep disorders (G47), were extracted from the electronic health records. The proportion of mental health conditions was estimated and logistic regression models were used to assess any possible association with mental health disorders. The utility of the mental health assessment was assessed with the proportion of questionnaires performed by health professionals for migrants fulfilling the mental health screening criterion (country of origin with an active conflict in 2017) and the diagnoses given to the screened patients. Results: Of 14,130 migrants that visited any of the PCCs during the study period, 7,358 (52.1 %) were women with a median age of 38.0 years-old. There were 520/14,130 (3.7 %) migrant patients diagnosed with a mental disorder, being more frequent among women (342/7,358; 4.7 %, p-value < 0.001), migrants from Latin-America (177/3,483; 5.1 %, p < 0.001) and those who recently arrived in Spain (170/3,672; 4.6 %, p < 0.001). A lower proportion of mental disorders were reported in migrants coming from conflicted countries in 2017 (116/3,669, 3.2 %, p = 0.053).Out of the 547 mental health diagnoses reported in 520 patients, 69/14,130 (0.5 %) were mood disorders, 346/14,130 (2.5 %) anxiety disorders and 127/14,130 (0.9 %) sleeping disorders. Mood disorders were more common in migrants from Eastern Europe (25/2,971; 0.8 %, p < 0.001) and anxiety disorders in migrants from Latin-America (126/3,483; 3.6 %, p < 0.001), while both type of disorders were more often reported in women (p < 0.001).In the adjusted model, women (aOR: 1.5, [95 % CI 1.2-1.8, p < 0.001]), migrants with more than one visit to the health center during the study period (aOR: 4.4, [95 %CI 2.8-6.8, p < 0.001]) and who presented an infectious disease (aOR: 2.1, [95 %CI 1.5-3.1, p < 0.001]) had higher odds of having a mental disorder.Lastly, out of the 1,840 migrants coming from a conflicted country in 2017 who were attended in centres where the CDSS tool was implemented, 29 (1.6 %) had a mental health assessment performed and the tool correctly identified one individual. Conclusions: Mental health is a condition that may be overlooked in migrants at primary healthcare. Interventions at this level of care must be reinforced and adapted to the needs and circumstances of migrants to ensure equity in health services.
RESUMEN
Sphingosine-1-phosphate (S1P) is an immunomodulatory lipid mediator that plays an important role in lymphocyte trafficking. Elevated levels of S1P are found in bronchoalveolar lavage (BAL) fluid of patients with asthma; however, its role in disease is not known. FTY720, a synthetic analog of S1P, has been shown to abrogate allergic inflammation and airway hyperresponsiveness following acute allergen challenge. However, its effects on asthmatic airway remodeling induced by repeated allergen exposure are unknown. Ovalbumin (OVA)-sensitized rats were challenged on days 14, 19, and 24 after sensitization. FTY720 or vehicle (PBS) therapy was administered 1 h prior to each challenge. BAL fluid and quantitative histological analysis were performed 48 h after the last challenge. FTY720 inhibited OVA-induced features of airway remodeling including increased airway smooth muscle mass and bronchial neovascularization, without affecting lymphocyte numbers in secondary lymphoid organs. Furthermore, CD3+ cells adjacent to airway smooth muscle bundles were increased in OVA-challenged rats but the increase was inhibited by FTY720. There was an expansion of bronchus-associated lymphoid tissue following FTY720 treatment of OVA-challenged animals. Real-time quantitative PCR revealed that Th2-associated transcription factors were inhibited following FTY720 therapy. Airway remodeling is a cardinal feature of severe asthma. These results demonstrate that allergen-driven airway remodeling can be inhibited by FTY720, offering potential new therapies for the treatment of severe asthma.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Alérgenos/efectos adversos , Inmunosupresores/uso terapéutico , Lisofosfolípidos/agonistas , Lisofosfolípidos/uso terapéutico , Glicoles de Propileno/uso terapéutico , Esfingosina/análogos & derivados , Animales , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Bronquios/irrigación sanguínea , Bronquios/efectos de los fármacos , Bronquios/patología , Líquido del Lavado Bronquioalveolar , Complejo CD3/análisis , Clorhidrato de Fingolimod , Masculino , Músculo Liso/efectos de los fármacos , Ratas , Índice de Severidad de la Enfermedad , Esfingosina/agonistas , Esfingosina/uso terapéutico , Resultado del TratamientoRESUMEN
During the period from March 2020 to January 2021, we performed an analysis of incidence, mortality, and risk factors of COVID-19 in nursing homes (NHs) in two health departments (HDs) of Castellon (Spain) 2021 through epidemiological surveillance and an ecological design. Laboratory-confirmed COVID-19 cases, cumulative incidence rate (CIR), and mortality rate (MR) of 27 NHs were collected. Information of residents, staff, and facilities was obtained by questionnaire. Multilevel Poisson regression models were applied. All NHs in the HDs participated with 2229 residents (median: 83 years old, 67.3% women) and 1666 staff. Among residents, 815 cases (CIR: 34.8 per 100) and 202 deaths (MR: 8.7 per 100, case fatality 21.0%) were reported and, among staff, 296 cases (CIR: 19.2 per 100) without deaths. Residents' CIR and MR increased with staff CIR, age of the building, residents/staff ratios, occupancy rate, and crowding index; CIR increased with private NH ownership, large NH size, large urban area, and the percentage of women residents; and MR was associated with residents' severe disabilities. In conclusion, several risk factors of COVID-19 incidence and mortality can be prevented by improving infection and quality controls, ameliorating residents/staff ratios, improving structural facilities, and increasing NH public ownership to avoid new outbreaks.