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1.
Gynecol Endocrinol ; 40(1): 2329714, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38499020

RESUMEN

OBJECTIVE: To explore the association between anxiety and frailty in community-dwelling postmenopausal women. METHODS: This was a cross-sectional study in which 390 postmenopausal women (aged 60-83 years) who were attending a comprehensive care program were surveyed between January 2018 and February 2020. Each participant was administered a validated Spanish version of the Hospital Anxiety and Depression Scale (HADS) to assess their anxiety status. Those scoring 8 or higher on the anxiety subscale of the HADS were indicative of anxiety. The assessment of frailty utilized the Fried's phenotype, with a diagnosis of frailty established if the participant met at least three out of the five criteria. Factors associated with frailty were analyzed using multivariate logistic regression. RESULTS: The mean age of participants was 70.08 years, with an average of 12.58 ± 3.19 years since menopause. Frailty was diagnosed in 43.85% of the total series, while anxiety was present in 41.08%, rising to 69.59% in participants with frailty. Neither body mass index, years since menopause, educational level, economic status, nor smoking habit demonstrated significant associations with frailty. Upon multivariate analysis, anxiety (OR 8.56), multimorbidity (OR 2.18), and age (OR 2.73) emerged as independently associated with frailty (p < .001, p = .005, and p < .001, respectively). CONCLUSIONS: Among postmenopausal women with frailty, anxiety was detected in over two thirds of cases and was independently associated with frailty. This underscores the relevance of implementing anxiety screening in comprehensive care programs for postmenopausal women, with the goal of improving frailty through anxiety diagnosis and treatment.


Asunto(s)
Fragilidad , Humanos , Femenino , Anciano , Fragilidad/epidemiología , Posmenopausia , Estudios Transversales , Menopausia , Ansiedad/epidemiología
2.
Microsc Microanal ; 30(1): 14-26, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38214892

RESUMEN

In this study, a novel application of synchrotron X-ray nanotomography based on high-resolution full-field transmission X-ray microscopy for characterizing the structure and morphology of micrometric hollow polymeric fibers is presented. By employing postimage analysis using an open-source software such as Tomviz and ImageJ, various key parameters in fiber morphology, including diameter, wall thickness, wall thickness distribution, pore size, porosity, and surface roughness, were assessed. Electrospun polycaprolactone fibers with micrometric diameters and submicrometric features with induced porosity via gas dissolution foaming were used to this aim. The acquired synchrotron X-ray nanotomography data were analyzed using two approaches: 3D tomographic reconstruction and 2D radiographic projection-based analysis. The results of the combination of both approaches demonstrate unique capabilities of this technique, not achievable by other available techniques, allowing for a full characterization of the internal and external morphology and structure of the fibers as well as to obtain valuable qualitative insights into the overall fiber structure.

3.
Plant Dis ; 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853333

RESUMEN

In Mexico, there are 29 native species of the genus Hymenocallis, where H. glauca is one of the most cultivated bulbous plants. It holds economic importance as it is commercialized as a potted plant and cut flower (Leszczyñska and Borys, 2001). In October 2023, field sampling was conducted in the Research Center in Horticulture and Native Plants (18°55'55" N, 98°24'02.8"W) of UPAEP University. H. glauca diseased plants were found in an area of 0.4 ha, with an incidence of 35% and an estimated severity of 45% on infected plants in vegetative stage. The symptoms included chlorosis of foliage, necrosis at the base of the stem, and soft rot with abundant white to gray mycelium and abundant production of black, irregular sclerotia of approximately 3.5 mm diameter. Finally, the plants wilted and died. The fungus was isolated from 40 symptomatic plants. Sclerotia were collected, disinfested with 3% NaOCl for one minute, rinsed with sterile distilled water (SDW), and plated on Petri dishes containing potato dextrose agar (PDA) with sterile forceps. Subsequently, a sterile dissecting needle was used to place fragments of mycelium directly on Petri dishes with PDA. Plates were incubated at 23 °C in dark for 7 days. One isolate was obtained from each diseased plant by the hyphal-tip method (20 isolates from sclerotia and 20 from mycelium). After 7 days, colonies had fast-growing, dense, and cottony-white aerial mycelium forming irregular sclerotia of 3.57 ± 0.59 mm (mean ± standard deviation, n=100). In each Petri dish there were produced 21.5 ± 7.9 sclerotia (mean ± standard deviation, n=40), after 11 days; these were initially white and gradually turned black. The isolates were tentatively identified as Sclerotinia sclerotiorum based on morphological characteristics (Saharan and Mehta 2008). Two representative isolates were chosen for molecular identification and genomic DNA was extracted by the CTAB protocol. The ITS region and the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene were amplified and sequenced (Staats et al. 2005; White et al. 1990). The sequences of a representative isolate (SsHg3) were deposited in GenBank (ITS- PP094578; G3PDH- PP101843). BLAST analysis of the partial sequences ITS (519 bp), and G3PDH (950 bp) showed 100% similarity to S. sclerotiorum isolates (GenBank: MG249967, MW082601). Pathogenicity was confirmed by inoculating 30 H. glauca plants in vegetative stage grown in pots with sterile soil. Ten sclerotia were deposited at the base of the stem, 10 mm below the soil surface. As control treatment, SDW was applied to 10 plants. The plants were placed in a greenhouse at 23 °C and 90% relative humidity. After 17 days, all inoculated plants displayed symptoms similar to those observed in the field, while no symptoms were observed on the controls. The fungus was re-isolated from the inoculated plants as described above, fulfilling Koch's postulates. The pathogenicity tests were repeated three times. S. sclerotiorum has been reported causing white mold on other bulbous plants, like fennel (Foeniculum vulgare) in Korea (Choi et al. 2015). To our knowledge, this is the first report of S. sclerotiorum causing white mold on H. glauca in Mexico. Information about diseases affecting this plant is very limited, so this research is essential for developing integrated management strategies and preventing spread to other production areas.

4.
Haematologica ; 108(1): 150-160, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35443559

RESUMEN

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Adulto , Humanos , Persona de Mediana Edad , Médula Ósea , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/terapia , Mutación , Pronóstico , Anciano
5.
Haematologica ; 108(7): 1900-1908, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36779595

RESUMEN

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) and inferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan. Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Adulto , Humanos , Adolescente , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/terapia , Busulfano/uso terapéutico , Melfalán , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento Pretrasplante , Vidarabina/uso terapéutico
6.
Mult Scler ; 29(14): 1795-1807, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37905526

RESUMEN

BACKGROUND: Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF. OBJECTIVE: To report final outcomes from EVOLVE-MS-1. METHODS: EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory. RESULTS: Overall, 75.7% (800/1057) of patients completed the study; median exposure was 1.8 (range: 0.0-2.0) years. AEs occurred in 938 (88.7%) patients, mostly of mild (28.9%) or moderate (50.3%) severity. DRF was discontinued due to AEs in 85 (8.0%) patients, with < 2% discontinuing due to GI or flushing/flushing-related AEs. At Week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (72.7%; p < 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11-0.15). CONCLUSION: DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Humanos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Inmunosupresores/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Dimetilfumarato/efectos adversos , Recurrencia
7.
Cogn Process ; 24(3): 339-351, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36934379

RESUMEN

The processing of emotional facial expressions helps people to adjust to the physical and social environment. Furthermore, mental disorders such as anxiety have been linked to attentional biases in the processing of this type of information. Nevertheless, there are still contradictory results that might be due to the methodology used and to individual differences in the manifestation of anxiety. Our research goal was to use 24 facial priming sequences to analyse attentional biases in the detection of facial expressions of fear, considering the levels and the ways in which individuals express anxiety. With higher levels of cognitive anxiety and general trait anxiety, those sequences that began in the upper half (vs. lower half) elicited a speedier response in the detection of fear. The results are discussed within the context of other techniques and disorders that prompt a deficit in the processing of facial information.


Asunto(s)
Sesgo Atencional , Humanos , Atención/fisiología , Ansiedad/psicología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Emociones , Expresión Facial
8.
World J Microbiol Biotechnol ; 39(9): 232, 2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37349471

RESUMEN

The fungal cell wall protects fungi against threats, both biotic and abiotic, and plays a role in pathogenicity by facilitating host adhesion, among other functions. Although carbohydrates (e.g. glucans, chitin) are the most abundant components, the fungal cell wall also harbors ionic proteins, proteins bound by disulfide bridges, alkali-extractable, SDS-extractable, and GPI-anchored proteins, among others; the latter consisting of suitable targets which can be used for fungal pathogen control. Pseudocercospora fijiensis is the causal agent of black Sigatoka disease, the principal threat to banana and plantain worldwide. Here, we report the isolation of the cell wall of this pathogen, followed by extensive washing to eliminate all loosely associated proteins and conserve those integrated to its cell wall. In the HF-pyridine protein fraction, one of the most abundant protein bands was recovered from SDS-PAGE gels, electro-eluted and sequenced. Seven proteins were identified from this band, none of which were GPI-anchored proteins. Instead, atypical (moonlight-like) cell wall proteins were identified, suggesting a new class of atypical proteins, bound to the cell wall by unknown linkages. Western blot and histological analyses of the cell wall fractions support that these proteins are true cell wall proteins, most likely involved in fungal pathogenesis/virulence, since they were found conserved in many fungal pathogens.


Asunto(s)
Ascomicetos , Musa , Enfermedades de las Plantas/microbiología , Pared Celular , Musa/microbiología , Proteínas Ligadas a GPI , Proteínas Fúngicas/genética
9.
Eur J Neurol ; 29(7): 2015-2023, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35247022

RESUMEN

BACKGROUND AND PURPOSE: The aim was to evaluate whether adaptive NKG2C+ natural killer (NK) cells, characterized by enhanced antibody-dependent cell cytotoxicity (ADCC), may influence time to B cell repopulation after rituximab treatment in multiple sclerosis (MS) patients. METHODS: This was a prospective observational study of MS patients treated with rituximab monitoring peripheral B cells for repeated doses. B cell repopulation was defined as CD19+ cells above 2% of total lymphocytes, classifying cases according to the median time of B cell repopulation as early or late (≤9 months, >9 months, respectively). Basal NK cell immunophenotype and in vitro ADCC responses induced by rituximab were assessed by flow cytometry. RESULTS: B cell repopulation in 38 patients (24 relapsing-remitting MS [RRMS]; 14 progressive MS) was classified as early (≤9 months, n = 19) or late (>9 months, n = 19). RRMS patients with late B cell repopulation had higher proportions of NKG2C+ NK cells compared to those with early repopulation (24.7% ± 16.2% vs. 11.3% ± 10.4%, p < 0.05), and a direct correlation between time to B cell repopulation and percentage of NKG2C+ NK cells (R 0.45, p < 0.05) was observed. RRMS cases with late repopulation compared with early repopulation had a higher secretion of tumor necrosis factor α and interferon γ by NK cells after rituximab-dependent NK cell activation. The NK cell immunophenotype appeared unrelated to B cell repopulation in progressive MS patients. CONCLUSIONS: Adaptive NKG2C+ NK cells in RRMS may be associated with delayed B cell repopulation after rituximab, a finding probably related to enhanced depletion of B cells exerted by NK-cell-mediated ADCC, pointing to the use of personalized regimens with anti-CD20 monoclonal antibody therapy in some patients.


Asunto(s)
Esclerosis Múltiple , Anticuerpos Monoclonales/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos , Humanos , Células Asesinas Naturales , Esclerosis Múltiple/tratamiento farmacológico , Rituximab/farmacología , Rituximab/uso terapéutico
10.
Br J Nutr ; 128(6): 1170-1179, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-34713791

RESUMEN

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles (Pfor trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (ß (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.


Asunto(s)
Dieta Mediterránea , Síndrome Metabólico , Humanos , Anciano , Depresión/epidemiología , Estudios Transversales , Estudios de Seguimiento , Dieta
11.
BMC Pulm Med ; 22(1): 169, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35488330

RESUMEN

BACKGROUND: Frequent and highly prevalent as comorbidities in Chronic Obstructive Pulmonary Disease (COPD) patients, both depression and anxiety seem to have an impact on COPD prognosis. However, they are underdiagnosed and rarely treated properly. AIM: To establish the prevalence of depression and anxiety in patients admitted for Acute Exacerbation of COPD (AECOPD) and determine their influence on COPD prognosis. METHODS: Prospective observational study conducted from October 1, 2016 to October 1, 2018 at the following centers in Galicia, Spain: Salnés County Hospital, Arquitecto Marcide, and Clinic Hospital Complex of Santiago de Compostela. Patients admitted for AECOPD who agreed to participate and completed the anxiety and depression scale (HADS) were included in the study. RESULTS: 288 patients (46.8%) were included, mean age was 73.7 years (SD 10.9), 84.7% were male. 67.7% patients were diagnosed with probable depression, and depression was established in 41.7%; anxiety was probable in 68.2% and established in 35.4%. 60.4% of all patients showed symptoms of both anxiety and depression. Multivariate analysis relates established depression with a higher risk of late readmission (OR 2.06, 95% CI 1.28; 3.31) and a lower risk of mortality at 18 months (OR 0.57, 95% CI 0.37; 0.90). CONCLUSION: The prevalence of anxiety and depression in COPD patients is high. Depression seems to be an independent factor for AECOPD, so early detection and a multidisciplinary approach could improve the prognosis of both entities. The study was approved by the Ethical Committee of Galicia (code 2016/460).


Asunto(s)
Depresión , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Ansiedad/epidemiología , Comorbilidad , Depresión/epidemiología , Femenino , Humanos , Masculino , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
12.
Microsc Microanal ; : 1-12, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35300749

RESUMEN

Three independent analysis methods were developed to investigate the distribution of solid mass in foams analyzed by X-ray tomography with effective pixel sizes larger than the thickness of the solid network (sub-pixel conditions). Validation of the methods was achieved by a comparison with the results obtained employing high-resolution tomography for the same set of foams. The foams showed different solid mass distribution, which varied from being preferentially located on the edges, with a fraction of mass in the struts nearing 0.6, to materials in which the fraction of mass in the struts was low, under 0.15. In all cases, the accuracy of the proposed approaches was greater for materials with a higher fraction of mass in the struts. The method based on deconvolution of the attenuation probability density function yielded the closest results to the high-resolution characterizations. In contrast, analysis of the solid matrix thickness distribution after watershed segmentation, and binarization of high thickness regions (struts segmentation) required normalization through macroscopic measurements and revealed higher deviations with respect to the high-resolution results. However, segmentation-based methods allowed investigation of the heterogeneity of the fraction of mass in the struts along the sample.

13.
Int J Mol Sci ; 23(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36012636

RESUMEN

Lipases are enzymes that hydrolyze triglycerides to fatty acids and glycerol. A typical element in lipases is a conserved motif of five amino acids (the pentapeptide), most commonly G-X-S-X-G. Lipases with the pentapeptide A-X-S-X-G are present in species of Bacillus, Paucimonas lemoignei, and the yeast Trichosporon asahii; they are usually thermotolerant and solvent resistant. Recently, while searching for true lipases in the Trichoderma harzianum genome, one lipase containing the pentapeptide AHSMG was identified. In this study, we cloned from T. harzianum strain B13-1 the lipase ID135964, renamed here as ThaL, which is 97.65% identical with the reference. We found that ThaL is a lid-containing true lipase of cluster III that belongs to a large family comprising highly conserved proteins in filamentous fungi in the orders Hypocreales and Glomerellales, in which predominantly pathogenic fungi are found. ThaL was expressed in conidia, as well as in T. harzianum mycelium, where it was cultured in liquid minimal medium. These results-together with the amino acid composition, absence of a signal peptide, mitochondrial sorting prediction, disordered regions in the protein, and lineage-specific phylogenetic distribution of its homologs-suggest that ThaL is a non-canonical effector. In summary, AHSMG-lipase is a novel lipase family in filamentous fungi, and is probably involved in pathogenicity.


Asunto(s)
Bacillus , Hypocreales , Bacillus/metabolismo , Hongos/metabolismo , Hypocreales/metabolismo , Lipasa/metabolismo , Filogenia , Pseudomonas/metabolismo
14.
J Chem Inf Model ; 61(7): 3213-3231, 2021 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-34191520

RESUMEN

In silico prediction of antileishmanial activity using quantitative structure-activity relationship (QSAR) models has been developed on limited and small datasets. Nowadays, the availability of large and diverse high-throughput screening data provides an opportunity to the scientific community to model this activity from the chemical structure. In this study, we present the first KNIME automated workflow to modeling a large, diverse, and highly imbalanced dataset of compounds with antileishmanial activity. Because the data is strongly biased toward inactive compounds, a novel strategy was implemented based on the selection of different balanced training sets and a further consensus model using single decision trees as the base model and three criteria for output combinations. The decision tree consensus was adopted after comparing its classification performance to consensuses built upon Gaussian-Naïve-Bayes, Support-Vector-Machine, Random-Forest, Gradient-Boost, and Multi-Layer-Perceptron base models. All these consensuses were rigorously validated using internal and external test validation sets and were compared against each other using Friedman and Bonferroni-Dunn statistics. For the retained decision tree-based consensus model, which covers 100% of the chemical space of the dataset and with the lowest consensus level, the overall accuracy statistics for test and external sets were between 71 and 74% and 71 and 76%, respectively, while for a reduced chemical space (21%) and with an incremental consensus level, the accuracy statistics were substantially improved with values for the test and external sets between 86 and 92% and 88 and 92%, respectively. These results highlight the relevance of the consensus model to prioritize a relatively small set of active compounds with high prediction sensitivity using the Incremental Consensus at high level values or to predict as many compounds as possible, lowering the level of Incremental Consensus. Finally, the workflow developed eliminates human bias, improves the procedure reproducibility, and allows other researchers to reproduce our design and use it in their own QSAR problems.


Asunto(s)
Leishmania , Relación Estructura-Actividad Cuantitativa , Teorema de Bayes , Ensayos Analíticos de Alto Rendimiento , Humanos , Reproducibilidad de los Resultados
15.
Gynecol Endocrinol ; 37(3): 269-272, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33480311

RESUMEN

OBJECTIVE: Endothelial dysfunction and denudation are considered a first step in atherosclerosis. Endothelial proliferation is key for cellular repair. The effect of bazedoxifene on the vascular endothelium has not been explored. We investigated the effect of bazedoxifene on endothelial cell proliferation. METHODS: Primary cultures from human umbilical artery endothelial cells were used in dose-response experiments (0.1, 1.0, and 10.0 EC50 dose) with bazedoxifene, estradiol, raloxifene and a combination of bazedoxifene and estradiol. Proliferation was assessed with the XTT colorimetric cell-proliferation assay. The possible participation of cyclins A, B, D1 and p27Kip1 was analyzed by the measurement of their expression at both the protein and the gene levels. RESULTS: A significant increase of similar size for cell proliferation was obtained with bazedoxifene, estradiol and raloxifene, but no significant change was observed for the association of bazedoxifene and estradiol. The impact was detected at the first 0.1 EC50 dose and was not dose-dependent. Estradiol achieved a significant increase in the protein expression of cyclin A and p27Kip1, but no change was detected for the other compounds at either the gene or protein level. CONCLUSION: Bazedoxifene demonstrated a proliferative effect of similar size to estradiol in cultured human umbilical artery endothelial cells. The molecular mechanisms need further investigation.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Indoles/farmacología , Proliferación Celular/genética , Células Cultivadas , Ciclina A/genética , Ciclina A/metabolismo , Ciclina B/genética , Ciclina B/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Endoteliales/fisiología , Endotelio Vascular/citología , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Recién Nacido , Embarazo , Arterias Umbilicales/citología
16.
J Med Internet Res ; 23(9): e28766, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34550089

RESUMEN

Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients' ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters; mediate the development of benefit-to-burden criteria for innovative technology; and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments.


Asunto(s)
Enfermedad de la Neurona Motora , Tecnología Biomédica , Cuidadores , Personal de Salud , Humanos , Enfermedad de la Neurona Motora/diagnóstico , Enfermedad de la Neurona Motora/terapia , Tecnología
17.
Sensors (Basel) ; 21(24)2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34960385

RESUMEN

This study proposes a new index to measure the resilience of an individual to stress, based on the changes of specific physiological variables. These variables include electromyography, which is the muscle response, blood volume pulse, breathing rate, peripheral temperature, and skin conductance. We measured the data with a biofeedback device from 71 individuals subjected to a 10-min psychophysiological stress test. The data exploration revealed that features' variability among test phases could be observed in a two-dimensional space with Principal Components Analysis (PCA). In this work, we demonstrate that the values of each feature within a phase are well organized in clusters. The new index we propose, Resilience to Stress Index (RSI), is based on this observation. To compute the index, we used non-supervised machine learning methods to calculate the inter-cluster distances, specifically using the following four methods: Euclidean Distance of PCA, Mahalanobis Distance, Cluster Validity Index Distance, and Euclidean Distance of Kernel PCA. While there was no statistically significant difference (p>0.01) among the methods, we recommend using Mahalanobis, since this method provides higher monotonic association with the Resilience in Mexicans (RESI-M) scale. Results are encouraging since we demonstrated that the computation of a reliable RSI is possible. To validate the new index, we undertook two tasks: a comparison of the RSI against the RESI-M, and a Spearman correlation between phases one and five to determine if the behavior is resilient or not. The computation of the RSI of an individual has a broader scope in mind, and it is to understand and to support mental health. The benefits of having a metric that measures resilience to stress are multiple; for instance, to the extent that individuals can track their resilience to stress, they can improve their everyday life.


Asunto(s)
Biorretroalimentación Psicológica , Aprendizaje Automático , Electromiografía , Frecuencia Cardíaca , Humanos , Análisis de Componente Principal
18.
J Environ Manage ; 294: 112917, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34119983

RESUMEN

The interaction between climate change and biological invasions is a global conservation challenge with major consequences for invasive species management. However, our understanding of this interaction has substantial knowledge gaps; this is particularly relevant for invasive snakes on islands because they can be a serious threat to island ecosystems. Here we evaluated the potential influence of climate change on the distribution of invasive snakes on islands, using the invasion of the California kingsnake (Lampropeltis californiae) in Gran Canaria. We analysed the potential distribution of L. californiae under current and future climatic conditions in the Canary Islands, with the underlying hypothesis that the archipelago might be suitable for the species under these climate scenarios. Our results indicate that the Canary Islands are currently highly suitable for the invasive snake, with increased suitability under the climate change scenarios tested here. This study supports the idea that invasive reptiles represent a substantial threat to near-tropical regions, and builds on previous studies suggesting that the menace of invasive reptiles may persist or even be exacerbated by climate change. We suggest future research should continue to fill the knowledge gap regarding invasive reptiles, in particular snakes, to clarify their potential future impacts on global biodiversity.


Asunto(s)
Cambio Climático , Ecosistema , Animales , California , Islas , Serpientes , España
19.
Biol Blood Marrow Transplant ; 26(10): 1930-1936, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32649981

RESUMEN

Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P < .0001). The 2-year incidence of transplantation-related mortality adjusted for age and conditioning regimen intensity was higher after umbilical cord blood transplantation compared with HLA-haploidentical related donor transplantation (31% versus 18%; P = .008); however, there were no between-group differences in the 2-year adjusted incidence of relapse (30% versus 34%; P = .51), overall survival (54% versus 57%; P = .66), or disease-free survival (43% versus 47%; P = .46). Our findings show that the use of HLA-haploidentical and umbilical cord blood transplants expands the access to transplantation with comparable leukemia-free and overall survival for African Americans with hematologic malignancies.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Negro o Afroamericano , Sangre Fetal , Neoplasias Hematológicas/terapia , Prueba de Histocompatibilidad , Humanos
20.
Biol Blood Marrow Transplant ; 26(8): 1459-1468, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32434056

RESUMEN

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Factores de Riesgo , Acondicionamiento Pretrasplante
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