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1.
Front Immunol ; 15: 1252258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938565

RESUMO

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mieloide Aguda , Neoplasia Residual , Células Neoplásicas Circulantes , Neoplasia Residual/diagnóstico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/sangue , Células Neoplásicas Circulantes/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia Líquida/métodos , Adulto , Biomarcadores Tumorais/sangue , Idoso , Prognóstico , Ácidos Nucleicos Livres/sangue
3.
Front Immunol ; 14: 1188818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342332

RESUMO

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.


Assuntos
DNA Tumoral Circulante , Linfoma Folicular , Receptores de Antígenos Quiméricos , Humanos , Feminino , DNA Tumoral Circulante/genética , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia , Terapia Baseada em Transplante de Células e Tecidos
4.
Leukemia ; 37(3): 659-669, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596983

RESUMO

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10-4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10-57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10-89.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials.


Assuntos
Linfoma Folicular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Biomarcadores , Biópsia Líquida , Sequenciamento de Nucleotídeos em Larga Escala
5.
Eur Respir J ; 61(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36104291

RESUMO

BACKGROUND: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit. METHODS: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings. RESULTS: We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results. CONCLUSIONS: These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2 , Transcriptoma , Estado Terminal , Unidades de Terapia Intensiva
6.
J Neurol ; 270(1): 13-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36178541

RESUMO

Headache is among the most frequently reported symptoms after resolution of COVID-19. We assessed structural brain changes using T1- and diffusion-weighted MRI processed data from 167 subjects: 40 patients who recovered from COVID-19 but suffered from persistent headache without prior history of headache (COV), 41 healthy controls, 43 patients with episodic migraine and 43 patients with chronic migraine. To evaluate gray matter and white matter changes, morphometry parameters and diffusion tensor imaging-based measures were employed, respectively. COV patients showed significant lower cortical gray matter volume and cortical thickness than healthy subjects (p < 0.05, false discovery rate corrected) in the inferior frontal and the fusiform cortex. Lower fractional anisotropy and higher radial diffusivity (p < 0.05, family-wise error corrected) were observed in COV patients compared to controls, mainly in the corpus callosum and left hemisphere. COV patients showed higher cortical volume and thickness than migraine patients in the cingulate and frontal gyri, paracentral lobule and superior temporal sulcus, lower volume in subcortical regions and lower curvature in the precuneus and cuneus. Lower diffusion metric values in COV patients compared to migraine were identified prominently in the right hemisphere. COV patients present diverse changes in the white matter and gray matter structure. White matter changes seem to be associated with impairment of fiber bundles. Besides, the gray matter changes and other white matter modifications such as axonal integrity loss seemed subtle and less pronounced than those detected in migraine, showing that persistent headache after COVID-19 resolution could be an intermediate state between normality and migraine.


Assuntos
COVID-19 , Transtornos de Enxaqueca , Substância Branca , Humanos , Imagem de Tensor de Difusão , COVID-19/complicações , COVID-19/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtornos de Enxaqueca/diagnóstico por imagem , Cefaleia/diagnóstico por imagem , Cefaleia/etiologia , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Imageamento por Ressonância Magnética
9.
J Asthma ; 59(5): 1005-1011, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33653213

RESUMO

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.


Assuntos
Antiasmáticos , Asma , Eosinofilia Pulmonar , Corticosteroides/uso terapêutico , Adulto , Idoso , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/tratamento farmacológico , Estudos Retrospectivos
10.
CNS Spectr ; : 1-9, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34121647

RESUMO

BACKGROUND: Few studies have analyzed compulsive buying behavior in relation to a specific product. Smartphones are hugely popular products today, especially among young people. These two aspects have motivated this research into the compulsive buying behavior of Smartphones by university students. METHODS: To study this behavior, the main features that differentiate compulsive buyers from those that are not are analyzed, and their risk profiles are obtained through a discrete choice model. RESULTS: Sociodemographic features that define buyers with the greatest propensity to compulsiveness are younger age, longer time spent daily using social networks, higher spending on the acquisition of Smartphones and having owned a greater number of these devices. These buyers also show shopping addiction and greater feelings of guilt after the purchase as well as more positive and negative affective states when purchasing Smartphones. CONCLUSIONS: This analysis not only determines the characteristics that define young individuals with a tendency toward compulsiveness in Smartphone purchases, but also contributes to quantifying the probability of having this tendency.

11.
Rev. chil. obstet. ginecol. (En línea) ; 86(1): 23-32, feb. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1388627

RESUMO

OBJETIVO: Analizar si los casos positivos de cribado combinado de trisomía 21 (t21) o trisomía 18 (t18) en ausencia de aneuploidía (falsos positivos- FP) se relacionan con complicaciones de la gestación, ajustando por factores demográficos y clínicos de riesgo. MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles anidado en una cohorte de pacientes que acudieron para cribado del primer trimestre. Los casos fueron las pacientes con FP de riesgo combinado de t21 superior a 1/270 o riesgo de t18 superior a 1/100. Se consideraron complicaciones de la gestación: óbito fetal, parto prematuro menor de 34 semanas o prematuro menor de 37 semanas, preeclampsia, retrasos de crecimiento, pequeño para la edad gestacional (CIR, PEG) y diabetes gestacional (DG). Se ajustó por obesidad, edad, paridad, tabaquismo, y técnicas de reproducción asistida. RESULTADO: Se obtuvieron 204 casos de FP, 149 FP para trisomía 21, 41 para trisomía 18, y 14 FP para ambos riesgos. Se encontró asociación estadísticamente significativa de FP t21 con óbito fetal (OR=3,5; ic95% 1,4-8,7; p=0,01), parto prematuro menor de 37 semanas (OR=2,2; IC95% 1,4-3,4; p=0,001), preeclampsia (OR =2,6; IC95% 1,17-6,1; p=0,02), PEG (OR =2,2; IC95% 1,2-4,1; p=0,02), CIR (OR=2,8; IC95% 1,6-5,1; p=0,001), y DG (OR=2,1; IC95% 1,2-3,7; p=0,01). Los FP t18 se asociaron con óbito (OR=8,9; IC95% 2,9-27; p=0,002). CONCLUSIÓN: Los FP del cribado del primer trimestre, para trisomía 21 y trisomía 18, se asocian con resultados obstétricos adversos.


We have studied whether positive cases of combined trisomy 21 (t21) or 18 (t18) screening in the absence of aneuploidy (false positives -FP-) are related to pregnancy complications adjusting for demographic and clinical risk factors. METHODS: Retrospective case-control study nested in a cohort of patients who came for first trimester aneuploidy screening. The cases were patients with FP combined risk of t21 (greater than 1/270) or t18 risk (greater than 1/100). The control group was a sample of patients with low-risk screening. We considered pregnancy complications: stillbirth, premature delivery before 34 and 37 weeks, preeclampsia, growth retardation, small for gestational age (FGR, SGA), and gestational diabetes (GD). Or were adjusted for obesity, age, parity, smoking, and assisted reproduction techniques. RESULTS: 204 cases of FP were obtained, 149 FP for trisomy 21, 41 for trisomy 18, and 14 FP for both risks. A statistically significant association between t21 FP was found with stillbirth (OR = 3.5; 95% CI 1.4-8.7; p = 0.01), preterm delivery less than 37 weeks (OR = 2.2; 95% CI 1.4-3.4; p = 0.001), preeclampsia (OR = 2.6; 95% CI 1.17-6.1; p = 0.02), SGA (OR = 2.2; 95% CI 1, 2-4.1; p = 0.02), FGR (OR = 2.8; 95% CI 1.6-5.1; p = 0.001), and GD (OR = 2.1; 95% CI 1.2 −3.7; p = 0.01). FP t18s were associated with fetal loss (OR= 8.9 (95% CI 2.9-27) p = 0.002. CONCLUSION: FP from first trimester screening for t21 and t18 are associated with adverse obstetric outcomes.


Assuntos
Humanos , Feminino , Gravidez , Síndrome de Down/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Trissomia/diagnóstico , Estudos de Casos e Controles , Programas de Rastreamento , Valor Preditivo dos Testes , Fatores de Risco , Síndrome de Down/epidemiologia , Reações Falso-Positivas , Síndrome da Trissomía do Cromossomo 18/epidemiologia
12.
Sci Rep ; 11(1): 446, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432056

RESUMO

It is known that the harmful presence of the wild cochineal (Dactylopius opuntiae), unlike the fine cochineal (Dactylopius coccus), in prickly pear crops of farmers leads to consider it as one of the major pests for this crop. In this study, we present the implementation of an optical setup that ensures the measurement of the in-vivo fluorescence spectra of wild cochineals ranging in size from 440 to 1190 µm in their natural habitat achieved by developing a reproduction model adopted from available literature. It was observed that in-vivo fluorescence spectra of these insects were comprised in the spectral region of 570-760 nm, showing a proportional dependence between the fluorescence intensity emitted and the cochineal size. In addition, we have considered other spectral parameters to perform the comparison between fluorescence spectra of the different cochineal sizes. These results provide the basis for the development of novel methodologies and equipment aimed towards the early detection of this pest in prickly pear crops from its early growth stages (nymph I and II).

14.
Pain Med ; 21(11): 2997-3011, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33040149

RESUMO

OBJECTIVE: This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine. DESIGN: Cohort study. SETTING: Spanish community. SUBJECTS: Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition. METHODS: Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed. RESULTS: Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters. CONCLUSIONS: Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients.


Assuntos
Substância Cinzenta , Transtornos de Enxaqueca , Estudos de Casos e Controles , Estudos de Coortes , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/diagnóstico por imagem
15.
Brain Sci ; 10(10)2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33036306

RESUMO

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine.

16.
Perspect. nutr. hum ; 22(1): 61-69, ene.-jun. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1346665

RESUMO

Resumen Antecedentes: las carreras universitarias de la salud deben promover estilos de vida sanos. Objetivo: identificar la relación entre el perfil del estilo de vida, la percepción del estilo de vida saludable y la percepción sobre la carrera de Nutriología de los estudiantes de la Universidad Autónoma de Tlaxcala. Materiales y métodos: tipo de estudio transversal y correlacional. Se evaluaron 145 estudiantes de ambos sexos con tres instrumentos aplicados en un mismo momento. Los datos se reportaron en medianas y se compararon con la prueba U de Mann-Whitney. Se realizaron las pruebas de correlación entre las tres variables con r de Pearson. Resultados: el perfil del estilo de vida tuvo una puntuación diferenciada por sexo (p=0,002); la percepción de estilos de vida saludable (p=0,123) y la percepción de su disciplina (p=0,775) fueron similares entre sexos. Sobresale que el estilo de vida se correlacionó positivamente con la percepción de este (r=0,35; p=0,002). La percepción del estilo de vida se relaciona con la percepción de la carrera (r=0,202; p=0,015), pero no se encontró correlación entre el estilo de vida y la percepción de la disciplina (r=0,08; p=0,34). Conclusiones: a mayor perfil de estilo de vida satisfactorio más alta es la percepción de un estilo de vida saludable.


Abstract Background: University majors that focus on health should promote healthy lifestyles. Objective: Identify the relationship between actual lifestyles, perceptions of healthy lifestyles, and perceptions surrounding being a Nutrition major in the Autonomous University of Tlaxcala. Materials and Methods: Cross-sectional and cor relational study. 145 students, both male and female, were evaluated with the application of three tools simul taneously. Data were reported as medians and were compared using the Mann-Whitney U test. Correlation tests were performed between the three variables using Pearson's r. Results: Lifestyles of students varied by male vs. female (p=0.002). Healthy lifestyle perceptions (p = 0.123) and students' perception of their discipline (p = 0.775) were similar for both genders. It can be highlighted that lifestyle was positively correlated with the perception of it (r = 0.35; p = 0.002). Lifestyle perception was correlated with the perception of their major of study (nutrition) (r = 0.202; p = 0.015), but no correlation was found between lifestyle and discipline perception (r=0.08; p=0.34). Conclusions: The higher the profile of a satisfying lifestyle, the higher the perception of a healthy lifestyle.


Assuntos
Estatísticas não Paramétricas , Estilo de Vida Saudável
17.
J Food Biochem ; 44(5): e13191, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32160647

RESUMO

Oxidative stress is associated with several chronic diseases. It is acknowledged that molecules damaged by reactive oxygen species activate the inflammatory process and that this response increases the production of free radicals. Modifications in a diet can improve or decrease redox state markers. The aim of this revision was to provide an update of clinical controlled trials, to assess changes in diet and markers of oxidative stress in subjects with metabolic diseases. They were investigated randomized controlled intervention studies (RCTs) published in MEDLINE (U.S. National Library of Medicine, National Institutes of Health) that were conducted in subjects with obesity, hypertension, diabetes, or dyslipidemia; with dietary intervention; where markers of oxidative stress have been evaluated and published in the last 5 years. Food antioxidants, hypocaloric diets with loss of adipose tissue, substitution of animal protein by vegetable, and changes in the microbiota improve antioxidant status in people with chronic disease. PRACTICAL APPLICATIONS: Hyperglycemia in diabetes mellitus and adipose tissue in obesity are known to trigger oxidative stress. Oxidative stress, in turn, decreases insulin sensitivity and favors an inflammatory state producing adhesion molecules. Oxidative stress and adhesion molecules, can increase blood pressure and oxidation of lipoproteins, that ultimately could lead to a cerebrovascular event. Consumption of high-antioxidant and polyphenol foods increases plasma antioxidant capacity and decreases oxidative stress markers in people with diabetes, obesity, hypertension, and hypertriglyceridemia. In addition, weight loss caused by caloric restriction with or without exercise increases the endogenous antioxidant capacity. Therefore, it is likely that the combination of a hypocaloric diet with a high content of antioxidants and polyphenols will have a greater effect. Other dietary changes with antioxidant effect, such as the substitution of animal for vegetable protein or the addition of fiber, might be mediated by changes in the microbiota. However, this aspect requires further study.


Assuntos
Hiperglicemia , Obesidade , Animais , Antioxidantes , Dieta Redutora , Estresse Oxidativo , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos
18.
Fish Shellfish Immunol ; 99: 86-98, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004617

RESUMO

PIM kinases are a family of serine/threonine protein kinases that potentiate the progression of the cell cycle and inhibit apoptosis. Because of this, they are considered to be proto-oncogenes, and they represent an interesting target for the development of anticancer drugs. In mammals, three PIM kinases exist (PIM-1, PIM-2 and PIM-3), and different inhibitors have been developed to block their activity. In addition to their involvement in cancer, some publications have reported that the PIM kinases have pro-viral activity, and different mechanisms where PIM kinases favour viral infections have been proposed. Zebrafish possess more than 300 Pim kinase members in their genome, and by using RNA-Seq analysis, we found a high number of Pim kinase genes that were significantly induced after infection with spring viraemia of carp virus (SVCV). Moreover, analysis of the miRNAs modulated by this infection revealed that some of them could be involved in the post-transcriptional regulation of Pim kinase abundance. To elucidate the potential role of the 16 overexpressed Pim kinases in the infectivity of SVCV, we used three different pan-PIM kinase inhibitors (SGI-1776, INCB053914 and AZD1208), and different experiments were conducted both in vitro and in vivo. We observed that the PIM kinase inhibitors had a protective effect against SVCV, indicating that, similar to what is observed in mammals, PIM kinases are beneficial for the virus in zebrafish. Moreover, zebrafish Pim kinases seem to facilitate viral entry into the host cells because when ZF4 cells were pre-incubated with the virus and then were treated with the inhibitors, the protective effect of the inhibitors was abrogated. Although more investigation is necessary, these results show that pan-PIM kinase inhibitors could serve as a useful treatment for preventing the spread of viral diseases.


Assuntos
Rim/enzimologia , Proteínas Proto-Oncogênicas c-pim-1/genética , Infecções por Rhabdoviridae/veterinária , Internalização do Vírus/efeitos dos fármacos , Peixe-Zebra/virologia , Animais , Apoptose , Compostos de Bifenilo/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Imidazóis/farmacologia , Rim/virologia , Poli I-C/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Piridazinas/farmacologia , RNA-Seq , Rhabdoviridae , Tiazolidinas/farmacologia , Peixe-Zebra/anatomia & histologia
19.
Salud pública Méx ; 62(1): 87-95, ene.-feb. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1365995

RESUMO

Resumen: Objetivo: Evaluar la relación entre calidad de vida laboral (CVL) y el desempeño organizacional (DO) de trabajadores de siete hospitales públicos, a partir del análisis de la influencia de la gestión directiva (GD) como mediadora de esta relación. Material y métodos: Se realizó un estudio transversal en 866 profesionales y directivos de hospitales públicos de Tlaxcala y de la Ciudad de México. La CVL fue medida con un instrumento validado, el DO con 34 indicadores y la GD con un instrumento diseñado para este estudio. Resultados: Los puntajes de gestión directiva, CVL, DO y GD fueron significativamente menores en los trabajadores de Tlaxcala. Los participantes que percibieron adecuada GD incrementaron 2.7 veces más la probabilidad de percibir elevada CVL y los participantes categorizados en elevada CVL presentaron 69% mayor probabilidad de tener adecuado DO. Conclusiones: La adecuada GD se asoció con una mejor CVL, lo que mostró ser una variable mediadora de la relación positiva entre CVL y DO.


Abstract: Objective: To assess the relationship between labor quality of life (LQL) and organizational workers performance (OWP) from seven public hospitals, analyzing the influence of the personnel management (PM) as mediator of this relationship. Materials and methods: A cross-sectional study was conducted in 866 professionals and managers of public hospitals from Tlaxcala and Mexico City. The LQL was assessed with a validated questionnaire, OWP with 34 indicators, and PM with an instrument designed for this study. Results: Mean scores of LQL, were significantly lower among workers from Tlaxcala. Participants who perceived an adequate PM, they increased at 2.7 times their likelihood of having highest LQL, and participants categorized in the high LQL presented 69% higher likelihood of having an adequate OWP. Conclusions: The appropriate PM was associated with greater LQL, showing to be a mediator variable between the positive relationship of CVL and the OWP.


Assuntos
Adulto , Feminino , Humanos , Masculino , Administração de Recursos Humanos em Hospitais , Qualidade de Vida , Desempenho Profissional/normas , Hospitais Públicos , Satisfação no Emprego , Estudos Transversais , Saúde Ocupacional , Eficiência Organizacional , México
20.
Rev. chil. obstet. ginecol. (En línea) ; 85(1): 36-46, feb. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1092773

RESUMO

INTRODUCCIÓN Y OBJETIVOS: La mayoría de las sociedades científicas recomiendan el parto vaginal del segundo gemelo siempre que el primer gemelo esté en presentación cefálica. En estos casos existe controversia cuánto tiempo transcurrido entre el parto de ambos es determinante en el resultado adverso del segundo gemelo. El objetivo de este estudio es examinar cómo influye dicho intervalo en el resultado perinatal precoz en nuestro Centro y el coste de las estancias neonatales y maternas. MÉTODOS: Estudio de cohortes retrospectivo entre mayo de 2014 y diciembre de 2018. Se comparó el resultado neonatal adverso estableciendo puntos de corte de intervalo entre el nacimiento de 10 y 30 minutos. Así mismo, se examinó la relación de otras variables del parto con el desenlace neonatal y se calcularon los costes de las estancias neonatales y maternas. RESULTADOS: Se incluyeron 128 partos gemelares vaginales asistidos en el Hospital Universitario Nuestra Señora de la Candelaria. Se evidenció triple tasa de resultado neonatal adverso en el grupo de más de 10 minutos (p=0,026 y OR 2,4) y tres veces peor en el de más de 30 minutos (p=0,013 y OR 6,4). Se obtuvo una correlación lineal negativa significativa entre el intervalo intergemelar y el pH umbilical. La prematuridad y el bajo peso al nacer fueron predictores de un mal desenlace neonatal. CONCLUSIONES: No parece recomendable que el intervalo intergemelar se prolongue más allá de los 30 minutos. Es seguro recomendar el parto vía vaginal en gestaciones gemelares siempre que el primero esté en presentación cefálica.


INTRODUCTION AND OBJECTIVES: Most scientific societies recommend vaginal delivery of the second twin when the first twin is in cephalic presentation. In these cases, there is controversy over how much inter-twin interval is decisive in the adverse outcome of the second twin. The aim of this study is to examine whether inter-twin delivery interval affects immediate perinatal outcome and the cost of neonatal and maternal stays. METHODS: Retrospective cohort study including 128 twin vaginal births attended in the Hospital Universitario Nuestra Señora de la Candelaria between May 2014 and December 2018. We compared the presence of composite adverse neonatal outcome by establishing interval cut-off points between birth of 10 and 30 minutes. Likewise, the relationship of other delivery associated variables with neonatal outcome was examined. Health care costs were calculated. RESULTS: There was a higher rate of composite adverse neonatal outcome in the 10 minute-group (p = 0.026, OR 2.4) and three times higher in the 30 minute-group (p = 0.013, OR 6.4). A significant negative linear correlation was obtained between birth interval and umbilical artery pH. Prematurity and low birth weight were predictors of a poor neonatal outcome. CONCLUSION: Our data suggests that inter-twin delivery interval shouldn't be prolonged beyond 30 minutes. Vaginal delivery is a safe option in twin gestations providing the first twin is in a cephalic presentation, regardless of the second twin presentation.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Gravidez de Gêmeos , Complicações do Trabalho de Parto , Fatores de Tempo , Intervalo entre Nascimentos , Resultado da Gravidez , Estudos Retrospectivos , Estudos de Coortes , Custos de Cuidados de Saúde , Complicações do Trabalho de Parto/economia
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