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1.
Curr Mol Pharmacol ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430757

RESUMO

BACKGROUND: The pseudo-cereal quinoa has attracted worldwide attention in recent years, due to it being considered a functional food. This stress-tolerant crop has historically been used by Andean cultures as a staple food. Nowadays, the consumption of quinoa in high-income countries is increasing due to it being associated with numerous health benefits, namely related with cardiovascular health. OBJECTIVE: We have carried out an extensive review on quinoa, including its main uses, applications, and components (nutrients, antinutrients, and bioactives) and their relationship with biological activities and cardiovascular health. Key findings and conclusions: Quinoa possess numerous activities, including protection against cardiovascular, metabolic, and degenerative diseases, improvement of the immune system, reduction of symptoms associated with post-menopause, and promotion of muscle mass increase. Some of quinoa's activities are due to its balanced amino acid profile, high fiber content, presence of phosphorus, iron, potassium, magnesium, vitamin E, and B vitamins. A plethora of bioactives can also be found in quinoa, such as phytosterols, saponins, phenolics, bioactive peptides, and phytoecdysteroids. More research is needed to better understand the mechanisms of action involved in the biological/therapeutic action of some quinoa components, namely those related with the potential to reduce cardiovascular disease (CVD) risk markers. The knowledge of factors that affect quinoa variability, such as processing conditions, is also of great importance for being able to obtain more benefits from this crop.

2.
Rev Esp Enferm Dig ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393337

RESUMO

Achalasia is usually treated endoscopically by dilations, injection of botulinum toxin or the most recent POEM treatment, or surgically by Heller myotomy associated with fundoplication. Esophagectomy is reserved in terminal cases (megaesophagus with dysmotility or malignancy). We present a case of achalasia that, 10 years after diagnosis, without follow-up, presented severe respiratory failure secondary to compression of the airway by the megaesophagus.

3.
Gait Posture ; 83: 147-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33152609

RESUMO

BACKGROUND: The purpose of this study was to analyse the effects of ten weeks of different running-retraining programmes on rearfoot strike (RFS) prevalence in adolescents. RESEARCH QUESTION: it is possible to change foot strike pattern in adolescents? METHODS: A total of 180 children (45.3% girls), aged 13-16 years, participated in this intervention study. The children were randomly assigned to one of three experimental groups (EGs) that each carried out a different retraining programme, based on running technique (n = 39), a 15% increased step frequency (SF) (n = 37) and barefoot training (n = 30), performed for three days each week. A control group (CG) (n = 43) did not perform any retraining. A 2D video-based analysis (240 Hz) was used to determine the RFS. RESULTS: At baseline, no significant differences in RFS prevalence were found between the EGs and the CG in either the left (χ2 = 2.048; p = 0.559) or the right foot (χ2 = 0.898; p = 0.825). In the post-test, no significant differences were found for the left foot (χ2 = 7.102; p = 0.069), but there were significant differences for the right foot (χ2 = 9.239; p = 0.025) were observed. In the re-test, no significant differences were found for either the left foot (χ2 = 2.665; p = 0.273) or the right foot (χ2 = 2.182; p = 0.325). In addition, no group displayed significant changes in RFS prevalence from the pre-test to the re-test. There was a trend towards a reduction in the RFS prevalence in both the increased SF group and the barefoot group. MEANING: The main finding of this study was that certain running-retraining programmes performed three times per week for ten weeks are not enough to modify the adolescent foot strike pattern (FSP).

4.
Chemistry ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258498

RESUMO

Donor-Acceptor Stenhouse Adducts (DASAs) are playing an outstanding role as innovative and versatile photoswitches. Until now, all the efforts have been spent on modifying donor and acceptor moieties, to modulate the absorption energy and improve the cyclization and reversion kinetics. However, there is a strong dependence on specific structural modifications and a lack of predictive behavior, mostly due to the complex photoswitching mechanism. Here, by means of a combined experimental and theoretical study, we systematically explore the effect of chemical modification of the π-bridge linking the donor and acceptor moieties, finding significant impact on the absorption, photocyclization and relative stability of the open form. Especially, a position along the π-bridge is found to be the most suited to red-shift the absorption while preserving cyclization. However, thermal back-reaction to the initial isomer is blocked. These effects are explained in terms of an increased acceptor capability offered by the π-bridge substituent that can be modulated. This strategy opens the path toward derivatives with infra-red absorption and a potential anchoring point for further functionalization.

5.
Respir Care ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293363

RESUMO

BACKGROUND: Clinical alarms play an important role in monitoring physiological parameters, vital signs and medical device function in the hospital intensive care environment. Delays in staff response to alarms are well documented as health care providers become desensitized to increased rates of nuisance alarms. Patients can be at increased risk of harm due to alarm fatigue. Current literature suggests alarms from ventilators contribute significantly to nonactionable alarms. A greater understanding of which specific ventilator alarms are most common and the rates at which they occur is fundamental to improving alarm management. METHODS: A retrospective review was performed on alarms that occurred on the Avea and Servo-i ventilators used in the pediatric ICU and pediatric cardiothoracic ICU at a major metropolitan children's hospital. High- and medium-priority alarms, as classified by the manufacturer, were studied between June 1, 2017, and November 31, 2017. Descriptive data analysis and a 2-proportion z-test were performed to identify proportionality, cause, and prevalence rates in the pediatric ICU and the cardiothoracic ICU. RESULTS: Eleven distinct ventilator alarms were identified during 2,091 d of mechanical ventilation. The Inspiratory Flow Overrange alarm (42.4%) on the Servo-i, Low VTE (20.4%; expiratory tidal volume) and Circuit Integrity alarm (20.0%) on the Avea were the most prevalent causes according to ventilator type. Medium-priority alarms comprised 68.7% of all Servo-i alarms, and high-priority alarms comprised 84% of all Avea alarms. The 2-sample test of proportions was significant for differences between both areas (P < .001). The overall alarm prevalence rate was 22.5 ventilator alarms per ventilator-day per patient. CONCLUSIONS: The cause and proportion of alarms varied by ventilator and care unit. High-priority alarms were most common with the Avea and medium-priority alarms for the Servo-i. The overall combined ventilator alarm prevalence rate was 22.5 alarms per ventilator-day per patient.

6.
Pediatr Dermatol ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222238

RESUMO

Fibroepithelial polyps are common tumors of mesodermal origin. However, only a few case reports of giant fibroepithelial polyps have been published, and they have mainly involved adults. This case report describes a 3-month-old boy with a pedunculated mass in the scrotum. To our knowledge, this is the first report of a giant congenital fibroepithelial polyp on this location.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33229221

RESUMO

BACKGROUND: CpG island methylator phenotype (CIMP) forms a distinct epigenetic phenotype in colorectal cancer (CRC). Though associated with distinct clinicopathologic characteristics, limited evidence exists of the association of CIMP with patient's reported lifestyle factors and tumor molecular characteristics. We assessed the associations of these characteristics in a pooled analysis of CRC patients. PATIENTS AND METHODS: We pooled data from 3 CRC patient cohorts: Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC), biomarker-based protocol (Integromics), and The Cancer Genome Atlas (TCGA). CIMP was measured using the classical 6-gene methylated-in-tumor (MINT) marker panel (MINT1, MINT2, MINT31, p14, p16, and MLH1) in ATTACC and genome-wide human methylation arrays in Integromics and TCGA, respectively. CIMP-High (CIMP-H) was defined as ≥ 3 of 6 methylated markers in ATTACC. In TCGA and Integromics, CIMP-H group was defined on the basis of clusters of methylation profiles and high levels of methylation in tumor samples. Baseline comparisons of characteristics across CIMP groups (CIMP-H vs. CIMP-0) were performed by Student t test or chi-square test for continuous or categorical variables, respectively. Further logistic regression analyses were performed to compute the odds ratio (OR) of these associations. RESULTS: Pooled prevalence of CIMP-H was 22% across 3 data sets. CIMP-H CRC tumors were associated with older age at diagnosis (OR, 1.02; 95% confidence interval [CI], 1.01, 1.03), microsatellite instability-high (MSI-H) status (OR, 9.15; 95% CI, 4.45, 18.81), BRAF mutation (OR, 7.70; 95% CI, 4.98, 11.87), right-sided tumor location (OR, 2.40; 95% CI, 1.78, 3.22), poor differentiation (OR, 2.94; 95% CI, 1.95, 4.45), and mucinous histology (OR, 2.47; 95% CI, 1.77, 3.47), as reported previously in the literature. CIMP-H tumors were also found to be associated with self-reported history of alcohol consumption (OR, ever vs. never, 1.58; 95% CI, 1.07, 2.34). Pathologically, CIMP-H tumors were associated with the presence of intraepithelial lymphocytes (OR, 3.31; 95% CI, 1.41, 7.80) among patients in the Integromics cohort. CONCLUSION: CIMP-H tumors were associated with history of alcohol consumption and presence of intraepithelial lymphocytes. In addition, we confirmed the previously known association of CIMP with age, MSI-H status, BRAF mutation, sidedness, and mucinous histology. Molecular pathologic epidemiology associations help us explore the underlying association of lifestyle and clinical factors with molecular subsets like CIMP and help guide cancer prevention and treatment strategies.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33052708

RESUMO

RATIONALE: Aberrant lung remodeling in idiopathic pulmonary fibrosis (IPF) is characterized by elevated MMP9 expression but the precise role of this matrix metalloproteinase in this disease has yet to be fully elucidated. METHODS: Quantitative genomic, proteomic, and functional analyses both in vitro and in vivo were used to determine MMP9 expression in IPF cells and the effects of MMP9 inhibition on profibrotic mechanisms. RESULTS: In the present study, we demonstrate that MMP9 expression was increased in airway basal-like cells (ABC-like) from IPF lungs compared with ABC cells from normal lungs. Inhibition of MMP9 activity with an anti-MMP9 antibody, andecaliximab blocked TGF-ß1-induced Smad2 phosphorylation. However, in a subset of IPF patients, TGF-ß1 activation in their ABC-like cells was unaffected or enhanced by MMP9 blockade (i.e. Non-Responders). Further analysis of Non-Responder ABC-like cells treated with andecaliximab revealed an association with the expression of type 1 IFN expression, and the addition of IFNα to these cells modulated both MMP9 expression and TGF-ß1 activation. Finally, inhibition of MMP9 ameliorated pulmonary fibrosis induced by Responder lung cells, but not a Non-Responder in a humanized immunodeficient mouse model of IPF. CONCLUSION: Together, these data demonstrate that MMP9 regulates the activation of ABC-like cells in IPF and targeting this MMP might be beneficial to a subset of IPF patients who show sufficient expression of type 1 IFNs.

9.
Arch. bronconeumol. (Ed. impr.) ; 56(10): 637-642, oct. 2020. tab, graf
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET5-2130

RESUMO

INTRODUCCIÓN: La efectividad de la punción aspiración en el tratamiento inicial del neumotórax espontáneo primario ha sido ampliamente estudiada. El objetivo de este trabajo es comparar la aspiración digital frente a la manual en un ensayo clínico aleatorizado. MÉTODOS: Se ha diseñado un ensayo clínico aleatorizado paralelo con ratio 1:1 y evaluación ciega. El ensayo clínico se adapta al estándar del grupo CONSORT. El resultado primario se define como éxito inmediato e ingreso hospitalario, y los secundarios, como recidiva, reingreso, necesidad de cirugía y días de ingreso. Se realiza encuesta de satisfacción entre los profesionales que realizan los dos tipos de punción. RESULTADOS: Sesenta y siete pacientes han sido incluidos en el estudio (n = 36 grupo control, n = 31 grupo intervención) con un seguimiento del 100%. Ambos grupos presentan un éxito inmediato del 58%, evitándose el ingreso hospitalario. No se observan diferencias en cuanto a recidiva, reingreso, necesidad de cirugía o días de ingreso. El 80% del personal que realiza la técnica de punción prefiere la aspiración digital, siendo el 100% entre el personal que realiza más de 5 punciones al año. CONCLUSIONES: Tanto la punción aspiración manual como la digital ofrecen buenos resultados inmediatos que evitan ingresos hospitalarios; la aspiración digital es el método preferido por quienes realizan dicha técnica


INTRODUCTION: The effectiveness of needle aspiration in the initial treatment of primary spontaneous pneumothorax has been widely studied. The objective of this research was to compare digital with manual aspiration in a randomized clinical trial. METHODS: We designed a blinded parallel-group randomized clinical trial with a 1:1 allocation ratio. The clinical trial is reported in line with the guidelines of the CONSORT group. The primary outcome variables were immediate success and hospital admission, while the secondary outcome measures were relapse, re-admission and need for surgery, and length of hospital stay. A satisfaction survey was also carried out among clinicians who perform these 2 types of aspiration. RESULTS: A total of 67 patients were included in the study (n = 36, control group; n = 31, experimental group) with no losses to follow-up. In both groups, 58% of procedures were immediately successful, avoiding hospital admission. No differences were found in rates of relapse, re-admission, need for surgery, or length of hospital stay. Overall, 80% of clinicians who performed aspiration preferred the digital system, and this preference rose to 100% among clinicians who performed more than 5 procedures a year. CONCLUSIONS: Both manual and digital aspiration provide good immediate results avoiding hospital admission, while digital drainage is preferred by clinicians responsible for first-line treatment of pneumothorax

10.
FASEB J ; 34(11): 14695-14709, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32959924

RESUMO

The two lysosomal integral membrane proteins MFSD1 and GLMP form a tight complex that confers protection of both interaction partners against lysosomal proteolysis. We here refined the molecular interaction of the two proteins and found that the luminal domain of GLMP alone, but not its transmembrane domain or its short cytosolic tail, conveys protection and mediates the interaction with MFSD1. Our data support the finding that the interaction is essential for the stabilization of the complex. These results are complemented by the observation that N-glycosylation of GLMP in general, but not the type of N-glycans (high-mannose-type or complex-type) or individual N-glycan chains, are essential for protection. We observed that the interaction of both proteins already starts in the endoplasmic reticulum, and quantitatively depends on each other. Both proteins can affect vice versa their intracellular trafficking to lysosomes in addition to the protection from proteolysis. Finally, we provide evidence that MFSD1 can form homodimers both in vitro and in vivo. Our data refine the complex interplay between an intimate couple of a lysosomal transporter and its accessory subunit.

11.
J Clin Med ; 9(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796717

RESUMO

We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet's disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ± SD BCVA (0.8 ± 0.3 LogMAR vs. 0.6 ± 0.3 LogMAR; p = 0.03), mean ± SD RNFL (190.5 ± 175.4 µm vs. 183.4 ± 139.5 µm; p = 0.02), mean ± SD MT (270.7 ± 23.2 µm vs. 369.6 ± 137.4 µm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10-61.5) mg/day at baseline to. 2.5 (0-5) mg/day after one year of follow-up; p = 0.001. After a mean ± SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.

12.
Medicina (Kaunas) ; 56(8)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824666

RESUMO

Background and objectives: Psoriatic arthritis (PsA) is associated with several comorbidities, including among others an increased risk of cardiovascular (CV) disease, atherosclerosis, metabolic syndrome, hypertension dyslipidemia, and diabetes. The purpose of the present study was to determine how the number of CV risk factors correlates with disease related data such as disease activity. Materials and Methods: Cross-sectional study that encompassed 305 patients who fulfilled the CASPAR criteria for PsA were assessed for lipid profile, disease activity measurements, and the presence of six traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, chronic kidney disease, and smoking status). A multivariable regression analysis, adjusted for age, sex, and disease duration, was performed to evaluate if the number of classic CV risk factors was independently related with specific features of the disease, including disease activity. Results: Disease duration was found to be higher, after adjustment for age and sex, in patients with 1 or 2, and 3 or higher CV factors, compared to those patients without CV risk factors. Similarly, DAPSA (Disease Activity in PSoriatic Arthritis score) was found to be independently upregulated in patients with a higher number of CV risk factors. In this sense, as DAPSA score increases the odds ratio (OR) of having 1 or 2 (OR 1.12 (95% confidence interval (CI) 1.03-1.21), p = 0.010), and 3 or higher (OR 1.15 (95% CI 1.04-1.26), p = 0.004) CV factors was significantly higher compared to no CV risk factors category. This was independently found after adjustment for age, sex, and disease duration. Conclusions: PsA patients with a higher number of CV risk factors exhibit an upregulated disease activity compared to those without them. This is independent of disease duration and other demographics factors.

13.
Ann Rheum Dis ; 79(12): 1544-1549, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32796045

RESUMO

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.


Assuntos
Antivirais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Imunossupressores/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Espondiloartropatias/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Fatores Etários , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Betacoronavirus , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Combinação de Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Modelos Logísticos , Lopinavir/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Polimialgia Reumática/complicações , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/epidemiologia , Prognóstico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Fatores de Risco , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais
14.
Clin Cancer Res ; 26(22): 5879-5886, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32817078

RESUMO

PURPOSE: For multiple myeloma, high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10-15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated. PATIENTS AND METHODS: In a multicenter, randomized, open-label trial, patients with multiple myeloma after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS). RESULTS: Ninety-four patients (median age, 58 years) were randomized to either arm, with 22% having International Staging System (ISS) stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high- and the low-dose arm, median PFS was 44.8 and 33.0 months (HR, 0.65; 95% CI, 0.44-0.97; P = 0.032), 36% and 23% of patients had stringent CR as best response (P = 0.08), and 4-year OS was 79% and 67% (P = 0.16), respectively. Hematologic toxicity, grade ≥3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose adjustments. SPM incidence and quality-of-life (QoL) scores in both arms were similar. CONCLUSIONS: LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent.

15.
Biochim Biophys Acta Proteins Proteom ; 1868(12): 140532, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32853771

RESUMO

Nucleophosmin (NPM1) is a mostly nucleolar protein with crucial functions in cell growth and homeostasis, including regulation of ribosome biogenesis and stress response. Such multiple activities rely on its ability to interact with nucleic acids and with hundreds of proteins, as well as on a dynamic subcellular distribution. NPM1 is thus regulated by a complex interplay between localization and interactions, further modulated by post-translational modifications. NPM1 is a homopentamer, with globular domains connected by long, intrinsically disordered linkers. This configuration allows NPM1 to engage in liquid-liquid phase separation phenomena, which could underlie a key role in nucleolar organization. Here, we will discuss NPM1 conformational and functional versatility, emphasizing its emerging, and still largely unexplored, role in DNA damage repair. Since NPM1 is altered in a subtype of acute myeloid leukaemia (AML), we will also present ongoing research on the molecular mechanisms underlying its pathogenic role and potential NPM1-targeting therapeutic strategies.


Assuntos
Reparo do DNA , Proteínas Nucleares/metabolismo , Região Organizadora do Nucléolo/genética , Região Organizadora do Nucléolo/metabolismo , Sequência de Aminoácidos , Animais , Biomarcadores , Biomarcadores Tumorais , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Imunofluorescência , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Modelos Moleculares , Terapia de Alvo Molecular , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/química , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transporte Proteico , Relação Estrutura-Atividade
16.
J Agric Food Chem ; 68(33): 8915-8924, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32683865

RESUMO

Pistachio (Pistacia vera L.) is a drought-tolerant species grown under the semiarid conditions of the Mediterranean basin. For this reason, it is essential to make an exhaustive quantification of yield and quality benefits of the kernels because the regulated deficit irrigation will allow significant water savings with a minimum impact on yield while improving kernel quality. The goal of this scientific work was to study the influence of the rootstock, water deficit during pit hardening, and kernel roasting on pistachio (P. vera, cv. Kerman) fruit yield, fruit size, and kernel content of fatty acids phytoprostanes (PhytoPs) and phytofurans (PhytoFs) for the first time. Water stress during pit hardening did not affect the pistachio yield. The kernel cultivar showed a lower oleic acid and a higher linoleic acid contents than other cultivars. Kernels from plants grafted on the studied rootstocks showed very interesting characteristics. P. integerrima led to the highest percentage of monounsaturated fatty acids. Regarding the plant oxylipins, P. terebinthus led to the highest contents of PhytoPs and PhytoFs (1260 ng/100 g and 16.2 ng/100 g, respectively). In addition, nuts from trees cultivated under intermediate water deficit during pit hardening showed increased contents of the 9-series F1-phytoprostanes and ent-16(RS)-9-epi-ST-Δ14-10-phytofuran. However, roasting of pistachios led to PhytoP degradation. Therefore, plant cultivar, deficit irrigation, rootstock, and roasting must be considered to enhance biosynthesis of these secondary metabolites. New tools using agricultural strategies to produce hydroSOS pistachios have been opened thanks to the biological properties of these prostaglandin-like compounds linking agriculture, nutrition, and food science technology for further research initiatives.

17.
Res Q Exerc Sport ; : 1-15, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669052

RESUMO

Purpose: The mechanical properties of resistance-training machines are a variable that may help to optimize sports performance and injury prevention protocols. The purpose of this study was to examine two non-gravity-dependent training modalities on muscle structure and function. Methods: Eighteen professional handball players were randomly divided into two experimental groups: 1) iso-inertial flywheel training (FW) and 2) pneumatic resistance training (PN). Participants in both groups completed twelve training sessions in six weeks consisting of three movements (lateral raise, internal and external rotation). Four sets of seven repetitions for each movement were performed during each session. Before and after training subscapularis and deltoid (anterior, middle, posterior) muscle thickness was measured. Isokinetic torque and power during internal and external rotation at 60, 180, and 240 deg·s-1 was measured as well. Throwing speed was assessed before and after training while both sitting and standing situations. Results: Both groups showed similar significant increases in throwing speed and internal and external rotation peak torque, average and peak power at all angular velocities. Anterior and middle deltoid muscle thickness changes were greater after training in FW (20 and 22%) in comparison to PN (14 and 7%, respectively). Conclusions: In summary, both flywheel and pneumatic training resulted in similar increases in shoulder strength and power and throwing speed. However, flywheel training appeared to possibly result in a slightly greater level of muscle hypertrophy of the anterior and middle deltoid. Non-gravity dependent training appears to induce changes that would be beneficial to sports performance and perhaps injury prevention.

18.
Cancer Causes Control ; 31(9): 851-860, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32666408

RESUMO

PURPOSE: Prostate cancer burden is disproportionate by race. Black men have the highest incidence and mortality rates. Rates for Hispanic men are significantly lower than for non-Hispanic Whites. Whether differences in prevalences of modifiable risk and protective factors for prostate cancer may explain these racial/ethnic differences remains unclear. METHODS: We used data from the National Health and Nutrition Examination Surveys (NHANES), which are cross-sectional and nationally representative. We selected factors known or suspected to be associated with prostate cancer and calculated risk scores combining key factors. Age-adjusted means and proportions were calculated for each factor and risk score by race/ethnicity. We estimated odds ratios (OR) using polytomous logistic regression. RESULTS: Prevalences of most factors are statistically significantly differed by race/ethnicity. In NHANES III, the prevalence of high risk score (i.e., > 25th percentile for all participants) was lower for all groups (non-Hispanic Black = 59.4%, non-US-born Mexican American = 51.4%, US-born Mexican American = 61.4%) vs. non-Hispanic White men (76.4%). Similar findings were observed for the fatal weighted risk score and for continuous NHANES. CONCLUSIONS: Our findings from this nationally representative study suggest that a combination of multiple risk and protective factors may help to explain the lower rates of prostate cancer in Mexican Americans. However, variation in these factors did not explain the higher risk of prostate cancer in non-Hispanic Black men. No one lifestyle change can reduce prostate cancer equally across all racial/ethnic groups, and modifiable factors may not explain the increased risk in black men at all. Secondary prevention strategies may provide the most benefit for black men.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Americanos Mexicanos/estatística & dados numéricos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/epidemiologia , Adulto , Estudos Transversais , Humanos , Incidência , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Prevalência , Neoplasias da Próstata/mortalidade , Fatores de Proteção , Estados Unidos/epidemiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-32646067

RESUMO

The aim of this paper is to analyze the relationships between a controlling interpersonal style, psychological need thwarting and burnout in adolescent soccer players and to test a structural equation model to analyze whether (a) a controlling interpersonal style is a predictor of psychological need thwarting and whether (b) psychological need thwarting is a predictor of burnout. A total of 103 male soccer players between the ages of 12 and 17 participated in the research (M = 14.91; SD = 5.56). The Controlling Coach Behaviors Scale, the Psychological Need Thwarting Scale, and the Athlete Burnout Questionnaire were used to evaluate the variables under study. The analyses revealed significant relationships between a controlling interpersonal style, psychological need thwarting and burnout. Furthermore, the proposed structural equations model, using the partial least squares (PLS) method, showed that a controlling style is a positive predictor of basic psychological need thwarting and that the latter is a predictor of burnout, as well as revealing an indirect relationship between a controlling style and burnout. This indirect effect of the controlling style variable on burnout can be enhanced (or attenuated) by the basic psychological need thwarting variable, which acts as a modulator.


Assuntos
Esgotamento Psicológico , Relações Interpessoais , Tutoria , Autonomia Pessoal , Satisfação Pessoal , Futebol , Adolescente , Criança , Humanos , Masculino , Inquéritos e Questionários
20.
Int J Mol Med ; 46(2): 546-560, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626972

RESUMO

Placenta­derived exosomes play an important role in cellular communication both in the mother and the fetus. Their concentration and composition are altered in several pregnancy disorders, such as gestational diabetes mellitus (GDM). The isolation and characterization of placental exosomes from serum, plasma and tissues from patients with GDM have been previously described; however, to the best of our knowledge, to date, there is no study available on placental exosomes isolated from urine of patients with GDM. In the present study, placental exosomes were purified from urine the 1st, 2nd and 3rd trimester of gestation. Placental exosomes were characterized by transmission electron microscopy in cryogenic mode and by western blot analysis, confirming the presence of exosomal vesicles. The expression profile of five microRNAs (miR­516­5p, miR­517­3p, miR­518­5p, miR­222­3p and miR­16­5p) was determined by RT­qPCR. In healthy pregnant women, the expression of the miRNAs increased across gestation, apart from miR­516­5p, which was not expressed at the 2nd trimester. All the miRNAs examined were downregulated in patients with GDM at the 3rd trimester of gestation. The downregulated miRNAs affected several metabolic pathways closely associated with the pathophysiology of GDM. This provides further evidence of the regulatory role of miRNAs in the GDM. This also suggests that the of urinary exosomes may be an excellent source of biomarkers and therapeutic targets.

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