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1.
Artigo em Inglês | MEDLINE | ID: mdl-35514254

RESUMO

The bioequivalence of the reference and test linagliptin formulations was assessed in healthy Chinese subjects under fasting and fed conditions. The study was designed as a single-dose, randomized, open-label, 2-period crossover study with a 35-day washout period between 2 administrations. Forty-eight healthy subjects received 5 mg of test and reference linagliptin formulation orally under fasting condition. The geometric mean of the maximum observed linagliptin concentration (Cmax ) for the test formulation was 4.9 ng/mL (reference, 5.0 ng/mL), the area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72 ) was 154.7 ng · h/mL (reference, 157.4 ng · h/mL). Thirty-six subjects received 5 mg of test and reference linagliptin formulation orally under fed conditions. The geometric mean of Cmax for the test linagliptin formulation was 2.8 ng/mL (reference, 2.8 ng/mL), AUC0-72 was 133.5 ng · h/mL (reference, 136.6 ng · h/mL). The 90%CIs for the test/reference ratio for Cmax and AUC0-72 met the bioequivalence criteria (80%-125%). The test and reference formulations of linagliptin were well tolerated and bioequivalent under fasting and fed conditions.

2.
Ann Transl Med ; 10(8): 477, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571398

RESUMO

Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic. Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.AG) (n=20), middle age group (age from 45 to 65 years) (M.AG) (n=13) 45-65 years, and older age group (age >65 years) (O.AG) (n=20). The relationships between gut microbiota and different ages were explored using 16S rRNA gene sequencing data. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fisher's exact and Mann-Whitney U-test were used for the data analysis. Results: Pairwise comparison between the three groups showed that the α-diversity of Y.AG was significantly higher than that of O.AG (ACE Index, P=0.017; chao1 Index, P=0.031; observed_species Index, P=0.011; and goods_coverage Index, P=0.041). The ß-diversity in the 3 groups differed significantly (stress =0.100), while the composition (ß-diversity) differed significantly between the Y.AG and the M.AG (stress =0.090), the M.AG and the O.AG (stress =0.095), and the Y.AG and the O.AG (stress =0.099). At the genus level, 7 bacterial genera were significantly enriched in the O.AG compared with the Y.AG, of which Streptococcus, Blautia, Erysipelotrichaceae_UCG-003, and Fusicatenibacter represented the major variances in O.AG microbiomes. Eleven genera were significantly increased in the O.AG, of which Prevotella, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Ruminiclostridium, and Phascolarctobacterium represented the major variances in the O.AG. The Y.AG and the O.AG were predicted by PICRUSt2 analysis, which found 72 pathways related to differential gut microbiome at the genus level. Redundancy analysis showed that 7 environmental factors were significantly correlated with intestinal microorganisms, especially in the Y.AG compared with the O.AG. Conclusions: Analysis of gut microbiota characteristics in patients of different ages could ultimately contribute to the development of novel avenues for the treatment of HCC at different ages.

3.
Eur J Pharm Sci ; 173: 106180, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35378210

RESUMO

OBJECTIVE: Gout is a widespread inflammatory arthritis. The present study aimed to identify potential biomarkers of gout and explore their underlying mechanisms through bioinformatics methods. METHODS: The microarray data was downloaded from the GSE160170 dataset from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to obtain differentially expressed genes (DEGs). We searched for gout-related genes through the DisGeNET and GeneCards databases, and the final DEGs was acquired by intersection with the DEGs obtained from the microarray dataset. Tissue- and organ-specific genes were identified by the BioGPS online tool. Enrichment analysis was performed using GSEA4.1.0 and KOBAS3.0, and a protein-protein interaction (PPI) network was constructed using STRING to understand the biological functions and enrichment pathways of the DEGs as well as to identify their hub genes. Cytoscape was used to construct the competitive endogenous RNA (ceRNA) networks. RESULTS: A total of 653 differentially expressed lncRNAs (DElncRNAs) and 818 differentially expressed mRNAs (DEmRNAs) were identified in the present study. After intersecting the differential DEGs from the dataset, 85 DEGs were obtained. Enrichment analyses showed that the DEGs were mainly enriched in the following biological processes (BPs): inflammation and regulation; immune response; and cell proliferation and apoptosis. Moreover, the DEGs were mainly enriched in rheumatoid arthritis (RA), osteoclast differentiation, interleukin (IL)-17 signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, Toll-like receptor signaling pathway and tumor necrosis factor (TNF) signaling pathway. Cytoscape software identified 15 hub genes, and the following 9 hub genes were obtained after intersecting with genes specifically expressed in the blood/immune and bone/muscle systems: TNF, JUN, PTGS2, STAT1, IL6, FOS, IL1ß, CXCL8 and CD80. In addition, the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a key regulatory pathway in the pathogenesis of gout. CONCLUSIONS: The present study indicated that the identified 9 hub genes may be potential biomarkers for the diagnosis and treatment of gout. In addition, the results suggested that the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a potential RNA regulatory pathway that controls the progression of gout disease.


Assuntos
Gota , MicroRNAs , RNA Longo não Codificante , Biomarcadores/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Gota/diagnóstico , Gota/genética , Humanos , Interleucina-6 , MicroRNAs/genética
4.
Front Cardiovasc Med ; 9: 827491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402571

RESUMO

Background: Birth weight has been reported to be associated with the risk of incident cardiovascular disease (CVD); however, the relationship remains inconclusive. Here, we aimed to prospectively assess the associations between birth weight and CVD risk using the data from UK Biobank, a large-scale, prospective cohort study. Methods: We included 270,297 participants who were free of CVD at baseline and reported their birth weight for analyses. The primary outcome was incident CVD. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using Cox proportional hazards models adjusted for potential confounding variables. Results: During a median follow-up of 8.07 years (IQR: 7.4-8.7 years), 10,719 incident CVD events were recorded. The HRs for low birth weight vs. normal birth weight (2.5-4.0 kg) were 1.23 (95% CI: 1.09-1.38) for risk of incident CVD, 1.52 (95% CI: 1.18-1.95) for stroke, 1.33 (95% CI: 1.07-1.64) for myocardial infarction, and 1.15 (95% CI: 1.01-1.32) for CHD. For the ones with low birth weight, the risk of CVD is reduced by 11% for every kilogram of birth weight gain. The association of low birth weight with CVD was stronger among those younger than 55 years (p = 0.001). No association between high birth weight and risk of cardiovascular outcomes was found. Conclusion: Low birth weight was associated with an increased risk of cardiovascular events. These findings highlight the longstanding consequence of low birth weight on cardiovascular system.

5.
J Pers Med ; 12(4)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35455649

RESUMO

Precision nutrition is an emerging area of nutrition research, with primary focus on the individual variability in response to dietary and lifestyle factors, which are mainly determined by an individual's intrinsic variations, such as those in genome, epigenome, and gut microbiome. The current research on precision nutrition is heavily focused on genome and gut microbiome, while epigenome (DNA methylation, non-coding RNAs, and histone modification) is largely neglected. The epigenome acts as the interface between the human genome and environmental stressors, including diets and lifestyle. Increasing evidence has suggested that epigenetic modifications, particularly DNA methylation, may determine the individual variability in metabolic health and response to dietary and lifestyle factors and, therefore, hold great promise in discovering novel markers for precision nutrition and potential targets for precision interventions. This review summarized recent studies on DNA methylation with obesity, diabetes, and cardiovascular disease, with more emphasis put in the relations of DNA methylation with nutrition and diet/lifestyle interventions. We also briefly reviewed other epigenetic events, such as non-coding RNAs, in relation to human health and nutrition, and discussed the potential role of epigenetics in the precision nutrition research.

6.
Nat Prod Res ; : 1-7, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476591

RESUMO

A new withanolide, talasteroid (1), and a known steroid (2), along with eight meroterpenoids (3-10), were obtained from the rice culture of the marine-derived fungus Talaromyces stollii HBU-115. The structure of 1 including its absolute configuration was determined by extensive 1 D and 2 D NMR spectroscopy, and single-crystal X-ray diffraction analysis. Compound 1 represents the first withanolide featuring a 4-substituted 2,3-dimethyl-2-butenolide ring in the side chain. The isolated compounds were evaluated for their antimicrobial and antioxidant activities.

7.
Pain Res Manag ; 2022: 7570533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463630

RESUMO

Objective: This meta-analysis aims to evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in treating post-operative pain. Methods: This meta-analysis was registered in PROSPERO (CRD42021286753). We searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs) about TEAS in treating postoperative pain that were published before November 2021. The primary outcome was visual analogue scale (VAS) within 24 h after surgery. The secondary outcomes included postoperative opioid analgesic drug consumption and the occurrence of adverse reactions within the postoperative 24-72 h. Adverse reactions included dizziness, nausea, and vomiting. Continuous variables were analyzed using mean difference (MDs) or standardized mean difference (SMDs) and 95% CIs. Relative risk (RR) and 95% CI were used for dichotomous data. The data were pooled and analyzed by RevMan 5.4 and STATA15.0 software. Results: Seventeen trials with 1375 participants were included. The current results suggested that application of TEAS showed obvious superiority in reducing VAS scores (SMD = -1.51, 95% CI = -2.20∼-0.82, I2 = 96%). Subgroup analysis was performed according to open surgery and minimally invasive surgery. VAS scores were decreased after surgery at 24 h (SMD = -0.84, 95% CI = -1.07∼-0.6, I2 = 96%; SMD = -0.88, 95% CI = -1.02∼-0.75, I2 = 96%). The incidence of postoperative dizziness and nausea and vomiting was significantly lower in the TEAS group within postoperative 24-72 h (RR = 0.48, 95% CI = 0.34∼0.68, I2 = 0%; RR = 0.66, 95% CI = 0.44∼1.01, I2 = 69%; and RR = 0.49, 95% CI = 0.24∼1.00, I2 = 51%). Postoperative opioid analgesics were also reduced in the TEAS group within 72 h after surgery (SMD = -2.10, 95% CI = -3.37∼-0.82, I2 = 96%). Conclusions: TEAS can reduce postoperative pain as well as the incidence of dizziness, nausea, and vomiting and the number of analgesics used after surgery. TEAS is a reasonable modality to incorporate into a multimodal management approach for postoperative pain.


Assuntos
Pontos de Acupuntura , Tontura , Analgésicos Opioides/uso terapêutico , Tontura/complicações , Tontura/tratamento farmacológico , Humanos , Náusea , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito
8.
Artigo em Inglês | MEDLINE | ID: mdl-35412974

RESUMO

Data augmentation is a critical technique in object detection, especially the augmentations targeting at scale invariance training. However, there has been little systematic investigation of how to design scale-aware data augmentation for object detection. We propose Scale-aware AutoAug to learn data augmentation policies for object detection. We define a new scale-aware search space, where both image- and instance-level augmentations are designed for maintaining scale robust feature learning. Upon this search space, we propose a new search metric, to facilitate efficient augmentation policy search. In experiments, Scale-aware AutoAug yields significant and consistent improvement on various object detectors, even compared with strong multi-scale training baselines. Our searched augmentation policies are generalized well to other datasets and instance segmentation. The search cost is much less than previous automated augmentation approaches for object detection. Based on the searched scale-aware augmentation policies, we further introduce a dynamic training paradigm to adaptively determine specific augmentation policy usage during training. The dynamic paradigm consists of an heuristic manner for image-level augmentations and a differentiable method for instance-level augmentations. The dynamic paradigm achieves further performance improvements to Scale-aware AutoAug without any additional burden on the long tailed LVIS benchmarks and large Swin Transformer models.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35399636

RESUMO

Background: Well known for its good anti-inflammatory effect, curcuma longa extract (CLE)/curcumin (C) has a potential effect on osteoarthritis (OA), and a large number of researchers have completed several systematic reviews/meta-analyses (SRs/MAs) in this research area. However, the methodological and evidentiary quality of these SRs/MAs need to be further evaluated, and whether these findings provide reliable evidence for clinicians remains controversial. Methods: Two researchers collected data from seven databases for SRs/MAs that are about randomized controlled trials (RCTs) on CLE/C for OA. Assessment was made for the SRs/MAs included in this article by means of the Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Nine published SRs/MAs were included in our study. According to the results of the AMSTAR-2 assessment, only one SR/MA was assessed as high quality. According to the ROBIS evaluation results, only 2 SRs/MAs have a low risk of bias. According to the results of the PRISMA checklist assessment, only 2 SRs/MAs studies fully reported the checklist, while other studies had reporting flaws. According to GRADE, a total of 59 effect sizes extracted from the included SRs/MAs were evaluated, among which no effect size was rated as high. Conclusions: CLE/C may be an effective and safe complementary treatment for OA. However, further standard SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this.

10.
Future Oncol ; 18(17): 2113-2125, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35266821

RESUMO

Aim: To assess whether Ki67 is related to the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in hepatocellular carcinoma patients at high risk of postsurgical recurrence. Methods: A total of 716 patients undergoing surgical resection with or without PA-TACE were retrospectively enrolled. Immunohistochemistry was used to analyze Ki67 expression. Results: There was no significant difference in tumor-free survival between patients who underwent resection with or without chemoembolization. However, chemoembolization was associated with significantly higher tumor-free survival rates among patients with 'low' (<30%) or 'moderate' (30-59%) levels of Ki67. Patients highly expressing Ki67 displayed higher rates of overall recurrence, earlier recurrence, multiple intrahepatic recurrence and extrahepatic metastasis. Conclusion: In patients with relatively high Ki67 levels, PA-TACE does not appear to improve outcomes.


Postoperative adjuvant transarterial chemoembolization (PA-TACE), as an adjuvant treatment to surgery, is widely recommended in patients with high-risk factors for recurrence. Nevertheless, some studies challenge whether it actually improves prognosis, thus the influence of PA-TACE on prognosis remains controversial. The present research indicated that the ability of PA-TACE to help inhibit hepatocellular carcinoma recurrence is conditionally restrictive, and it appears to be beneficial only in those patients with a low or moderate Ki67 index (<60%). For patients with high Ki67 expression, compared with PA-TACE, 'adjuvant immunotherapy' may be a potential alternative option. This finding suggests a valuable reference to identify the best beneficiaries of PA-TACE for individualized treatment.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia , Humanos , Antígeno Ki-67 , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
11.
Geroscience ; 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35306636

RESUMO

We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60 years old. A total of 174,161 participants were free of dementia at baseline. The APOE ε4-related genetic risk was evaluated by the number of APOE ε4 alleles. The overall genetic susceptibility of dementia was evaluated by polygenetic risk score (PRS). Cox proportional hazards models were used to estimate the association between educational attainment and incident dementia. During a median of 8.9 years of follow-up, a total of 1482 incident cases of dementia were documented. After adjustment for covariates, we found that low education attainment was significantly associated with higher dementia risk in the APOE ε4 carriers, and such relation appeared to be stronger with the increasing number of ε4 alleles. In contrast, educational attainment was not associated with dementia risk in non-APOE ε4 carriers (P for multiplicative interaction = 0.006). In addition, we observed that the dementia risk associated with a combination of low educational attainment and high APOE ε4-related genetic risk was more than the addition of the risk associated with each of these factors (P for additive interaction < 0.001). We found similar significant interactions between educational attainment and PRS on both the multiplicative and additive scales on the dementia risk, mainly driven by the APOE genotype. These data indicate that higher educational attainment in early life may attenuate the risk for dementia, particularly among people with high genetic predisposition.

13.
Chem Soc Rev ; 51(7): 2681-2709, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35253033

RESUMO

As a new member of carbon allotropes, graphdiyne (GDY) has the characteristics of being one-atom-thick with two-dimensional layers comprising sp and sp2 hybridized carbon atoms, and represents a trend in the development of carbon materials. Its unique chemical and electronic structures give GDY many unique and fascinating properties such as rich chemical bonds, highly conjugated and super-large π structures, infinitely distributed pores and high inhomogeneity of charge distribution. GDY has entered a period of rapid development, especially with the significant emergence of fundamental research and applied research achievements over the past five years. As one of the frontiers of chemistry and materials science, graphdiyne was listed in the Top 10 research areas in the 2020 Research Frontiers report and was jointly released in the Top 10 in the world by Clarivate and the Chinese Academy of Sciences. The research results have shown the great potential of GDY in the applications of energy, catalysis, environmental science, electronic devices, detectors, biomedicine and therapy, etc. Scientists are eager to explore and fully reveal the new properties, discover new scientific concepts and phenomena, discover the new conversion modes and mechanisms of GDY in photoelectricity, energy, and catalysis, etc., and build the important scientific value of new conversion devices. This review covers research on the foundation and application of GDY, such as the controlled preparation of new methods of GDY and GDY-based materials, studies on new mechanisms and properties in chemistry and physics, and the foundation and applications in energy, catalysis, photoelectric and devices.


Assuntos
Carbono , Grafite , Carbono/química , Catálise , Eletrônica , Grafite/química
14.
Am J Clin Nutr ; 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35348584

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs and important post-transcriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. OBJECTIVES: We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. DESIGN: This study included adults with abdominal obesity from an 18-month diet and physical activity intervention trial. Circulating levels of miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 months; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal (visceral [VAT], deep subcutaneous [DSAT], superficial subcutaneous [SSAT]) adipose tissue (cm2) (n = 144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n = 141) and pancreas (n = 143). RESULTS: Greater decreases in miR-100-5p were associated with more reductions of VAT (ß per 1 SD decrease: -9.63 [SE 3.13]; P = 0.0025], DSAT (ß -5.48 [2.36]; P = 0.0218), SSAT (ß -4.64 [1.68]; P = 0.0067), and intrahepatic fat percentage (ß -1.54 [0.49]; P = 0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-month reductions of VAT (ß -10.12 [3.31] per 1 SD decrease; P = 0.0027) and intrahepatic fat percentage (ß -1.28 [0.52]; P = 0.015). Further, decreases in circulating miR-99b-5p (ß per 1 SD decrease: -0.44 [0.21]; P = 0.038) and miR-100-5p (ß -0.50 [0.23]; P = 0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 months. CONCLUSIONS: Decreases in circulating miR-99-5p/100-5p levels induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity.

15.
J Gastrointest Oncol ; 13(1): 326-343, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284109

RESUMO

Background: This study sought to evaluate the association between intestinal Klebsiella and post-hepatectomy liver failure (PHLF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (B-HCC), and identify the inner relationship. Methods: Patients with B-HCC were divided into Groups A and B based on the presence or absence of PHLF. 16S ribosomal ribonucleic acid surveys were used to identify gut microbiome alterations. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fecal and serum samples were processed by chromatography-mass spectrometry based non-targeted metabonomics, then comprehensively analyzed to obtain hub metabolites. A Spearman correlation analysis was then conducted to find any associations between fecal differential metabolites and the relative abundance of differential microbes. Results: Hepatectomies were significantly associated with a gut microbial imbalance in B-HCC patients, and a significant elevation of Klebsiella abundance was observed in PHLF patients. Klebsiella appears to act on 13 amino acid-related pathways, especially significantly observed in branched-chain amino acid (BCAA) metabolic pathways. Additionally, Klebsiella was found to be highly correlated with 3-methyl-2-oxobutanoic acid shared by feces and serum in the BCAA metabolic pathway. Conclusions: Hepatectomy can lead to an imbalance of intestinal microflora in B-HCC patients. Due to its potential connections with 3-methyl-2-oxobutanoic acid in the BCAA pathway, significantly increased Klebsiella has the potential to be an evaluation indicator of PHLF in B-HCC patients. Moreover, 3-methyl-2-oxobutanoic acid has research value in PHLF-targeted treatments.

16.
Diabetes Obes Metab ; 24(6): 1000-1009, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35112774

RESUMO

AIMS: To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions. METHODS: This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight-loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual-energy X-ray absorptiometry and computed tomography scans at baseline, 6 months and 24 months. RESULTS: From baseline to 6 months, when the maximum weight loss was achieved, each 1000-steps/d increment in PA was associated with a greater reduction in body weight (ß[SE] = -0.48[0.11]) and waist circumference (ß[SE] = -0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rate qvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24-month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6 months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P∆PA*diet < 0.05). CONCLUSIONS: Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight-loss diets, and such associations were more evident in people on a high-fat or average-protein diet compared with a low-fat or high-protein diet.


Assuntos
Actigrafia , Perda de Peso , Composição Corporal , Dieta Redutora , Exercício Físico , Humanos , Obesidade/metabolismo
17.
Mayo Clin Proc ; 97(3): 519-530, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35135690

RESUMO

OBJECTIVE: To prospectively assess whether sleep patterns modified lifestyle-associated cardiovascular disease (CVD) risk. PATIENTS AND METHODS: This study included 393,690 participants without CVD at baseline measurements between March 13, 2006, and October 1, 2010, from UK Biobank. A lifestyle score was calculated on the basis of the 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet), and sleep patterns were constructed based on sleep duration, chronotype, insomnia, snoring, and daytime dozing. RESULTS: During a median follow-up of 8.93 years, we observed 10,218 incident CVD events, including 6595 myocardial infarctions (MIs) and 3906 strokes. We found that sleep patterns significantly modified the relations of the lifestyle score with incident CVD (P for interaction =.007) and MI (P for interaction =.004). Among participants with a poor sleep pattern, unfavorable lifestyle (per score increase) was associated with 25% (95% CI, 13% to 39%) and 29% (95% CI, 13% to 47%) increased risks for CVD and MI, while among participants with a healthy sleep pattern, unfavorable lifestyle was associated with 18% (95% CI, 15% to 21%) and 17% (95% CI, 13% to 21%) increased risks for CVD and MI. CONCLUSION: Our results indicate that adherence to a healthy sleep pattern may attenuate the CVD risk associated with an unfavorable lifestyle.


Assuntos
Doenças Cardiovasculares , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Estilo de Vida , Estudos Prospectivos , Fatores de Risco , Sono
18.
Int Immunopharmacol ; 106: 108599, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35193054

RESUMO

We aimed to compare the pharmacokinetics, safety, and immunogenicity of the adalimumab biosimilar SCT630 with those of its reference (adalimumab, Humira®). This study involved a randomized, double-blind, parallel-controlled design; healthy subjects (N = 146) were randomly distributed into two groups to receive a single-dose subcutaneous injection of 40 mg SCT630 or 40 mg adalimumab, with a 71-day follow up. The bioequivalence of the primary pharmacokinetic parameters (AUC0-t) and maximum observed serum concentration (Cmax) between SCT630 and adalimumab were the primary endpoints; safety and immunogenicity of SCT630 compared with those of adalimumab were the secondary endpoints. The geometric mean Cmax ratio of SCT630 to adalimumab and its 90% confidence interval (CI) were 116.02% and 108.66%-123.88%, AUC0-t ratio and 90% CI were 109.47% and 99.80%-120.08%, and AUC0-∞ ratio and 90% CI were 109.24% and 99.80%-120.78%. These PK parameters fulfilled the equivalence criterion of 80.00%-125.00%. Treatment-emergent adverse events (TEAEs) occurred in 62 (84.9%) and 61 (83.6%) subjects; mild and moderate drug-related TEAEs were observed in 60 (82.2%) and 59 (80.8%) subjects in the adalimumab and SCT630 groups, respectively. On day 71, 69 (95.8%) subjects in the adalimumab group and 66 (93%) in the SCT630 group reported positive anti-drug antibodies. Among them, 15 (21.7%) and 11 (16.7%) subjects showed positive neutralizing antibodies, with no significant difference. SCT630 was well tolerated and demonstrated PK and safety profiles similar to adalimumab. The profiles support the initiation of further confirmatory study to demonstrate the clinical similarity of SCT630 to adalimumab.


Assuntos
Medicamentos Biossimilares , Adalimumab/efeitos adversos , Área Sob a Curva , Medicamentos Biossimilares/efeitos adversos , China , Método Duplo-Cego , Voluntários Saudáveis , Humanos
19.
Diabetes ; 71(5): 934-944, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202470

RESUMO

To examine associations between sleep disturbance and changes in weight and body composition and the mediating role of changes of appetite and food cravings in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) 2-year weight-loss diet intervention trial, this study included 810 overweight or obese individuals with baseline sleep disturbance assessment who were randomly assigned one of four diets varying in macronutrient composition. Changes in body weight and fat distribution were assessed by DEXA and computed tomography during the 2-year intervention. Participants were asked to provide sleep disturbance levels (no, slight, moderate, or great) at baseline and to recall their sleep disturbances since last visit at 6, 12, 18, and 24 months. Weight loss during the first 6 months was followed by 1.5 years of steady weight regain. Participants with greater sleep disturbance from baseline to 6 months showed significant losses of body weight (Ptrend <0.001) and waist circumference (Ptrend = 0.002) at 6 months, after multivariate adjustment. Compared with individuals without sleep disturbance at all from baseline to 6 months, those with slight, moderate, or great sleep disturbance showed an elevated risk of failure to lose weight (-5% or more loss) at 6 months, when the maximum weight loss was achieved, with an odds ratio of 1.24 (95% CI 0.87, 1.78), 1.27 (95% CI 0.75, 2.13), or 3.12 (95% CI 1.61, 6.03), respectively. In addition, we observed that the repeatedly measured levels of sleep disturbance over 2 years were inversely associated with the overall weight loss rate (weight changes per 6 months) (Ptrend <0.001). Further, sleep disturbances during weight loss from baseline to 6 months and weight regain from 6 months to 24 months were significantly predictive of total fat, total fat mass percent, and trunk fat percent changes during the 2 years. Our results also indicated that food cravings for carbohydrates/starches, fast food fats, and sweets; cravings, prospective consumption, hunger of appetite measurements; and dietary restraint, disinhibition, and hunger subscales measured at 6 months significantly mediated the effects of sleep disturbance on weight loss. In conclusion, our results suggested that more severe sleep disturbance during weight loss was associated with an elevated risk of failure to lose weight during the dietary intervention. Food cravings and eating behaviors may partly mediate these associations.


Assuntos
Sobrepeso , Perda de Peso , Composição Corporal , Índice de Massa Corporal , Dieta Redutora/métodos , Ingestão de Energia , Humanos , Estudos Prospectivos , Sono , Ganho de Peso , Perda de Peso/fisiologia
20.
Clin Nutr ; 41(3): 731-736, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35172255

RESUMO

BACKGROUNDS &AIMS: Previous studies have shown that marine omega-3 PUFAs (fish oil) supplements was associated with improved cognitive function, whereas the association between use of fish oil supplements and risk of incident dementia was still unclear. We aimed to prospectively assess the relations between use of fish oil supplements and risks of all-cause and disease-specific dementia according to the apolipoprotein E (APOE) ε4 dosage. METHODS: A total of 445,961 participants from UK biobank, who were free of dementia at baseline and completed data on supplement use and genetic information were analyzed in this study. Cox proportional hazards models were used to calculate the hazard ratios (HRs) comparing incident dementia rates in participants who did and did not use fish oil. RESULTS: During a median of 12.2 years of follow-up, a total of 5795 incident cases of dementia were documented, including 1266 cases of vascular dementia and 2382 cases of AD. After adjustment for covariates, use of fish oil supplements was significantly associated with lower risks of all-cause dementia (Hazard ratios, HR, 95% CI, 0.90, 0.85-0.96) and vascular dementia (HR, 0.85; 95% CI, 0.75-0.97), but not AD (HR, 0.99; 95% CI, 0.91-1.09). For all-cause dementia and vascular dementia, we found that the protective associations appeared to be attenuated by the increasing APOE ε4 dosage (P-interaction = 0.002 and 0.002, respectively). Notably, the use of fish oil supplements was significantly associated with an 86.0% higher risk of vascular dementia in participants with two APOE-ε4 alleles (HR, 1.86, 95%CI, 1.23-2.80). CONCLUSIONS: Our results indicate that use of fish oil supplements is differently associated with risks of all-cause dementia and vascular dementia according to the APOE ε4 dosage.


Assuntos
Apolipoproteína E4 , Demência Vascular , Apolipoproteína E4/genética , Demência Vascular/epidemiologia , Demência Vascular/genética , Demência Vascular/prevenção & controle , Óleos de Peixe , Genótipo , Humanos , Incidência , Fatores de Risco
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