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1.
Int J Cancer ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696517

RESUMO

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of this study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n=1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma, small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (PTWAS =1.09E-99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (PTWAS =3.72E-6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (PTWAS =6.55E-5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influence lung cancer risk. This article is protected by copyright. All rights reserved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31688926

RESUMO

BACKGROUND: Evidence indicates that socio-economic status (SES) may affect health outcomes in patients with chronic diseases. However, little is known about the impact of SES on the prognosis of acute dengue. This nationwide cohort study determined the risk of dengue haemorrhagic fever (DHF) in Taiwanese dengue fever patients from 2000 to 2014. METHODS: From 1 January 2000, we identified adult dengue cases reported in the Taiwan Centers for Disease Control Notifiable Diseases Surveillance System Database. Dengue cases were defined as positive virus isolation, nucleic acid amplification tests or serological tests. Associations between SES and incident DHF were estimated using a Cox proportional hazards model. RESULTS: Of 27 750 dengue patients, 985 (3.5%) had incident DHF during the follow-up period, including 442 (4.8%) and 543 (2.9%) with low and high SES, respectively. After adjusting for age, sex, history of dengue fever and comorbidities, low SES was significantly associated with an increased risk of incident DHF (adjusted hazard ratio [AHR] 1.61 [95% confidence interval {CI} 1.42 to 1.83]). Rural-dwelling dengue patients had a higher likelihood of DHF complication than their urban counterparts (AHR 2.18 [95% CI 1.90 to 2.51]). CONCLUSIONS: This study suggests low SES is an independent risk factor for DHF. Future dengue control programs should particularly target dengue patients with low SES for improved outcomes.

3.
J Acquir Immune Defic Syndr ; 82(5): 468-474, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31714425

RESUMO

BACKGROUND: HIV infection potentially increases coronary artery disease and heart failure risks. However, the association between HIV infection and sudden cardiac death (SCD) has not been extensively studied. This nationwide cohort study aimed to determine SCD risks in Taiwanese patients with and without HIV infection. METHODS: Adult people living with HIV/AIDS (PLWHA) since January 1, 2003, were identified from the Taiwan Centers for Disease Control HIV surveillance system. HIV-infected individuals were defined as positive HIV-1 Western blot. A control cohort without HIV infection, matched for age and sex, was selected for comparison from the Taiwan National Health Insurance Research Database. All patients were followed up until SCD, mortality for another cause, or till December 31, 2014. A time-dependent Cox proportional hazards model was used to determine the association of HIV and antiretroviral therapy (ART) with SCD. RESULTS: During a mean 5.86-year follow-up, 5342 (4.40%) of 121,530 patients (24,306 PLWHA and 97,224 matched controls) died; among them, 150 (0.12%) died of SCD. Among 150 SCD events, 97 (64.7%) and 53 (33.3%) occurred in PLWHA and controls, respectively, which corresponded to incidences of 68.31 in PLWHA and 9.31 per 100,000 person-years in controls (P < 0.001). After adjusting for age, sex, and comorbidities, HIV infection was an independent risk factor for SCD (adjusted hazard ratio, 8.15; 95% confidence interval: 5.58 to 11.90). SCD incidence was significantly lower in PLWHA receiving ART (adjusted hazard ratio 0.53; 95% confidence interval: 0.32 to 0.87). CONCLUSIONS: HIV infection is an independent risk factor for SCD. SCD rates are low in PLWHA receiving ART.

5.
J Diabetes Investig ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597015

RESUMO

AIMS/INTRODUCTION: Electronegative low-density lipoprotein (L5) is the most atherogenic fraction of low-density lipoprotein and is elevated in people with metabolic syndrome (MetS), whereas the retinol-binding protein 4 receptor (stimulated by retinoic acid 6 [STRA6]) cascade is disrupted in various organs of patients with obesity-related diseases. Our objective was to investigate whether L5 from MetS patients capably induces pathogenesis of aorta through disrupting the STRA6 cascade. MATERIAL AND METHODS: We examined the in vivo and in vitro effects of L5 on the STRA6 cascade and aortic atherogenic markers. To investigate the role of this cascade on atherosclerotic formation, crbp1 transfection was carried out in vitro. RESULTS: This study shows that L5 activates atherogenic markers (p38 mitogen-activated protein kinases, pSmad2 and matrix metallopeptidase 9) and simultaneously suppresses STRA6 signals (STRA6, cellular retinol-binding protein 1, lecithin-retinol acyltransferase, retinoic acid receptor-α and retinoid X receptor-α) in aortas of L5-injected mice and L5-treated human aortic endothelial cell lines and human aortic smooth muscle cell lines. These L5-induced changes of the STRA6 cascade and atherogenic markers were reversed in aortas of LOX1-/- mice and in LOX1 ribonucleic acid-silenced human aortic endothelial cell lines and human aortic smooth muscle cell lines. Furthermore, crbp1 gene transfection reversed the disruption of the STRA6 cascade, the phosphorylation of p38 mitogen-activated protein kinases and Smad2, and the elevation of matrix metallopeptidase 9 in L5-treated human aortic endothelial cell lines. CONCLUSIONS: This study shows that L5 from MetS patients induces atherogenic markers by disrupting STRA6 signaling. Suppression of STRA6 might be one novel pathogenesis of aorta in patients with MetS.

6.
Medicine (Baltimore) ; 98(43): e17746, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651908

RESUMO

As research progressed, the recommended duration of endocrine therapy for breast cancer patients has been extended from 5 to 10 years. This study aimed to investigate how the duration of endocrine medication and therapy affect survival rate in the real world. By using the National Health Insurance Research Database (NHIRD), this study examined 1002 breast cancer patients newly diagnosed between 2000 and 2005 as research subjects, and conducted follow-up until 2013. Among these subjects, 51 used aromatase inhibitors (AIs), 561 used tamoxifen, and 390 alternated between the use of tamoxifen and AIs. The mean follow-up period in this study was 9.63 years, and the mean duration of taking endocrine medication was 4.04 years. The tamoxifen group had the longest follow-up period (9.87 years), shortest endocrine therapy duration (3.29 years), and best survival rate (86.1%). Patients were divided into 3 groups based on the duration of endocrine therapy: under 2 years, 2 to 5 years, and over 5 years. It was found that patients who received medication for less than 2 years showed the lowest survival rate with statistically significant differences (P < .001). Therefore, the extension of endocrine therapy duration is critical in improving breast cancer patients' survival rate.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan
7.
J Dev Orig Health Dis ; : 1-8, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31581967

RESUMO

Growth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal-neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

8.
Toxicol Lett ; 318: 65-73, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654803

RESUMO

OBJECTIVE: The optimal measuring timing of serum/plasma Cystatin C (CysC) for early detection of contrast-induced acute kidney injury (CIAKI) remains un-studied. We elucidated further on this issue. METHODS: We searched PubMed, MEDLINE, and Embase from inception until March 2018 for studies evaluating diagnostic accuracy of CysC for detecting CIAKI in patients exposed to contrast agents during diagnostic examinations or cardiac/peripheral catheterizations. RESULTS: A total of 10 relevant studies, comprising 2554 patients, were included and divided into the <24 -h and 24 -h groups based on CysC measuring timing (i.e., hours after contrast agent exposure). Compared with creatinine, pooled diagnostic odds ratio of CysC for detecting CIAKI of the <24 -h and 24 -h groups was 7.59 (95 % confidence interval [CI]: 1.31-44.08) and 53.81 (95 % CI: 13.57-213.26). Pooled sensitivity of the <24 -h and 24 -h groups was 0.81 and 0.88. Pooled specificity of the <24 -h and 24 -h groups was 0.64 and 0.88, respectively. Area under the hierarchical summary receiver operating characteristic curve of the <24 -h and 24 -h groups was 0.75 and 0.93. CONCLUSIONS: Measuring CysC at 24 h after contrast agent exposure shows higher diagnostic accuracy for early detection of CIAKI than measuring CysC at <24 h after contrast agent exposure.

9.
Cancer Epidemiol ; 63: 101615, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31586822

RESUMO

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

10.
Int J Cancer ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577861

RESUMO

Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta-analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10-8 ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10-7 ; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10-7 ; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10-8 ). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.

11.
BMC Urol ; 19(1): 82, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481034

RESUMO

BACKGROUND: We aimed to investigate the prevalence, relative risk factors, and the impact on the health-related quality of life (HRQoL) of benign prostatic obstruction (BPO) with coexisting overactive bladder (OAB) in men aged over 50 and living in Shanghai Pudong New Area. METHODS: Using a multi-stage sampling and descriptive epidemiological method, 1632 men were selected from among the general population. Participants completed an evaluation of lower urinary tracts symptoms (LUTS), including international prostate symptom score (IPSS) and quality of life (QoL) questionnaires. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5) questionnaire. In addition, the Overactive Bladder Symptom Score (OABSS) and King's health questionnaire (KHQ) were used to assess the impact of BPO with coexisting OAB on the HRQoL. Maximum flow rate (Qmax), postvoid residual urine volume (PVR) and prostate-specific antigen (PSA) were also recorded. RESULTS: A total of 1476 men with complete data were analyzed. The overall prevalence of BPO with coexisting OAB was 39.6%. Age and prostate volume were associated risk factors for BPO with coexisting OAB. In addition, BPO with coexisting OAB negatively impacted the HRQoL, with increased IPSS, QoL, OABSS, and KHQ scores and decreased IIEF-5 scores compared to that in patients with BPO without OAB. CONCLUSIONS: Qmax, PVR and serum PSA did not predict whether the patients had a combined BPO + OAB or not. The prostate volume and age were associated risk factors for BPO with coexisting OAB. BPO is a progressive disease and may be one of the risk factors for OAB.

12.
BMC Public Health ; 19(1): 1215, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481039

RESUMO

BACKGROUND: To investigate the differences in body composition and metabolic syndrome (MS) under a daily 12,000-step strategy with or without moderate-intensity walking exercise in college students with obesity. METHODS: Thirty-two adults with obesity (mean (s.d.) age: 19.72 (0.80) years; height: 165.38 (3.99) cm; wt: 83.31 (4.66) kg; body mass index: 30.38 (0.83) kg m- 2) were recruited and randomly assigned to the walking step goal group (WSG; achieving 12,000 steps per day), walking exercise group (WEG; achieving 12,000 steps per day, including 3 days per week on which walking at a step rate of over 103 steps min- 1 was required), or control group (CG; maintaining a free-living life style). Each participant's accumulated daily steps from daily activities and walking exercises were monitored using a smartwatch for 8 weeks. The variables of body composition and MS were measured before and after intervention. RESULTS: Average daily steps over 8 weeks did not significantly differ between the WSG and WEG (11,677.67 (480.24) vs. 12,131.90 (527.14) steps per day, respectively, P > .05). Although the CG and WSG showed no improvement in body composition, the WEG exhibited significant improvements in terms of hip circumference and visceral fat area (VFA) (∆ - 2.28 (3.27) cm and ∆ - 13.11 (9.83) cm2, respectively, P < .05); high-density lipoprotein cholesterol (HDL-C), fasting glucose (FG), and triglycerides (TG) (∆ 16.36 (8.39), ∆ - 2.53 (3.73), and ∆ - 10.52 (36.26) mg dL- 1, respectively, P < .05). The WSG exhibited improvements only in HDL-C (∆ 14.24 (16.13) mg dL- 1, P < .05). CONCLUSION: The combination of walking exercise program and daily step goal is a more time efficient strategy in improving body composition and MS than simply establishing a daily step goal. Furthermore, this strategy may also include a potential reduction effect on the risk factors of cardiovascular diseases. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, number ACTR N12618001237279 (Retrospectively registered).

13.
Pain Physician ; 22(5): E495-E503, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561662

RESUMO

BACKGROUND: Percutaneous vertebroplasty (PVP) is now well accepted in the treatment of painful osteopathic vertebral compression fractures (OVCF), providing early pain relief and strengthening of the bone of the vertebrae. However, some patients still experienced severe back pain after PVP. OBJECTIVES: To analyze the possible reason for unsatisfactory back pain relief (UBPR) after PVP at early stage. STUDY DESIGN: Retrospective analysis. SETTING: Hong-Hui Hospital in Xi'an. METHODS: Between March 2013 and January 2015, a total of 1,316 patients with OVCF were treated by PVP at our Hospital. Demographics, clinical data, and surgical data were collected to analyze the factors associated with UBPR after PVP. RESULTS: Sixty cases complained of UBPR, and the prevalence was 4.6%. Univariate analyses showed that preoperative bone mineral density (BMD), number of fractures, cement distribution and volume injected per level, lumbodorsal fascia contusion, and depression were associated with UBPR after PVP (P < 0.001). Multivariate analysis revealed that preoperative BMD (odds ratio [OR], 3.577; P = 0.029), lumbodorsal fascia contusion (OR, 3.805; P = 0.002), number of fractures (OR, 3.440; P < 0.001), cement volume injected per level (OR, 0.079; P < 0.001), cement distribution (OR, 3.009; P = 0.013), and depression (OR, 3.426; P = 0.028) were independently associated with UBPR after PVP at the early postoperative stage. LIMITATIONS: A further prospective controlled study is needed to explore the association between the different degrees of the aforementioned factors and UBPR after PVP. CONCLUSIONS: Preoperative low BMD, lumbodorsal fascial injury, multiple segment PVP, insufficient cement injected volume, unsatisfactory cement distribution, and depression were strong risk factors associated with UBPR after PVP in patients with OVCF. KEY WORDS: Unsatisfactory back pain relief, residual back pain, percutaneous vertebroplasty.

14.
Int Heart J ; 60(5): 1168-1175, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484876

RESUMO

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.


Assuntos
Conexina 43/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Neprilisina/farmacologia , Taquicardia Ventricular/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Biópsia por Agulha , China , Modelos Animais de Doenças , Ecocardiografia/métodos , Imuno-Histoquímica , Masculino , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Taxa de Sobrevida , Sistema Nervoso Simpático/efeitos dos fármacos , Taquicardia Ventricular/diagnóstico por imagem
15.
Acta Neurol Scand ; 140(6): 414-421, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31483852

RESUMO

OBJECTIVES: To evaluate the long-term cognitive or neuropsychiatric outcomes and potential risk factors associated with prolonged cognitive deficits or neuropsychiatric symptoms in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. METHODS: In this cohort follow-up study, patients with a definitive diagnosis of anti-NMDAR encephalitis from the inpatient of West China Hospital between June 2012 and December 2017 were included and underwent a prospective cognitive and neuropsychiatric assessment every 3 months by cognitive impairment rating scale, Neuropsychiatric Inventory (NPI) and/or Montreal Cognitive Assessment. RESULTS: Up to 97.5% patients had severe cognitive deficits and neuropsychiatric symptoms in acute phase. Decreasing proportion of patients with prolonged cognitive deficits was observed and time dependent. At 2 years' follow-up, 7.8% of patients with cognitive deficits were unable to complete some previous activities or return to work. The risk factors associated with persistent cognitive deficits included age of disease onset over 40 years old (HR, 1.77; 95% CI, 1.11-2.82; P = .01) and with clinical relapses (HR, 2.22; 95% CI, 1.21-4.09; P = .02). The predictors of prolonged neuropsychiatric symptoms included clinical relapses (HR, 2.79; 95% CI, 1.21-6.43; P = .02). Among the 12 neuropsychiatric symptoms of NPI, irritability was shown as the most prevalent and persistent. CONCLUSIONS: Combined cognitive and neuropsychiatric assessment and intervention are essential elements of comprehensive care of anti-NMDAR encephalitis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31545744

RESUMO

Learning effective representations that exhibit semantic content is crucial to image retrieval applications. Recent advances in deep learning have made significant improvements in performance on a number of visual recognition tasks. Studies have also revealed that visual features extracted from a deep network learned on a large-scale image data set (e.g., ImageNet) for classification are generic and perform well on new recognition tasks in different domains. Nevertheless, when applied to image retrieval, such deep representations do not attain performance as impressive as used for classification. This is mainly because the deep features are optimized for classification rather than for the desired retrieval task. We introduce the cross-batch reference (CBR), a novel training mechanism that enables the optimization of deep networks with a retrieval criterion. With the CBR, the networks leverage both the samples in a single minibatch and the samples in the others for weight updates, enhancing the stochastic gradient descent (SGD) training by enabling interbatch information passing. This interbatch communication is implemented as a cross-batch retrieval process in which the networks are trained to maximize the mean average precision (mAP) that is a popular performance measure in retrieval. Maximizing the cross-batch mAP is equivalent to centralizing the samples relevant to each other in the feature space and separating the samples irrelevant to each other. The learned features can discriminate between relevant and irrelevant samples and thus are suitable for retrieval. To circumvent the discrete, nondifferentiable mAP maximization, we derive an approximate, differentiable lower bound that can be easily optimized in deep networks. Furthermore, the mAP loss can be used alone or with a classification loss. Experiments on several data sets demonstrate that our CBR learning provides favorable performance, validating its effectiveness.

17.
Nutrients ; 11(9)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489891

RESUMO

Alcohol consumption is a significant public health issue worldwide. The rat model and epidemiological studies have both reported conflicting results about the effects of alcohol on the kidneys. We aimed to explore the relationships between alcohol consumption and chronic kidney disease. Data from the National Health Interview Survey, the National Health Insurance research database, and the National Deaths Dataset were used. Standardized in-person interviews were executed in 2001, 2005, and 2009 to obtain the demographic characteristics of study population. The participants were followed up until 2013. The primary outcome was new-onset chronic kidney disease. We analyzed 45,200 adults older than 18 years (50.8% men and 49.2% women), and the overall mean (SD) age was 42.73 (16.64) years. During the 8.5 (3.5) years of follow-up, new-onset chronic kidney disease was recognized in 1535 (5.5%), 292 (2.7%), and 317 (4.9%) non-drinking, social-drinking, and regular-drinking participants, respectively. The participants who were social and regular drinkers had a significantly decreased risk of chronic kidney disease incidence (social drinking: adjusted hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.74-0.97; p = 0.018; regular-drinking: AHR, 0.85; 95% CI, 0.74-0.98; p = 0.024), with baseline demographics and comorbidities adjusted. In conclusion, social and regular drinkers had decreased risk of chronic kidney disease when compared with non-drinkers.

18.
Immunobiology ; 224(5): 632-637, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31402151

RESUMO

Epidemiological studies have reported that elderly patients with metabolic syndrome (MetS) are significantly more likely to develop neuronal degenerative diseases than those without MetS. Our previous study showed that patients with MetS had significantly higher levels of negatively charged very low density lipoproteins (VLDLs) in the plasma than healthy controls. Highly electronegative VLDL is a key risk factor for endothelial dysfunction and atrial fibrillation. However, the impact of negatively charged VLDL in brain immunity remains unclear. In this study, VLDLs were isolated from normal healthy (nVLDL) individuals or patients with MetS (metVLDL). Primary astroglia and microglia mixed cell cultures as well as microglial-enriched cultures were used to test the effects of VLDLs. Microglia/astroglia activation as evidenced by their morphological changes and production of pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were assessed by immunofluorescence staining and ELISA, respectively. Our results showed that metVLDLs mainly act on the microglia, and not the astroglia, with low concentration (0.05-0.5 µg/mL) inducing cell morphological changes and decreased cellular processes in the microglia. However, nVLDL treatment at these concentrations had no effects on microglia and astroglia. Most importantly, TNF-α and PGE2 levels significantly increased in the microglia treated with metVLDL via a dose-dependent manner. Together, our data indicate that metVLDLs can contribute to MetS-associated brain disorders through microglia activation and neuroinflammation.

19.
Ann Clin Transl Neurol ; 6(9): 1771-1781, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448571

RESUMO

OBJECTIVE: To explore the diversity and composition of the fecal microbiota in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: We enrolled 10 patients in the acute stage with naïve treatment, seven patients with relapse, 13 patients without relapse in the remission phase, and 12 paired healthy controls. The fecal microbiota in different groups was compared by 16S ribosomal DNA (rDNA) gene pyrosequencing. RESULTS: Prominent dysbiosis in the gut microbiome of patients with anti-NMDAR encephalitis was found. Our primary findings showed that the overall species richness (alpha diversity indexes) of the microbiota was higher in patients than in controls (P < 0.05). Distance-based community analysis revealed that the microbiota differed substantially within all subgroups of patients and controls (P < 0.05). The relative abundance of species heatmap showed a tendency toward depletion for some commensal genera, such as Prevotella_6, Bifidobacterium, Faecalibacterium, and other short-chain fatty acid (SCFA)-producing bacteria. Additionally, our results showed that all subgroups had a distinct bacterial species, with an increase in the genus Fusobacterium in the acute phase group and the genera Streptococcus and Parabacteroides in patients with relapse. However, the genus Bacteroides was very abundant in patients without relapse. Although the findings regarding the Firmicutes/Bacteroidetes (F/B) ratios across the four comparison groups were not statistically significant, the F/B ratio gradually increased in patients from the acute phase group (0.87), to the disease remission group with relapse (1.06), to the group without relapse (1.28), to the healthy group (1.63). INTERPRETATION: Patients with anti-NMDAR encephalitis exhibit a substantial alteration in fecal microbiota composition.

20.
Free Radic Biol Med ; 143: 275-287, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31442556

RESUMO

Platelet-activating factor (PAF) is a potent inflammatory agonist. In Swiss albino mice, intraperitoneal injection of PAF causes sudden death with oxidative stress and disseminated intravascular coagulation (DIC), characterized by prolonged prothrombin time, thrombocytopenia, reduced fibrinogen content, and increased levels of fibrinogen degradation products. However, the underlying mechanism(s) is unknown. The PAF-R antagonist WEB-2086 protected mice against PAF-induced death by reducing DIC and oxidative stress. Accordingly, general antioxidants such as ascorbic acid, α-tocopherol, gallic acid, and N-acetylcysteine partially protected mice from PAF-induced death. N-acetylcysteine, a clinically used antioxidant, prevented death in 67% of mice, ameliorated DIC characteristics and histological alterations in the liver, and reduced oxidative stress. WEB-2086 suppressed H2O2-mediated oxidative stress in isolated mouse peritoneal macrophages, suggesting that PAF signaling may be a downstream effector of reactive oxygen species generation. PAF stimulated all three (ERK, JNK, and p38) of the MAP-kinases, which were also inhibited by N-acetylcysteine. Furthermore, a JNK inhibitor (SP600125) and ERK inhibitor (SCH772984) partially protected mice against PAF-induced death, whereas a p38 MAP-kinase inhibitor (SB203580) provided complete protection against DIC and death. In human platelets, which have the canonical PAF-R and functional MAP-kinases, JNK and p38 inhibitors abolished PAF-induced platelet aggregation, but the ERK inhibitor was ineffective. Our studies identify p38 MAP-kinase as a critical, but unrecognized component in PAF-induced mortality in mice. These findings suggest an alternative therapeutic strategy to address PAF-mediated pathogenicity, which plays a role in a broad range of inflammatory diseases.

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