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1.
Am J Surg ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31575418

RESUMO

BACKGROUND: Trauma prediction scores such as Revised Trauma Score (RTS) and Trauma and Injury Severity Score (TRISS)) are used to predict mortality, but do not include comorbidities. We analyzed the American Society of Anesthesiologists physical status (ASA PS) for predicting mortality in trauma patients undergoing surgery. METHODS: This multicenter, retrospective study compared the mortality predictive ability of ASA PS, RTS, Injury Severity Score (ISS), and TRISS using a complete case analysis with mixed effects logistic regression. Associations with mortality and AROC were calculated for each measure alone and tested for differences using chi-square. RESULTS: Of 3,042 patients, 230 (8%) died. The AROC for mortality for TRISS was 0.938 (95%CI 0.921, 0.954), RTS 0.845 (95%CI 0.815, 0.875), and ASA PS 0.886 (95%CI 0.864, 0.908). ASA PS + TRISS did not improve mortality predictive ability (p = 0.18). CONCLUSIONS: ASA PS was a good predictor of mortality in trauma patients, although combined with TRISS it did not improve predictive ability.

2.
Phys Rev Lett ; 123(7): 073601, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31491088

RESUMO

Higher-order topological insulators and superconductors are topological phases that exhibit novel boundary states on corners or hinges. Recent experimental advances in controlling dissipation such as gain and loss in atomic and optical systems provide a powerful tool for exploring non-Hermitian topological phases. Here we show that higher-order topological corner states can emerge by introducing staggered on-site gain and loss to a Hermitian system in a trivial phase. For such a non-Hermitian system, we establish a general bulk-corner correspondence by developing a biorthogonal nested-Wilson-loop and edge-polarization theory, which can be applied to a wide class of non-Hermitian systems with higher-order topological orders. The theory gives rise to topological invariants characterizing the non-Hermitian topological multipole moments (i.e., corner states) that are protected by reflection or chiral symmetry. Such gain- and loss-induced higher-order topological corner states can be experimentally realized using photons in coupled cavities or cold atoms in optical lattices.

4.
Inorg Chem ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532643

RESUMO

A three-dimensional polymolybdate-based metal-organic framework (POMOF) consisting of Zn-ε-Keggin unit and organic linker, {[PMo8VMo4VIO37(OH)3Zn4][BPE]2}·[BPE] (1), was successfully obtained by the hydrothermal method. Compound 1 is composed of Zn-ε-Keggin units and BPE ligands, featuring a fascinating 5-fold interpenetrating framework with dia topology. The catalytic performance of compound 1 was investigated, and experiments showed that 1 could effectively facilitate the cycloaddition reaction of CO2 with epoxides as Lewis acid heterogeneous catalyst. Moreover, compound 1 also was studied as LIBs anode material, and it showed reversible capacity of 546 mA h g-1 at 100th cycle.

5.
Inorg Chem ; 58(16): 10883-10889, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31390180

RESUMO

Two novel and fascinating high-nuclearity lanthanide-transition (4f-3d) heterometallic clusters were obtained based on an anion-template (Cl-) and ligand-controlled approach, formulated as [Gd40Ni44(CO3)12(CH3COO)4(IDA)44(C2O4)(µ2-O)4(µ3-OH)60(µ3-O)6(H2O)12]·Cl10·20H2O (abbreviated as Gd40Ni44, 1) and [Eu40Ni44(CO3)12(CH3COO)6(IDA)44(C2O4)(µ2-O)4(µ3-OH)62(µ3-O)4(H2O)12]·Cl10·23H2O (abbreviated as Eu40Ni44, 2), where H2IDA = iminodiacetic acid and H2C2O4 = oxalic acid. Structural analysis exhibits that the compounds 1 and 2 were both constructed by two enticing bowl-like anion units Ln20Ni22, featuring peanut-like structures. Besides, the assembly of Ln20Ni22 was templated by five Cl- ions. Magnetically, compound 1 shows a significant magnetocaloric effect, with -ΔSm = 36.05 J kg-1 K-1 at 3 K for ΔH = 7 T.

6.
Theranostics ; 9(16): 4688-4703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367250

RESUMO

Deciphering the molecular and cellular processes involved in foam cell formation is critical to understanding the pathogenesis of atherosclerosis. Interferon regulatory factor 1 (IRF1) was first identified as a transcriptional regulator of type-I interferons (IFNs) and IFN inducible genes. Our study aims to explore the role of IRF1 in atherosclerotic foam cell formation and understand the functional diversity of IRF1 in various cell types contributing to atherosclerosis. Methods: We induced experimental atherosclerosis in ApoE-/-IRF1-/- mice and evaluated the effect of IRF1 on disease progression and foam cell formation. Results: IRF1 expression was increased in human and mouse atherosclerotic lesions. IRF1 deficiency inhibited modified lipoprotein uptake and promoted cholesterol efflux, along with altered expression of genes implicated in lipid metabolism. Gene expression analysis identified scavenger receptor (SR)-AI as a regulated target of IRF1, and SR-AI silencing completely abrogated the increased uptake of modified lipoprotein induced by IRF1. Our data also explain a mechanism underlying endotoxemia-complicated atherogenesis as follows: two likely pro-inflammatory agents, oxidized low-density lipoprotein (ox-LDL) and bacterial lipopolysaccharide (LPS), exert cooperative effects on foam cell formation, which is partly attributable to a shift of IRF1-Ubc9 complex to IRF1- myeloid differentiation primary response protein 88 (Myd88) complex and subsequent IRF1 nuclear translocation. Additionally, it seems that improved function of vascular smooth muscle cells (VSMCs) also accounts for the diminished and more stable atherosclerotic plaques observed in ApoE-/-IRF1-/- mice. Conclusions: Our findings demonstrate an unanticipated role of IRF1 in the regulation of gene expression implicated in foam cell formation and identify IRF1 activation as a new risk factor in the development, progression and instability of atherosclerotic lesions.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1013-1019, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418350

RESUMO

OBJECTIVE: To investigate the effect of silencing LNK gene on the expression of EPO and EPOR in acute myeloid leukemia cells (THP-1). METHODS: THP-1 cells were cultured. The lentivirus was used as a vector to silence the LNK gene stably. After 72 hours of infection, GFP expression level was detected by the fluorescent inverted microscopy. The lentiviral Infection efficiencies were monitored by flow cytometry. The LNK silencing effect was confirmed. The mRNA expressions of EPO and EPOR were detected by RT-PCR. The protein levels of LNK, EPO and EPOR were detected by Western blot. RESULTS: At the time-point of 72 hours after lentivirus infection, the expression level of GFP was above 85% detected by fluorescent inverted microscopy. The infection efficiency was above 99% by flow cytometry. mRNA expressions of LNK, EPO and EPOR in LNK silencing group were signifycantly lower than those in control group (P<0.05). The protein levels of LNK, EPO and EPOR in LNK silencing group were significantly lower than those in the control group (P<0.05). CONCLUSION: THP-1 cell line of LNK gene silencing has been successfully established,the LNK gene has been silenced, the expression of EPO and EPOR decrease, indicating that LNK may participate in the regulation of EPO and EPOR.


Assuntos
Proteínas/genética , Western Blotting , Eritropoetina , Inativação Gênica , Humanos , Receptores da Eritropoetina , Células THP-1
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1026-1032, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418352

RESUMO

OBJECTIVE: To investigate the expression of erythropoietin (EPO) and erythropoietin receptor (EPOR) in patients with acute leukemia (AL) and its clinical significance. METHODS: The levels of EPO and EPOR in plasma were determined by ELISA kit. mRNA expression levels of EPO and EPOR were determined by RT-RCR. The protein expression levels of EPO and EPOR were detected by Western blot. RESULTS: The EPO protein levels in marrow plasma of ALL and AML group were significantly higher than those in the control group (P<0.05), EPOR protein levels in ALL and AML group were significantly lower than those in the control group (P<0.05). The mRNA levels of EPO and EPOR in ALL and AML groups were significantly higher than those in the control group (P<0.05). The mRNA levels of EPO and EPOR in the high risk ALL and AML groups were significantly higher than those in the medium, low risk group and the control group (P<0.05). The protein expression levels of EPO and EPOR in ALL and AML groups were significantly higher than that in control group (P<0.05). The mRNA levels of EPO and EPOR in ALL and AML groups did not correlate with hemoglobin level and erythrocyte count (P>0.05). CONCLUSION: The expressions of EPO and EPOR is higher in ALL and AML patients. The expression levels of EPO and EPOR relate with the risk of ALL and AML. High risk patients have higher expression levels of EPO and EPOR, however, the expression levels of EPO and EPOR do not correlate with hemoglobin level and erythrocyte counting.


Assuntos
Leucemia Mieloide Aguda , Medula Óssea , Eritropoetina , Expressão Gênica , Humanos , Receptores da Eritropoetina
9.
Nat Commun ; 10(1): 3381, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358742

RESUMO

Controlling magnetism through non-magnetic means is highly desirable for future electronic devices, as such means typically have ultra-low power requirements and can provide coherent control. In recent years, great experimental progress has been made in the field of electrical manipulation of magnetism in numerous material systems. These studies generally do not consider the directionality of the applied non-magnetic potentials and/or magnetism switching. Here, we theoretically conceive and experimentally demonstrate a non-magnetic one-way spin switch device using a spin-orbit coupled Bose-Einstein condensate subjected to a moving spin-independent repulsive dipole potential. The physical foundation of this unidirectional device is based on the breakdown of Galilean invariance in the presence of spin-orbit coupling. Such a one-way spin switch opens an avenue for designing quantum devices with unique functionalities and may facilitate further experimental investigations of other one-way spintronic and atomtronic devices.

10.
Chem Commun (Camb) ; 55(63): 9299-9302, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31298666

RESUMO

Two novel POM-based huge clusters modified by conjugated organic ligands (DAPSC), {Fe10P4W32} and {Fe8MoW18}, have been successfully isolated. Compound 1 consists of a novel huge inorganic building block {Fe10P4W32} and four organic groups DAPSC linked by ten iron ions and four sodium ions. The DAPSC ligands enhance the electric delocalization effects of polyoxoanions, leading to strengthening of the third-order nonlinear optical (NLO) responses of compounds 1-2. Additionally, the oxygen evolution reaction (OER) electrocatalytic activity and the magnetic properties of compound 1 have also been investigated.

11.
Int Arch Allergy Immunol ; 180(2): 120-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256157

RESUMO

BACKGROUND: Allergen immunotherapy (AIT) is the only etiological and potentially curative therapy for allergic rhinitis (AR). OBJECTIVES: We sought to investigate the role of epigenetic regulator enhancer of zeste homolog 2 (EZH2) in the activation of dendritic cells (DCs) in AIT. METHOD: In this study, EZH2 expression in circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were evaluated using flow cytometry. Clinical information from 56 AR patients receiving AIT was collected, including 30 subjects with subcutaneous immunotherapy (SCIT) and 26 subjects with sublingual immunotherapy (SLIT). In vitro, the effect of EZH2 inhibitor, 3 Deazaneplanocin A (DZNep), on the phenotypic and functional activation of monocyte-derived DCs (moDCs) was evaluated. RESULTS: EZH2 expression in circulating mDCs and pDCs were both negatively correlated to treatment time of AIT (r = -0.39, p = 0.003 and r = -0.47, p = 0.0002, respectively). Furthermore, there was a higher correlation between EZH2 expression and AIT treatment time in the SCIT group compared to that of the SLIT group in mDCs (r = -0.42, p = 0.02 vs. r = -0.23, p = 0.26)and pDCs (r = -0.52, p = 0.003 vs. r = -0.33, p = 0.10). In vitro, the co-stimulatory molecules on moDCs, such as CD80, CD86, and CD83, were significantly inhibited by DZNep in a dose-dependent manner. The -DC-driven T-cell proliferation was suppressed by DZNep (MD = 22.88, 95% CI 7.809-37.96, p < 0.05). CONCLUSIONS: Our study shows that EZH2, which is required in the activation of DCs, mediates the epigenetic modification in AIT and stresses the importance of patient adherence during AIT.

12.
Int Immunopharmacol ; 75: 105744, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319358

RESUMO

Although the infiltration of monocytes into local lesions is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the role of metalloproteinase (MMP)/tissue inhibitor of metalloproteinases (TIMP) imbalance in the migration/invasion of THP-1 cells induced by Treponema pallidum (T. pallidum). The influence of T. pallidum on the invasion and migration of THP-1 cells was evaluated. Changes in the MMP/TIMP balance and the mechanisms underlying the involvement of the MAPK and NF-κB signaling pathways in this process were explored. T. pallidum induced the migration/invasion of THP-1 cells and the mRNA and protein expression of MMP-1, MMP-9 and TIMP-1. The mRNA expression of TIMP-2 was reduced, and the protein expression of TIMP-2 was not changed. The MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were increased. Inhibition of JNK, MEK/ERK, p38 MAPK and NF-κB significantly decreased the MMP/TIMP ratio and ultimately suppressed the migration/invasion of THP-1 cells. These findings revealed that MMP/TIMP imbalances induced by T. pallidum enhanced THP-1 cell migration and invasion via MAPK and NF-κB signaling pathway activation, which revealed a novel step in syphilis pathophysiology.

13.
Int J Biol Macromol ; 138: 912-918, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362022

RESUMO

Fruit flies (Drosophilidae: Drosophila) are commonly found in daily life and have long been used as model organisms in biology researches. Drosophila mercatorum is one important member of the Drosophila genus and has been used to study centrosome assembly of cells. In this study, we sequenced and analyzed the mitochondrial genome (mitogenome) of D. mercatorum, finding that it contains the typical structure of 37 genes and a control region. The arrangement of mitochondrial genes is in accordance with that in other Drosophila species, which is considered the ancestral organization of insects' mitogenomes. Phylogenetic analyses were performed based on 23 species of Drosophila. Our results supported two monophyletic subgenera, Drosophila and Sophophora, except for D. willistoni which was presented as an early offshoot of Drosophila. The topology ((D. yakuba + D. erecta) + D. melanogaster) was supported. We further compared the mitogenomes of parthenogenesis and sexual reproduction strains of D. mercatorum. However, only one synonymous mutation in COI gene was identified, indicating mitogenomic evolution is not strongly correlated with the different reproductive modes of this species. Taken together, our results demonstrate that mitogenome is an effective molecular marker that can be further used in phylogenetic studies of Drosophila and other organisms.

14.
Biomed Chromatogr ; 33(10): e4631, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254484

RESUMO

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cinacalcet in human plasma was developed and validated. This assay was based on liquid-liquid extraction and cinacalcet-d4 was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase A of water (containing 0.1% formic acid) and the mobile phase B of acetonitrile-water (95:5, v/v) (containing 0.2% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 358.2 → m/z 155.2 for cinacalcet and m/z 362.3 → m/z 155.0 for IS at positive ionization mode. The calibration curve was established over the range 0.05-20.0 ng/mL and the correlation coefficient was >0.99. The intra- and inter-day relative standard deviations were <5.8%. Accuracy determined at four concentrations ranged between 96.0 and 106.0%. This method was successfully applied to a pharmacokinetic description of oral dose of cinacalcet and the significant effect of food intake on the pharmacokinetics of cinacalcet was first demonstrated in Chinese healthy volunteers.

15.
BMC Complement Altern Med ; 19(1): 131, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200701

RESUMO

BACKGROUND: The effects of acupuncture on in vitro fertilization (IVF) outcomes remain controversial. And the variation in participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. METHODS: We searched digital databases for relevant studies, including Embase, PubMed, Cochrane Library and some Chinese databases up to December 2018, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF. We included studies with intervention groups using needling, and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of eight pre-specified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. RESULTS: Twenty-seven studies with 6116 participants were included. The pooled clinical pregnancy rate (CPR) from all of acupuncture groups was significantly greater than that of control groups (RR 1.21, 95% CI: 1.07-1.38), whereas the pooled live birth rate (LBR) was not. Meta-regression subgroup analysis showed a more significant benefit of acupuncture for repeated IVF cycle proportion (number of women with a history of prior unsuccessful IVF attempt divided by number of women included in each trial) ≥ 50% group (CPR: RR 1.60, 95% CI: 1.28-2.00; LBR: RR 1.42, 95% CI: 1.05-1.92), and this covariate explained most of the heterogeneity (CPR and LBR: adjusted R2 = 100 and 87.90%). Similar results were found between CPR and number of acupuncture treatments (CPR: p = 0.002, adjusted R2 = 51.90%), but not LBR. CONCLUSIONS: Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.


Assuntos
Terapia por Acupuntura , Fertilização In Vitro , Feminino , Humanos , Gravidez , Resultado da Gravidez
16.
J Diabetes Investig ; 2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31102492

RESUMO

AIMS/INTRODUCTION: Metformin, a widely prescribed antidiabetic agent, has been shown to exhibit anti-inflammatory effects in obese and type 2 diabetes patients, but the mechanism is not well elucidated. Microribonucleic acids (miRNAs) are a group of small non-coding ribonucleic acids that participate in many biological and pathological processes. The aim of the present study was to investigate whether Dicer, a key miRNA biogenesis enzyme, and miRNAs in macrophages are implicated in the anti-inflammatory effects of metformin. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were carried out to verify the anti-inflammatory effects of metformin. miRNA microarray was applied to detect the expression profile of miRNA. Western-blotting, enzyme-linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were used to examine the role Dicer and miRNAs play in the anti-inflammatory effects of metformin. RESULTS: In parallel with the suppression of interleukin-6 and tumor necrosis factor-α production in resting and lipopolysaccharide-stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs. When Dicer was knocked down, the anti-inflammatory effects of metformin were significantly attenuated. Additionally, the upregulation of miRNA (miR)-34a-5p and miR-125b-5p by metformin were also blunted in Dicer knockdown macrophages. Furthermore, inhibition of miR-34a-5p and miR-125b-5p could impair the suppressive action of metformin on pro-inflammatory factors production, whereas overexpression of the two miRNAs mimicked the anti-inflammatory effects of metformin. CONCLUSIONS: Metformin might show anti-inflammatory effects in macrophages through the induction of Dicer and the subsequent upregulation of miR-34a-5p and miR-125b-5p.

17.
Prev Sci ; 20(6): 904-913, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31073817

RESUMO

"Just-in-time" interventions (JITs) delivered via smartphones have considerable potential for reducing HIV risk behavior by providing pivotal support at key times prior to sex. However, these programs depend on a thorough understanding of when risk behavior is likely to occur to inform the timing of JITs. It is also critical to understand the most important momentary risk factors that may precede HIV risk behavior, so that interventions can be designed to address them. Applying machine learning (ML) methods to ecological momentary assessment data on HIV risk behaviors can help answer both questions. Eighty HIV-negative men who have sex with men (MSM) who were not on PrEP completed a daily diary survey each morning and an experience sampling survey up to six times per day via a smartphone application for 30 days. Random forest models achieved the highest area under the curve (AUC) values for classifying high-risk condomless anal sex (CAS). These models achieved 80% specificity at a sensitivity value of 74%. Unsurprisingly, the most important contextual risk factors that aided in classification were participants' plans and intentions for sex, sexual arousal, and positive affective states. Findings suggest that survey data collected throughout the day can be used to correctly classify about three of every four high-risk CAS events, while incorrectly classifying one of every five non-CAS days as involving high-risk CAS. A unique set of risk factors also often emerge prior to high-risk CAS events that may be useful targets for JITs.

18.
Zhen Ci Yan Jiu ; 44(3): 211-5, 2019 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-30945505

RESUMO

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of patients with knee osteoarthritis (KOA) in the early stage. METHODS: A total of 60 KOA patients were randomized into medication group and acupuncture combined with medication (acupuncture) group (n= 30 in each group). Patients of the medication group were treated by external application of Diclofenac Diethylamine Emulgel around the affected joint, 3 times a day for 2 successive weeks and reasonable exercising training. Patients of the acupuncture group received routine medication and reasonable exercising training and acupuncture of Ashi-points, Zusanli (ST36), Yanglingquan (GB34), Yinlingquan (SP9), Neixiyan (EX-LE4) and Dubi (ST35) at affected side with filiform needles which were manipulated with uniform reinforcing-reducing method for a while, followed by retaining the needles for 30 min. The treatment was conducted once every other day for 2 weeks. The pain degree was assessed by using visual analog scale (VAS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scale (0-240 points) was used to evaluate the severity of KOA, and the "Diagnosis of Syndromes of Traditional Chinese Medicine" was used to assess the therapeutic effect after the treatment. RESULTS: After the treatment, the VAS and WOMAC scores of both medication and acupuncture groups were significantly and respectively decreased in comparison with their own pre-treatment (P<0.05), and the scores of the two indexes of the acupuncture group were evidently lower than those of the medication group (P<0.05). Of the two 30 cases in the medication and acupuncture groups, 5 (16.67%) and 6 (20.00%) were cured, 17 (56.67%) and 19 (63.33%) experienced marked improvement, 6 (20.00%) and 4 (13.33%) were effective, 2 (6.67%) and 1 (3.33%) were ineffective, with the effective rate of cure plus marked effectiveness being 73.33% and 83.33%, respectively. No significant difference was found between the two groups in the therapeutic effect (P>0.05). CONCLUSION: Acupuncture combined with medication has a better therapeutic effect in the treatment of KOA in the early stage than that of the simple medication.


Assuntos
Terapia por Acupuntura , Osteoartrite do Joelho , Humanos , Medicina Tradicional Chinesa , Osteoartrite do Joelho/terapia , Medição da Dor , Resultado do Tratamento
19.
Genomics Proteomics Bioinformatics ; 17(1): 52-63, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31028880

RESUMO

Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.


Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
20.
Biometrics ; 75(3): 788-798, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31009067

RESUMO

This paper presents Granger mediation analysis, a new framework for causal mediation analysis of multiple time series. This framework is motivated by a functional magnetic resonance imaging (fMRI) experiment where we are interested in estimating the mediation effects between a randomized stimulus time series and brain activity time series from two brain regions. The independent observation assumption is thus unrealistic for this type of time-series data. To address this challenge, our framework integrates two types of models: causal mediation analysis across the mediation variables, and vector autoregressive (VAR) models across the temporal observations. We use "Granger" to refer to VAR correlations modeled in this paper. We further extend this framework to handle multilevel data, in order to model individual variability and correlated errors between the mediator and the outcome variables. Using Rubin's potential outcome framework, we show that the causal mediation effects are identifiable under our time-series model. We further develop computationally efficient algorithms to maximize our likelihood-based estimation criteria. Simulation studies show that our method reduces the estimation bias and improves statistical power, compared with existing approaches. On a real fMRI data set, our approach quantifies the causal effects through a brain pathway, while capturing the dynamic dependence between two brain regions.

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