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1.
Carbohydr Polym ; 227: 115323, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590841

RESUMO

Bacterial nanocellulose (BNC) has many advantages over plant cellulose, which make it widely used in many fields, especially in the food industry. In this study, three strains including BCA263, BCC529, and P1 were selected for characteristics analysis of BNCs under static and agitated culture conditions. The BNCs produced under static culture condition were in the shape of uniform membrane, while BNCs produced under agitated culture were in form of small agglomerates and fragments. BCA263 and BCC529 strains were more suitable for static culture, while P1 strain was more suitable for agitated culture. BNCs produced under static culture condition exhibited higher crystallinity, stronger tensile strength, denser network structure, higher temperature resistance and good flame retardancy; while BNCs produced under agitated culture condition exhibited larger porous and lower crystallinity. Furthermore, BNCs produced under agitated culture condition were more suitable as a stabilizer of coffee milk beverage.

2.
Am J Hum Genet ; 105(4): 763-772, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564439

RESUMO

Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

3.
Small ; : e1904314, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31565866

RESUMO

Human mesenchymal stem cells (hMSCs), due to their immune regulation and collateral secretion effects, are currently explored for potential therapy of idiopathic pulmonary fibrosis (IPF). Understanding the migration, homing, functions, and survival of transplanted hMSCs in vivo is critical to successful IPF treatment. Therefore, it is highly desired to develop noninvasive and effective imaging technologies to track the transplanted hMSCs, providing experimental basis for improving the efficacy of hMSCs in the treatment of IPF. The rational design and development of a dual-labeling strategy are reported by integrating gold nanoparticle (AuNP)-based computed tomography (CT) nanotracers and red-emitting firefly luciferase (RfLuc)-based bioluminescence (BL) tags for CT/BL multimodal imaging tracking of the transplanted hMSCs in a murine model of IPF. In this approach, the CT nanotracer is prepared by sequential coupling of AuNPs with polyethylene glycol and trans-activator of transcription (TAT) peptide (Au@TAT), and employed it to monitor the location and distribution of the transplanted hMSCs in vivo by CT imaging, while RfLuc is used to monitor hMSCs viability by BLI. This facile strategy allows for visualization of the transplanted hMSCs in vivo, thereby enabling profound understanding of the role of hMSCs in the IPF treatment, and advancing stem cell-based regenerative medicine.

4.
Org Lett ; 21(18): 7342-7345, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31478381

RESUMO

An efficient and convenient cobalt-catalyzed ortho-C(sp2)-H amidation of benzaldehydes employing dioxazolones as the aminating reagent has been developed. The key feature of this protocol is the use of green and economic earth-abundant metals cobalt as the catalyst with the p-chloroaniline as the transient directing group. Further application of our approach was demonstrated by the synthesis of C1r serine protease inhibitor 45 and elastase inhibitor 49.

5.
Sleep Breath ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473914

RESUMO

PURPOSE: Obstructive sleep apnea syndrome (OSAS) was suggested to exert an effect on renal function. However, the specific mechanism was still unknown. We try to find the association among OSAS, adiponectin, and cystatin C and the effect of adiponectin on renal function in OSAS patients. METHODS: Seventeen healthy men and seventy-three men which only had OSAS were included in the end. Apnea-hypopnea index (AHI), oxygen desaturation index (ODI), the percentage of total sleep time spent with SpO2 < 90% (T90%), lowest O2 saturation (LaSO2), Epworth Sleepiness Scale (ESS) score, serum adiponectin, and high-sensitive C-reactive protein (hsCRP) were detected in all subjects, and renal function was evaluated with creatinine, cystatin C, and estimated glomerular filtration rate (eGFR). RESULTS: Demographic data, creatinine, and eGFR did not differ among the studied groups. Decreased serum adiponectin levels were associated with severe OSAS. OSAS patients had a higher hsCRP and cystatin C than those without OSAS. Serum adiponectin levels had a negative association with cystatin C. After adjusted for confounders, adiponectin, hsCRP, and ODI had a significant prediction on the cystatin C (ß = - 0.218, p = 0.011; ß = 0.226, p = 0.037; and ß = 0.231, p = 0.029). CONCLUSIONS: Decreased serum adiponectin was associated with increased cystatin C in male OSAS patients. These results suggest that serum adiponectin might be a regulatory factor for renal function in OSAS.

6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 583-588, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537241

RESUMO

Objective To explore the effect of prostaglandin E2 (PGE2) on the phenotype and chemotaxis of mouse bone marrow-derived dendritic cells (BMDCs). Methods BMDCs isolated from murine bone marrow and cultured in vitro were divided into 6 groups (0 µg/mL PGE2 group, 1 µg/mL PGE2 group, 5 µg/mL PGE2 group, 0 µg/mL PGE2 plus LPS group, 1 µg/mL PGE2 plus LPS group, 5 µg/mL PGE2 plus LPS group). The expression of surface makers CD40, CD86, major histocompatibility complex II (MHCII), CC chemokine receptor 7 (CCR7) were detected by flow cytometry. The expression of CCR7 protein was detected by Western blot analysis. The migration ability of BMDCs was detected by TranswellTM assay. The survival rate of BMDCs was detected by CCK-8 assay. Results PGE2 of 1 µg/mL increased the expression of surface molecules on BMDCs and promoted the migration ability of BMDCs. PGE2 of 5 µg/mL reduced the expression of surface molecules on BMDCs and inhibited the migration ability of BMDCs. The change of PGE2 concentration did not affect the survival rate of BMDCs. Conclusion PGE2 was demonstrated a dual regulatory effect on the migration of BMDCs. Low concentration of PGE2 can promote the migration ability of BMDCs, while high concentration of PGE2 shows contrary effect.


Assuntos
Medula Óssea , Movimento Celular , Células Dendríticas/citologia , Dinoprostona/farmacologia , Animais , Antígeno B7-2/metabolismo , Antígenos CD40/metabolismo , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR7/metabolismo
7.
Plant Physiol Biochem ; 144: 118-126, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31563092

RESUMO

As nitrogen deposition increases, acid rain is gradually shifting from sulfuric acid rain (SAR) to nitric acid rain (NAR). Acid rain can severely affect plant growth, damage ecosystems, and reduce biodiversity. Thus, a shift in acid rain type presents another challenge to the conservation of endangered plant species. We investigated the effect of three acid rain types (SAR, mixed acid rain [MAR], and NAR) and pH on the growth of an endangered Chinese endemic tree, Horsfieldia hainanensis Merr., using simulated rain in a greenhouse environment. Over nine months, growth indices, chlorophyll content, antioxidant enzyme activity, malondialdehyde content, and chlorophyll fluorescence parameters were investigated for treated and control saplings. The results indicated that at a pH of 5.6, H. hainanensis could adapt to SAR and MAR, but NAR inhibited below-ground growth. At a pH of 2.5 and 4.0, SAR inhibited stem and leaf biomass accumulation, whereas NAR inhibited root biomass accumulation and altered root morphology. MAR had intermediary effects between those of SAR and NAR. Adverse effects on leaf physiology were reduced as the rain type shifted from SAR to NAR; however, roots were increasingly adversely affected. Our results suggest that conservation efforts for H. hainanensis should shift from an above-ground to a below-ground focus as acid rain transitions toward NAR.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31486262

RESUMO

Supramolecular ensembles adopting ring-in-ring structures are less developed compared with catenanes featuring interlocked rings. While catenanes with inter-ring closed-shell metallophilic interactions, such as d10 -d10 AuI -AuI interactions, have been well-documented, the ring-in-ring complexes featuring such metallophilic interactions remain underdeveloped. Herein is described an unprecedented ring-in-ring structure of a AuI -thiolate Au12 cluster formed by recrystallization of a AuI -thiolate Au10 [2]catenane from alkane solvents such as hexane, with use of a bulky dibutylfluorene-2-thiolate ligand. The ring-in-ring AuI -thiolate Au12 cluster features inter-ring AuI -AuI interactions and underwent cluster core change to form the thermodynamically more stable Au10 [2]catenane structure upon dissolving in, or recrystallization from, other solvents such as CH2 Cl2 , CHCl3 , and CH2 Cl2 /MeCN. The cluster-to-cluster transformation process was monitored by 1 H NMR and ESI-MS measurements. Density functional theory (DFT) calculations were performed to provide insight into the mechanism of the "ring-in-ring⇌ [2]catenane" interconversions.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 998-1003, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537227

RESUMO

OBJECTIVE: To investigate the value of renal resistive index (RRI) in early predictor and discriminator of severe acute pancreatitis (SAP)-related acute kidney injury (AKI). METHODS: A retrospective observational study was conducted. SAP patients complicated with AKI (within 1 week of onset) and admitted to intensive care unit (ICU) of Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2016 to June 2019 were enrolled. The RRI within 24 hours admission was measured. Clinical data such as acute physiology and chronic health evaluation II (APACHE II), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), intra-abdominal pressure (IAP), arterial blood lactate (Lac), oxygenation index (PaO2/FiO2), base excess (BE), serum creatinine (SCr), urine output, norepinephrine (NE) and RRI were collected. Within 24 hours and 7 days after ICU admission, patients were grouped according to AKI classification criteria of Kidney Disease: Improving Global Outcomes (KDIGO), and the differences of relevant parameters were statistically analyzed. Influence factors of AKI grading were screened by Logistic regression analysis. Pearson correlation analysis was used to analyze the correlation between RRI and other parameters. The predictive value of RRI for AKI classification was analyzed by receiver operating characteristic (ROC) curve. RESULTS: A total 57 patients were included, with an average age of (54.6±13.5) years old, and APACHE II score of 21.8±5.6. Within 24 hours, the number of patients suffered from stage 1-3 AKI were 19 (33.3%), 18 (31.6%) and 20 (35.1%), respectively. On day 7, the number of patients suffered from stage 0-3 AKI were 21 (36.9%), 8 (14.0%), 9 (15.8%) and 19 (33.3%), respectively. The higher APACHE II score, CVP, IAP, Lac, NE dosage and RRI were found in the group with higher AKI grades, especially in the group with stage 3 AKI on day 7. RRI of patients with stage 3 AKI was significantly higher than that of patients with stage 1 and 2 AKI within 24 hours (0.74±0.04 vs. 0.65±0.05, 0.68±0.05, both P < 0.05). Similarly, RRI of patients with stage 2 and 3 AKI were significantly higher than that of patients with stage 0 and 1 AKI on day 7 (0.70±0.04, 0.74±0.04 vs. 0.65±0.05, 0.66±0.05, all P < 0.05). Multivariate Logistic regression analysis showed that RRI was an independent factor of AKI classification [odds ratio (OR) = 3.15, 95% confidence interval (95%CI) = 1.09-9.04, P < 0.05], and IAP and CVP also had significant impacts on AKI grading [OR value was 2.11 (95%CI = 1.16-4.22), 3.78 (95%CI = 1.21-12.90), both P < 0.05]. ROC curve analysis showed that the area under curve (AUC) of RRI for predicting AKI ≥2 stage was 0.87 (P < 0.05); the cut-off > 0.71, sensitivity was 71% and specificity was 83%. The correlation analysis showed that RRI was positively correlated to a certain extent with IAP and lactic acid (r1 = 0.49, r2 = 0.39, both P < 0.05). CONCLUSIONS: High RRI on ICU admission was a significant predictor for development of severe AKI during the first week, and RRI can help predict the tendency of AKI in SAP.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31535693

RESUMO

OBJECTIVES: To develop classification algorithms that accurately identify axial SpA (axSpA) patients in electronic health records, and compare the performance of algorithms incorporating free-text data against approaches using only International Classification of Diseases (ICD) codes. METHODS: An enriched cohort of 7853 eligible patients was created from electronic health records of two large hospitals using automated searches (⩾1 ICD codes combined with simple text searches). Key disease concepts from free-text data were extracted using NLP and combined with ICD codes to develop algorithms. We created both supervised regression-based algorithms-on a training set of 127 axSpA cases and 423 non-cases-and unsupervised algorithms to identify patients with high probability of having axSpA from the enriched cohort. Their performance was compared against classifications using ICD codes only. RESULTS: NLP extracted four disease concepts of high predictive value: ankylosing spondylitis, sacroiliitis, HLA-B27 and spondylitis. The unsupervised algorithm, incorporating both the NLP concept and ICD code for AS, identified the greatest number of patients. By setting the probability threshold to attain 80% positive predictive value, it identified 1509 axSpA patients (mean age 53 years, 71% male). Sensitivity was 0.78, specificity 0.94 and area under the curve 0.93. The two supervised algorithms performed similarly but identified fewer patients. All three outperformed traditional approaches using ICD codes alone (area under the curve 0.80-0.87). CONCLUSION: Algorithms incorporating free-text data can accurately identify axSpA patients in electronic health records. Large cohorts identified using these novel methods offer exciting opportunities for future clinical research.

11.
Pharmacol Res ; : 104445, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31526872

RESUMO

Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. A significant increase in ganglioside GM3 content generally happens in atherosclerotic plaques causing a GM3-enriched microenvironment. It remains unclear whether the GM3-enriched microenvironment influences atherogenesis. This study sought to answer the question by investigating exogenous GM3 effects on multiple steps involved in atherogenesis. First, the physicochemical properties of native low-density lipoprotein (LDL) and LDL enriched with exogenous GM3 (GM3-LDL) were characterized by dynamic laser scattering, atomic force microscopy, and agarose gel electrophoresis. Then, electrophoretic mobility, conjugated diene and malondialdehyde production, and amino group blockage of GM3-LDL/LDL were measured to determine LDL oxidation degrees and cellular recognition/internalization of GM3-LDL/GM3-oxLDL were detected via confocal microscopy and flow cytometry. Subsequently, influences of exogenous GM3 addition on the monocyte-adhering ability of endothelial cells and on lipid deposition in macrophages were investigated. Finally, exogenous GM3 effect on atherogenesis was evaluated using apoE-/- mice fed a high-fat diet. We found that exogenous GM3 addition increased the size, charge, and stability of LDL particles, reduced LDL susceptibility to oxidation and its cellular recognition/internalization, impaired the monocyte-adhering ability of endothelial cells and lipid deposition in macrophages. Moreover, exogenous GM3 treatment also significantly decreased blood lipid levels and atherosclerotic lesion areas in atherosclerotic mice. The data imply that exogenous GM3 had an inhibitory effect on atherogenesis, suggesting a protective role of a GM3-enriched microenvironment in atherosclerotic plaques and implying a possibility of exogenous GM3 as an anti-atherosclerotic drug.

12.
Biomaterials ; 221: 119419, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421315

RESUMO

An unpredicted side effect of photothermal therapy (PTT) is agitated by hyperthermia which results in damage to healthy tissue. Developing PTT platforms, enabling effective tumor ablation under mild irradiation conditions, is of wide interest, but challenging. Here, we investigated bismuth crystals embedded silica (Bi@SiO2) nanoparticles, loaded with an autophagy inhibitor (chloroquine, CQ). It was found that SiO2 effectively prevented the oxidization of Bi nanocrystals in the physiological environment and could serve as a scatter layer to improve NIR absorption, enabling a high photothermal conversion efficiency (~43%) and excellent photostability. Furthermore, the findings indicated that CQ molecules, delivered intracellularly by the particles, significantly weakened the degradation of autolysosomes by lysosome within the tumor cells, thus inducing suppression effect to autophagy and resistance to photothermia. Both in vitro and in vivo anti-tumor effects were consequently promoted owing to the combined effects enabled by Bi@SiO2-CQ nanoparticles under mild NIR irradiation conditions. This study demonstrates a potential new PTT platform with superior therapeutic efficacy.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31428896

RESUMO

Liver dysfunction is associated with adverse events in infective endocarditis (IE). However, few studies have explored the predictive value of conjugated bilirubin (CB) in IE. We aimed to investigate the nature of the link between CB and adverse prognosis in patients with IE. Consecutive patients with IE between January 2009 and July 2015 were enrolled. Multivariate analysis was performed to confirm whether CB was an independent risk factor for adverse outcomes. In all, 1010 patients were included and divided into two groups according to admission CB level (µmol/L): normal (≤ 7.0, n = 820) and elevated (> 7.0, n = 190) CB groups. In-hospital mortality (5.0% vs. 22.1%, p < 0.001) and major adverse cardiac events (16.8% vs. 36.3%, p < 0.001) were significantly higher in patients with increased CB. A possible J-shaped relationship was found between CB and in-hospital events. Further, CB had more predictive power than total bilirubin in predicting in-hospital death (AUC 0.715 vs. 0.674, p = 0.010). Elevated CB was an independent predictor of in-hospital death (adjusted OR = 2.62, 95%CI 1.40-4.91, p = 0.003). Moreover, CB (increment 1 µmol/L) was independently associated with higher long-term mortality. Kaplan-Meier curves indicated that patients with elevated CB were associated with higher cumulative rate of long-term death (log-rank = 21.47, p < 0.001). CB, a biomarker of liver function, was a relatively powerful predictor of in-hospital and long-term adverse prognosis of IE and could likely comprise a novel risk evaluation strategy.

14.
J Microbiol ; 57(9): 759-768, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376108

RESUMO

The cultivation of microbial species remains a primary challenge in microbiology and obtaining pure cultures is essential for the study of microbial physiology and function. When isolating microorganisms from aquaculture environments, Vibrio are the most dominate isolates on the media that are commonly used. In order to expand our ability to study microbial species, an easy-operation and low-cost medium that can reduce the interference of Vibrio strains and increase the cultivability of other bacteria is urgently needed. We compared viable cell counts on conventional media (CM; including Marine Agar 2216 and LB media) and diluted media (DM; including 1/10-Marine Agar 2216, 1/10-LB). We also assessed the diversity of cultivable microorganisms under high and low nutrient conditions by a plate-wash strategy coupled with high-throughput sequencing of the V4 hypervariable region of the 16S rRNA gene. The results show that microbial communities from DM, especially 1/10-Marine Agar 2216, are more diverse than those obtained from CM. Vibrio isolates were reduced on DM. PICRUSt analysis revealed that nutrient composition is a significant contributor to the diversity and function of the cultivable microbial communities. Bacteria grown on CM possess more pathogenic characteristics, whereas DM favors the growth of bacteria that have multiple metabolic functions. Collectively, our data provide strong evidence that dilution of CM influences the cultivability of bacteria from aquaculture seawater. It also supports that DM can expand the range of microbial species that can be cultivated. This study also provides insights for media design in microbial cultivation from aquaculture systems.


Assuntos
Meios de Cultura/metabolismo , Água do Mar/microbiologia , Vibrio/crescimento & desenvolvimento , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Meios de Cultura/química , DNA Bacteriano/genética , Filogenia , RNA Ribossômico 16S/genética , Vibrio/genética , Vibrio/isolamento & purificação , Vibrio/metabolismo
15.
J Invertebr Pathol ; 166: 107231, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425685

RESUMO

Virus-like particles (VLPs) are potential containers for delivery of therapeutic agents at the nanoscale. In this study, the capsid protein of Infectious hypodermal and hematopoietic necrosis virus (IHHNV) was expressed in a baculovirus insect cell system. The 37-kDa recombinant protein containing the hexahistidine residues (His Tag) at N-terminal was purified using immobilized metal affinity chromatography (IMAC) and assembled into VLPs with a diameter of 23 ±â€¯3 nm analyzed by transmission electron microscopy. We also verified that disassembly/reassembly of IHHNV-VLPs was controlled in the presence and absence of DTT. The efficiency of IHHNV-VLPs to encapsulate plasmid DNA was about 48.2%, and the VLPs encapsulating the pcDNA3.1(+)-EGFP plasmid DNA could recognize the primary shrimp hemocytes and deliver the loaded plasmid into cells by detection of expressed enhanced green fluorescent protein (EGFP). These results implied that the IHHNV-VLPs might be a good candidate for packaging and delivery of expressible plasmid DNA, and may produce an antiviral product in shrimp cells for gene therapy.

16.
Org Biomol Chem ; 17(34): 7854-7857, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31408075

RESUMO

A copper-catalyzed DTBP oxidative dual C-H sulfurization has been developed for the direct thiocarbamation of imidazopyridines using a combination of elemental sulfur and formamides as carbamothioyl surrogates. NBS (bromo succinimide) was found to promote the thiocarbamation in good yields. This dual C-H sulfurization strategy enables access to a wide range of carbamothioyl imidazoheterocycles without the use of highly toxic phosgene.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31392828

RESUMO

BACKGROUND: Postsurgical evaluation of sinus floor elevation regularly involves linear measurements of the elevated volumes in the cone beam computed tomography (CBCT) images. The accuracy of measurements could be compromised due to ill-defined sinus floor outline if implants are placed simultaneously. PURPOSE: The aim was to examine a CBCT superimposition method to improve the measurement accuracy. MATERIALS AND METHODS: Twenty patients who received transalveolar sinus floor elevation with immediate implantation were enrolled. CBCTs before and after surgery were transformed into digital imaging and communications in medicine format and imported into the Dolphin Imaging software. Voxel-based superimposition was automated to merge the files. In the superimposed image, parameters including alveolar bone height, protruded implant length, and total elevated height were measured. The superimposition and measurements were performed independently by two examiners and in two timepoints with 1-week time interval. We used intraclass correlation coefficient (ICC) to analyze the interexaminer and intraexaminer agreements. RESULTS: Of measured parameters, the mean of difference between two timepoints ranged from 0.18 to 0.26 mm by examiner 1, and from 0.16 to 0.20 mm by examiner 2. ICCs were equal or greater than 0.98, indicating perfect intraexaminer agreement. For interexaminer reliability, the largest mean of difference was 0.27 mm in measuring alveolar bone height between two examiners. ICCs were greater than 0.98, showing perfect interexaminer agreement. CONCLUSIONS: The voxel-based superimposition of pre- and post-surgical CBCT images with Dolphin Imaging is an effective and reliable way for linear measurements so as to assess the surgical outcome. There is minimal effect on reproducibility of measured data by different timepoints or performers.

18.
Br J Clin Pharmacol ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396983

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. PEX168 pharmacokinetics (PK) was studied to identify requirements for dose-modification in T2DM complicated by renal impairment. METHODS: This was a single-center, open-labeled, parallel-group, single-dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age-, sex-, and body mass index (BMI)-matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 µg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648, and 720 h. RESULTS: Twenty-three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t1/2 (163 h) in the moderate impairment group was prolonged compared to the mild impairment (117 h) and normal (121 h) groups. AUC0-inf increased by 13% and 100.7% in patients with mild and moderate renal impairment. Most adverse events were mild gastrointestinal disorders, with only one serious adverse event observed. CONCLUSION: A single dose of 200 µg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required (ClinicalTrials.org #NCT02467790).

19.
Methods ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442560

RESUMO

Chromosome Conformation Capture (3C)-based technologies, such as Hi-C, have represented a significant breakthrough in investigating the structure and function of higher-order genome architecture. However, the mapping of global chromatin interactions remains challenging across many biological conditions due to high background noise and financial constraints, especially for small laboratories. Here, we describe the Bridge linker-Alul-Tn5 Hi-C (BAT Hi-C) method, which is a simple and efficient method for delineating chromatin conformational features of mouse embryonic stem (mES) cells and uncover DNA loops. This protocol combines Alul fragmentation and biotinylated linker-mediated proximity ligation to obtain kilobase (kb) resolution with a marked increase in the amount of unique read pairs. The protocol also includes chromatin isolation to reduce background noise and Tn5 tagmentation to cut down on preparation time. Importantly, with only one-third sequencing depth, our method revealed the same spectrum of chromatin contacts as in situ Hi-C. BAT Hi-C is an economical (i.e., approximately $40 for library preparation) and straightforward (total hands-on time of 3 days) tool that is ideal for the in-depth analysis of long-range chromatin looping events in a genome-wide fashion.

20.
Med Care ; 57(10): 809-814, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415340

RESUMO

BACKGROUND: Personal health records offer patients access to view their own health information and to manage their care online through secure patient portal tools. Little is known about the patient-reported experience in using health portals to manage chronic conditions. OBJECTIVE: In a patient-centered research study, we examined how using portal tools affects patient health care experiences among patients with chronic conditions. We also examined barriers among nonportal users. RESEARCH DESIGN: A cross-sectional patient survey. SUBJECTS: Patients with a chronic condition in an integrated delivery system offering a patient portal. MEASURES: Respondents reported barriers, preferences, and experiences in using the patient portal, and whether using the portal changed their overall health. RESULTS: Among all the 1824 respondents (70% response rate), portal nonusers reported preferring in-person health care (54%) or experiencing internet access barriers (41%). Portal users reported that using the portal was convenient (90%), the information available was useful (92%), and that it integrated well with other health care (92%). Among users, 31% reported that using the portal had improved their overall health. After adjustment, patients were significantly more likely to report that portal use improved their health if they had also reported convenience, information usefulness, or integration with other care (P<0.05). Reassuringly, patient-reported impacts on overall health did not vary by patient characteristics (including age, race, sex, education, income, complex conditions). CONCLUSION: Patients with chronic conditions using the portal reported convenience, information usefulness, and integration of the patient portal with their health care; these may act as potential pathways improving health.

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