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1.
J Affect Disord ; 298(Pt A): 43-50, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34715198

RESUMO

BACKGROUND: Distinguishing bipolar depressive disorder (BDD) from major depressive disorder (MDD) solely relying on clinical clues is a challenge. Evidence in neuroimaging have revealed potential neurological markers for the differential diagnosis. METHODS: We aimed to characterize common and specific alterations in the dynamic local functional connectivity pattern in BDD and MDD by using the dynamic regional phase synchrony (DRePS), a newly developed method for assessing intrinsic dynamic local functional connectivity. A total of 98 patients with MDD and 56 patients with BDD patients, and 97 age-, gender-, and education-matched healthy controls (HC) were included and underwent the resting-state functional magnetic resonance imaging. RESULTS: Compared with HC, patients with two disorders shared decreased DRePS value in the bilateral orbitofrontal cortex (OFC) extends to insula, the right insula extends to hippocampus, the left hippocampus, the right inferior frontal gyrus (IFG), the left thalamus extends to caudate, the right caudate, the bilateral superior frontal gyrus (SFG), and the right medial frontal gyrus (MFG). Furthermore, patients with MDD exhibited specific decreased DRePS value in the left caudate. Moreover, voxel signals in these regions during the support vector machine analysis contributed to the classification of the two diagnoses. CONCLUSIONS: Our findings provided new insight into the neural mechanism of patients with MDD and BDD and could potentially inform the diagnosis and the treatment of this disease.

2.
JAMA Netw Open ; 4(8): e2121106, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34398202

RESUMO

Importance: The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. Objective: To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China. Design, Setting. and Participants: This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate. Main Outcomes and Measures: Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography. Results: A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture. Conclusions and Relevance: In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.

3.
Eur Heart J ; 42(33): 3175-3186, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34347859

RESUMO

AIMS: Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose-response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21-1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels. CONCLUSIONS: In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306616.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , LDL-Colesterol , Fibrinolíticos/efeitos adversos , Hospitais , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do Tratamento
4.
Sci Total Environ ; 799: 149403, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364287

RESUMO

Interaction between flow and cylindrical-shaped structures generates coherent and periodic turbulent flow that is frequently experienced by fish in natural environments, influencing fish maneuvering and swimming stability. The current study evaluated the behavioral responses of hybrid sturgeon (Acipenser dabryanus ♀ × Acipenser baerii ♂) when interacting with the wake flows induced by a D-shaped cylinder, with diameter ranging from 2 to 6 cm. A two dimensional Particle Image Velocimetry (PIV) was used to measure the wake flows hydrodynamics induced by D-shaped cylinders, and the fish behavior was recorded by camera. Hydrodynamic space occupancy together with swimming behaviors were analyzed, and the result shows that due to the presence of lowest velocity and relatively low turbulence, the regions behind cylinder were characterized by the preferred station holding zone for fish. Sturgeon adopted distinctive swimming gaits (Kármán gaiting or spill) in response to the cylinder wake flow and the associated fish swimming kinematics differed from each other. Kármán gaiting and spill significantly depended on velocity, vorticity and Reynolds shear stress, and varied according to the ratio of turbulence length scale to standard fish length (Lu/Lfish), which highlights the importance of cylinder vortex structure in influencing fish holding station and swimming stability. It is envisioned that these results can provide insights into the positions where fish may prefer to occupy in natural habitats and recommendations for the design and optimization of fish-friendly projects.


Assuntos
Comportamento Animal , Oncorhynchus mykiss , Animais , Fenômenos Biomecânicos , Quimera , Feminino , Hidrodinâmica , Masculino , Oncorhynchus mykiss/fisiologia , Natação
5.
Artigo em Inglês | MEDLINE | ID: mdl-34322818

RESUMO

Nitrogen (N) is an essential nutrient limiting life, and its biochemical cycling and distribution in rivers have been markedly affected by river engineering construction and operation. Here, we comprehensively analyzed the spatiotemporal variations and driving environmental factors of N distributions based on the long-term observations (from 2004 to 2016) of seven stations in the Three Gorges Reservoir (TGR). In the study period, several water quality indexes of the river reach improved, whereas N pollution was severe and tended to be aggravated after the TGR impoundment. The anti-seasonal reservoir operation strongly affected the variations in N forms. The total nitrogen (TN) concentration in the mainstream of the Yangtze River continuously increased, although it was still lower than that in the incoming tributaries (Wu and Jialing rivers). Further analysis showed that this increase occurred probably because of external inputs, including the upstream (76%), non-point (22%), and point source pollution inputs (2%). Additionally, different N forms showed significant seasonal variations; among them, the TN and nitrate nitrogen concentrations were the lowest in the impoundment season (October-February), and the ammonia nitrogen concentrations were the highest in the sluicing season (March-May). Redundancy analysis revealed that the water level and distance to the Three Gorges Dam were significant contributors to N forms distribution. Our findings could provide a basis for managing and predicting the water quality in the Yangtze River.

6.
Environ Sci Pollut Res Int ; 28(43): 61636-61646, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34184223

RESUMO

The settlement of non-spherical particles, such as propagules of plants and natural sediments, is commonly observed in riverine ecosystems. The settling process is influenced by both particle properties (size, density, and shape) and fluid properties (density and viscosity). Therefore, the drag law of non-spherical particles is a function of both particle Reynolds number and particle shape. Herein, a total of 828 settling data are collected from the literatures, which cover a wide range of particle Reynolds number (0.008-10000). To characterize the influence of particle shapes, sphericity is adopted as the general shape factor, which varies from 0.421 to 1.0. By comparing the measured drag with the standard drag curve of spheres, we modify the spherical drag law with three shape-dependent functions to develop a new drag law for non-spherical particles. Combined with an iterative procedure, a new model is thus obtained to predict the settling velocity of non-spherical particles of various shapes and materials. Further applications in hydrochorous propagule dispersal and sediment transport are projected based on deeper understanding of the settling process.


Assuntos
Ecossistema , Tamanho da Partícula
7.
J Pharm Sci ; 110(11): 3594-3604, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34181992

RESUMO

Many monoclonal antibody (mAb) solutions exhibit high viscosity at elevated concentrations, which prevents manufacturing and injecting of concentrated mAb drug products at the small volumes needed for subcutaneous (SC) administration. Addition of excipients that interrupt intermolecular interactions is a common approach to reduce viscosity of high concentration mAb formulations. However, in some cases widely used excipients can fail to lower viscosity. Here, using infliximab and ipilimumab as model proteins, we show that caffeine effectively lowers the viscosity of both mAb formulations, whereas other common viscosity-reducing excipients, sodium chloride and arginine, do not. Furthermore, stability studies under accelerated conditions show that caffeine has no impact on stability of lyophilized infliximab or liquid ipilimumab formulations. In addition, presence of caffeine in the formulations does not affect in vitro bioactivities of infliximab or ipilimumab. Results from this study suggest that caffeine could be a useful viscosity reducing agent that complements other traditional excipients and provides viscosity reduction to a wider range of mAb drug products.


Assuntos
Anticorpos Monoclonais , Cafeína , Composição de Medicamentos , Excipientes , Soluções , Viscosidade
8.
Physiol Meas ; 42(7)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34167102

RESUMO

Objective. A previous study has shown that a data-driven approach can significantly improve the discriminative power of transfer function analysis (TFA) used to differentiate between normal and impaired cerebral autoregulation (CA) in two groups of data. The data was collected from both healthy subjects (assumed to have normal CA) and symptomatic patients with severe stenosis (assumed to have impaired CA). However, the sample size of the labeled data was relatively small, owing to the difficulty in data collection. Therefore, in this proof-of-concept study, we investigate the feasibility of using an unsupervised learning model to differentiate between normal and impaired CA on TFA variables without requiring labeled data for learning.Approach. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), which were recorded simultaneously for approximately 10 min, were included from 148 subjects (41 healthy subjects, 31 with mild stenosis, 13 with moderate stenosis, 22 asymptomatic patients with severe stenosis, and 41 symptomatic patients with severe stenosis). Tiecks' model was used to generate surrogate data with normal and impaired CA. A recently proposed unsupervised learning model was optimized and applied to separate the normal and impaired CA for both the surrogate data and real data.Main results. It achieved 98.9% and 74.1% accuracy for the surrogate and real data, respectively.Significance. To our knowledge, this is the first attempt to employ an unsupervised data-driven approach to assess CA using TFA. This method enables the development of a classifier to determine the status of CA, which is currently lacking.


Assuntos
Pressão Arterial , Circulação Cerebrovascular , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Análise por Conglomerados , Homeostase , Humanos
9.
Artigo em Inglês | MEDLINE | ID: mdl-34167316

RESUMO

Background: The HIV-1 epidemic was mainly driven by men who have sex with men (MSM) recently in Beijing, China, with high genetic diversity. Novel recombinant strains were frequently reported at 3.4%-9.9%. It is imperative to interpret the recombinant modes and the putative transmission sources by near full-length genome (NFLG). Methods: Four individuals from the MSM population were identified as novel recombinant strains during surveillance of pretreatment drug resistance. NFLG sequences were harvested by near end-point dilution and nested PCR with two overlapping half fragments. Phylogenetic inference was performed with subtyping reference sequences and major parental strain sequences, to explore the patterns of genetic recombinant and potential sources of parent strains. The breakpoints were determined using SimPlot 3.5 to draw genome mosaic map, and the potential parental strains were confirmed by Mega 6.0 using segmental neighbor-joining trees. Results: BL19487-00 and BL1948-00 sequences were obtained from epidemiologically linked individuals and shared similar breakpoints (HXB2 nt 4,497 ± 8 to 4,722) with substitution of subtype B pol gene segment in the backbone of CRF55_01B. BL3104-00 and BL4307-00 carried seven and eight breakpoints, respectively, in the backbone of CRF65_cpx with g5 CRF01_AE substitutions. The recombinant fragments were located around gag, pol, and env genes, with vpr-tat and nef-3'-LTR genes only for BL4307-00. No transmitted drug resistance was observed with the four unique recombinant forms (URFs), except for some drug resistance associated mutations. Conclusions: The advent of URFs around CRF55_01B and CRF65_cpx identified in recent years implied that the sexual behaviors were active and the epidemic of HIV was complicated among MSM in Beijing. Molecular epidemiological surveillance and precise control should be reinforced for this population.

10.
Environ Sci Pollut Res Int ; 28(30): 41337-41350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33783709

RESUMO

Accurate estimate of riverine material fluxes in dissolved and suspended particulate forms is a fundamental issue in monitoring water environments of large basins. Here we collected sub-daily observations of dissolved pollutants (NO3--N, NH4+-N, and DOC) and daily data of suspended sediment (SS) at eight gauging stations with controlling areas varied from 694,700 to 1,705,400 km2 located in the Yangtze River basin of China, and selected optimal estimates for both dissolved and suspended particulate material fluxes from five time-averaging methods and two regression methods. The results showed that time-averaging methods generally performed better in estimating dissolved pollutants, while regression methods were more applicable for suspended particulate materials. Compared with the selected optimal methods, the conventional method generally overestimated material fluxes by 0.09-49.75% in most cases. Longer sampling interval and smaller controlling area often led to larger uncertainty in estimation and critical values of sampling interval and controlling area were generally found to be 10-20 days and 1.3 million km2 in the Yangtze River basin.


Assuntos
Rios , Poluentes Químicos da Água , China , Poeira , Monitoramento Ambiental , Poluentes Químicos da Água/análise
11.
Glob Heart ; 15(1): 72, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33150137

RESUMO

Highlights: Over half of male acute coronary syndrome patients were smokers in China.Smoking was associated with higher risk of critical cardiac symptoms at admission.Only 35.3% of smoking patients received smoking cessation interventions in China. Background: Smoking cessation is recognized as an effective and cost-effective strategy for improving the prognosis of patients with coronary heart disease. Despite this, few studies have evaluated the smoking prevalence and provision of smoking cessation interventions among patients with acute coronary syndrome (ACS) in China. Objectives: To evaluate the smoking prevalence, clinical conditions and in-hospital outcomes associated with smoking, and the provision of smoking cessation interventions among ACS patients in China. Methods: This registry study was conducted using data from the Improving Care for Cardiovascular Disease in China project, a collaborative nationwide registry of the American Heart Association and the Chinese Society of Cardiology. Our study sample comprised 92,509 ACS inpatients admitted between November 2014 and December 2018. A web-based data collection platform was used to report required data. Results: Smoking prevalence among male and female ACS patients was 52.4% and 8.0%, respectively. Patients younger than 45 years had the highest smoking rate (men: 68.0%; women: 14.9%). Compared with non-smokers, smokers had an earlier onset age of ACS and a greater proportion of severe clinical manifestations at admission, including ST-elevation myocardial infarction (67.8% versus 54.8%; p < 0.001) and substantially elevated myocardial injury markers (86.1% versus 83.0%; p < 0.001). After multivariable adjustment, smoking was associated with higher risk of critical cardiac symptoms at admission (OR = 1.14, 95% CI: 1.08-1.20; p < 0.001) and had no direct association with in-hospital outcomes (OR = 0.93, 95% CI: 0.84-1.02; p = 0.107) of ACS patients. Of 37,336 smokers with ACS, only 35.3% received smoking cessation interventions before discharge. There was wide variation in provision of smoking cessation interventions across hospitals (0%-100%). Conclusions: Smoking is highly prevalent among ACS patients in China. However, smoking cessation interventions are not widely adopted in clinical practice in China as part of formal treatment strategies for ACS patients, indicating an important target for quality improvement. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.


Assuntos
Síndrome Coronariana Aguda/prevenção & controle , Pacientes Internados , Melhoria de Qualidade , Sistema de Registros , Medição de Risco/métodos , Abandono do Hábito de Fumar/métodos , Fumar/efeitos adversos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/etiologia , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Vaccine ; 38(38): 6007-6018, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32741672

RESUMO

Smallpox, a contagious and deadly disease caused by variola virus, was eradicated by a strategy that included vaccination with vaccinia virus, a live-virus vaccine. Because the threat of bioterrorism with smallpox persists and infections with zoonotic poxvirus infections like monkeypox continue, and there may be a time when an alternative vaccine platform is needed, recombinant-subunit vaccine strategies for poxviruses have been pursued. Our prior work focused on understanding the immune responses generated to vaccine-formulations containing the virus protein L1. In this work, we examine vaccine-formulations with additional key protein targets: A33 and B5 (components of the extracellular virus) and another protein on the mature virus (A27) adjuvanted with aluminum hydroxide (AH) with and without CpG- oligonucleotide. Each vaccine was formulated to allow either adsorption or non-adsorption of the protein (and CpG) to AH. Mice given a prime and single boost produced long-lasting antibody responses. A second boost (given ~5-months after the first) further increased antibody titers. Similar to our prior findings with L1 vaccine-formulations, the most protective A33 vaccine-formulations included CpG, resulted in the generation of IgG2a-antibody responses. Unlike the prior findings with L1 (where formulations that adsorbed both the protein and the CpG to AH resulted in 100% survival after challenge and minimal weight loss), the AH-adsorption status of A33 and CpG did not play as important a role, since both AH-adsorbed and non-adsorbed groups lost weight after challenge and had similar survival. Vaccination with B5-formulations gave different results. While CpG-containing formulations were the only ones that generated IgG2a-antibody responses, the vaccine-formulation that adsorbed B5 to AH (without CpG) was as equally effective in protecting mice after challenge. These results indicate that the mechanism of how antibodies against A33 and B5 protect differ. The data also show the complexity of designing optimized vaccine-formulations containing multiple adjuvants and recombinant protein-based antigens.


Assuntos
Vacina Antivariólica , Varíola , Vírus da Varíola , Hidróxido de Alumínio , Animais , Anticorpos Antivirais , Camundongos , Camundongos Endogâmicos BALB C , Varíola/prevenção & controle , Vacinação , Vacinas de Subunidades , Vírus Vaccinia
13.
Clin Interv Aging ; 15: 111-121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099341

RESUMO

Purpose: The aim of this analysis is to describe the baseline characteristics of patients who are prescribed teriparatide for the treatment of postmenopausal osteoporosis in a real-world setting in East Asia. Patients and Methods: The Asia and Latin America Fracture Observational Study (ALAFOS) is a prospective, multinational, observational study designed to evaluate real-world use of teriparatide in the treatment of postmenopausal osteoporosis in 20 countries across Asia, Latin America, the Middle East, and Russia. This subregional analysis focuses on the East Asian subpopulation of the ALAFOS study. Here we report baseline clinical characteristics, details regarding the history of fractures, risk factors for osteoporosis, comorbidities, osteoporosis treatment, and health-related quality of life in patients enrolled in China, Hong Kong, South Korea, and Taiwan. Results: The East Asian subgroup of ALAFOS included 1136 postmenopausal women, constituting 37.5% (1136/3031) of the overall ALAFOS patient population. The mean (SD) age was 75.0 (9.6) years. The mean (SD) bone mineral density T-scores were -3.11 (1.54), -2.58 (1.11), and -2.86 (1.09) at the lumbar spine, total hip, and femoral neck, respectively; 69.6% of patients had experienced at least one fragility fracture and 40.4% had experienced ≥2 fragility fractures after 40 years of age. Overall, 63.3% of patients had used medications for osteoporosis in the past. The mean (SD) EQ-5D-5L Visual Analog Scale (VAS) score at baseline was 59.7 (20.8); the mean (SD) back pain numeric rating scale score for worst pain in the last 24 hrs was 5.2 (3.2). Conclusion: Our results indicate that patients who are prescribed teriparatide in East Asia were elderly women with severe osteoporosis, low bone mineral density, high prevalence of fractures, back pain and poor health-related quality of life. Most of the patients received teriparatide as a second-line treatment.


Assuntos
Dor nas Costas , Fraturas Ósseas , Osteoporose Pós-Menopausa , Qualidade de Vida , Teriparatida/uso terapêutico , Idoso , Dor nas Costas/epidemiologia , Dor nas Costas/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Extremo Oriente/epidemiologia , Feminino , Fraturas Ósseas/classificação , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , América Latina/epidemiologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/psicologia , Estudos Prospectivos , Fatores de Risco
14.
Environ Sci Pollut Res Int ; 26(28): 29351-29365, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396868

RESUMO

Two-stage channels are effective drainage facilities because they can decrease soil erosion and nutrient loss effectively. The lateral distribution of streamwise velocity in two-stage channels has been substantially studied. However, knowledge about the lateral distribution of sediment and phosphorus in two-stage channels with emergent vegetation on the floodplain are limited. In this work, flume experiments were conducted to investigate the relationship between current and transport of sediment and phosphorus. Results show that lateral distributions of total suspended sediment (TSS), particulate phosphorus (PP), and dissolved phosphorus (DP) are affected by the lateral variation of streamwise velocity, i.e., larger TSS and DP were found in the main channel, while larger PP appeared in the floodplain. Besides, theoretical models for the lateral distribution of TSS and DP were presented. Three models were adopted to predict the depth-averaged streamwise velocity, and corresponding results have been used to predict the TSS and DP. Comparisons indicated that with a high-precision velocity model, the newly presented analytical models can give satisfied predictions of the lateral distributions of TSS and DP.


Assuntos
Fósforo/química , Solo/química , Modelos Teóricos
15.
Artigo em Inglês | MEDLINE | ID: mdl-29559956

RESUMO

Background: Epidemiology studies have indicated an association of apolipoprotein E (ApoE) genetic polymorphism and circulating steroid hormone levels with the risk of Alzheimer's disease. The established physiologic relationship between apolipoproteins and steroid hormone indicate an important role of ApoE polymorphism in impacting the relationship between serum steroid hormones and cognition in the elderly. Study design: A total of 500 Chinese adults aged between 50 and 75 participated in this community-based cross-sectional study. Blood samples were collected in the morning for ApoE genotyping and serum parameter assessment. Cognitive performance of participants was evaluated by Montreal Cognitive Assessment test. Results: Age, gender, educational level, smoking, and physical activity levels are factors associated with cognitive performance in this older Chinese adults. Compared to the control subjects, MCI subjects demonstrated higher serum total cholesterol, HDL-C, and estradiol status (P < 0.05). ApoE genotype difference of serum lipid profile was observed with a relatively higher mean serum triglyceride levels in ApoE2 and ApoE4 carriers (P < 0.05), and lower mean serum HDL-C level in ApoE4 carriers (P < 0.05). Memory and delayed recall ability was serum estradiol level related; and subjects with higher circulating estradiol concentration exhibited lower memory and delayed recall ability (P < 0.05). The association of serum estradiol and cortisol concentration with cognitive performance was ApoE genotypes dependent. Poor cognitive performance was observed in ApoE2 and ApoE4 carriers with higher serum estradiol level (P < 0.05). Moreover, ApoE2 and ApoE4 carriers with higher serum cortisol status demonstrated decreased language ability (P < 0.05). Multiple logistic regression analysis indicates that subjects with higher serum estradiol status may have an increased risk for MCI [OR = 2.004, 95% confidence interval (CI): 1.135, 3.540; P = 0.017]. ApoE2 carriers with higher serum steroid levels may be potentially predisposed to an increased risk of MCI (OR = 3.353; 95% CI: 1.135, 9.907; P = 0.029). Conclusion: Cognitive outcomes in older Chinese adults are associated with serum steroid hormone status. Higher serum steroid levels in ApoE2 carriers might pose an increased risk of MCI in the elderly.

16.
PeerJ ; 5: e3450, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28630804

RESUMO

Some evidence suggests that bone health can be regulated by gut microbiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP) patients, osteopenia (ON) patients and normal controls (NC). We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA) could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples (p < 0.05), Gemmatimonadetes and Chloroflexi were significantly different between OP and NC group as well as between ON and NC group (p < 0.01). A total of 21 genera with proportions above 1% were detected and Bacteroides accounted for the largest proportion in all samples. The Blautia, Parabacteroides and Ruminococcaceae genera differed significantly between the OP and NC group (p < 0.05). Linear discriminant analysis (LDA) results showed one phylum community and seven phylum communities were enriched in ON and OP, respectively. Thirty-five genus communities, five genus communities and two genus communities were enriched in OP, ON and NC, respectively. The results of this study indicate that gut microbiota may be a critical factor in osteoporosis development, which can further help us search for novel biomarkers of gut microbiota in OP and understand the interaction between gut microbiota and bone health.

17.
J Pharm Sci ; 103(1): 140-51, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24282078

RESUMO

To improve the effectiveness of the polio vaccination campaign, improvements in the thermal stability of the vaccine are being investigated. Here, inactivated polio vaccine, serotype 3 (IPV3) was characterized via a number of biophysical techniques. The size was characterized by transmission electronic microscopy and light scattering. The capsid protein conformation was evaluated by intrinsic fluorescence and circular dichroism (CD), and the D-antigen content by enzyme-linked immunosorbent assay (ELISA). The pH thermal stability of IPV3 (pH 3.0-8.0; 10°C-87.5°C) was evaluated by fluorescence, CD, and static light scattering. The transition temperatures reflect the responses, respectively, of tertiary structure, secondary structure, and size to applied thermal stress. The data were summarized as empirical phase diagrams, and the most stable conditions were found to be pH 7.0 with temperature lower than 40°C. CD detected a higher transition temperature for capsid protein than that for RNA. The effects of certain excipients on IPV3 thermal stability and antigen content were evaluated. The results of their effects, based on intrinsic fluorescence and ELISA, were in good agreement, suggesting the feasibility of applying intrinsic fluorescence as a high-throughput tool for formulation development. The study improves the understanding of IPV3 thermal stability, and provides a starting point for future formulation development of IPV3 and other serotypes.


Assuntos
Proteínas do Capsídeo/química , Vacinas Virais/química , Antígenos Virais/imunologia , Química Farmacêutica/métodos , Excipientes/química , Concentração de Íons de Hidrogênio , Poliomielite/imunologia , Poliovirus/imunologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Temperatura de Transição
18.
J Pharm Sci ; 102(12): 4305-14, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24129946

RESUMO

Chikungunya virus (CHIKV) is an alphavirus that infects millions of people every year, especially in the developing world. The selective expression of recombinant CHIKV capsid and envelope proteins results in the formation of self-assembled virus-like particles (VLPs) that have been shown to protect nonhuman primates against infection from multiple strains of CHIKV. This study describes the characterization, excipient screening, and optimization of CHIKV VLP solution conditions toward the development of a stable parenteral formulation. The CHIKV VLPs were found to be poorly soluble at pH 6 and below. Circular dichroism, intrinsic fluorescence, and static and dynamic light scattering measurements were therefore performed at neutral pH, and results consistent with the formation of molten globule structures were observed at elevated temperatures. A library of generally recognized as safe excipients was screened for their ability to physically stabilize CHIKV VLPs using a high-throughput turbidity-based assay. Sugars, sugar alcohols, and polyanions were identified as potential stabilizers and the concentrations and combinations of select excipients were optimized. The effects of polyanions were further studied, and while all polyanions tested stabilized CHIKV VLPs against aggregation, the effects of polyanions on conformational stability varied.


Assuntos
Vírus Chikungunya/química , Excipientes/química , Polímeros/química , Vacinas de Partículas Semelhantes a Vírus/química , Infecções por Alphavirus/prevenção & controle , Infecções por Alphavirus/virologia , Animais , Febre de Chikungunya , Dicroísmo Circular , Luz , Concentração Osmolar , Tamanho da Partícula , Estabilidade Proteica , Espalhamento de Radiação
19.
Vaccine ; 31(2): 319-26, 2013 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-23153450

RESUMO

The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness against the intentional or accidental release of smallpox. Ongoing research on future generation smallpox vaccines is providing key insights into protective immune responses as well as important information about subunit-vaccine design strategies. For protein-based recombinant subunit vaccines, the formulation and stability of candidate antigens with different adjuvants are important factors to consider for vaccine design. In this work, a non-tagged secreted L1-protein, a target antigen on mature virus, was expressed using recombinant baculovirus technology and purified. To identify optimal formulation conditions for L1, a series of biophysical studies was performed over a range of pH and temperature conditions. The overall physical stability profile was summarized in an empirical phase diagram. Another critical question to address for development of an adjuvanted vaccine was if immunogenicity and protection could be affected by the interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a second adjuvant, CpG. We thus designed a series of vaccine formulations with different binding interactions between the L1 and the two adjuvants, and then performed a series of vaccination-challenge experiments in mice including measurement of antibody responses and post-challenge weight loss and survival. We found that better humoral responses and protection were conferred with vaccine formulations when the L1-protein was adsorbed to Alhydrogel. These data demonstrate that designing vaccine formulation conditions to maximize antigen-adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity and protection.


Assuntos
Hidróxido de Alumínio/imunologia , Proteínas de Ligação a DNA/imunologia , Vírus Vaccinia/imunologia , Vaccinia/prevenção & controle , Proteínas do Core Viral/imunologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adsorção , Hidróxido de Alumínio/química , Animais , Formação de Anticorpos , Proteínas de Ligação a DNA/química , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Poxviridae/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Vacina Antivariólica/química , Vacina Antivariólica/imunologia , Vacinas de Subunidades/imunologia , Vaccinia/imunologia , Proteínas do Core Viral/química
20.
PLoS One ; 7(9): e45898, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029300

RESUMO

BACKGROUND: During the 2009 pandemic influenza H1N1 (2009) virus (pH1N1) outbreak, school students were at an increased risk of infection by the pH1N1 virus. However, the estimation of the attack rate showed significant variability. METHODS: Two school outbreaks were investigated in this study. A questionnaire was designed to collect information by interview. Throat samples were collected from all the subjects in this study 6 times and sero samples 3 times to confirm the infection and to determine viral shedding. Data analysis was performed using the software STATA 9.0. FINDINGS: The attack rate of the pH1N1 outbreak was 58.3% for the primary school, and 52.9% for the middle school. The asymptomatic infection rates of the two schools were 35.8% and 37.6% respectively. Peak virus shedding occurred on the day of ARI symptoms onset, followed by a steady decrease over subsequent days (p = 0.026). No difference was found either in viral shedding or HI titer between the symptomatic and the asymptomatic infectious groups. CONCLUSIONS: School children were found to be at a high risk of infection by the novel virus. This may be because of a heightened risk of transmission owing to increased mixing at boarding school, or a lack of immunity owing to socio-economic status. We conclude that asymptomatically infectious cases may play an important role in transmission of the pH1N1 virus.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Pandemias , Instituições Acadêmicas , Adolescente , Infecções Assintomáticas/epidemiologia , Criança , China/epidemiologia , Surtos de Doenças , Feminino , Humanos , Influenza Humana/virologia , Masculino , Fatores de Risco , Inquéritos e Questionários , Carga Viral , Eliminação de Partículas Virais
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