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1.  Identification of Susceptibility Variants in ADIPOR1 Gene Associated with Type 2 Diabetes, Coronary Artery Disease and the Comorbidity of Type 2 Diabetes and Coronary Artery Disease 
PLoS ONE  2014;9(6):e100339.
Objective
Adiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the “common soil” hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population.
Methods
Our multi-disease comparison study enrolled 657 subjects, including 165 with T2D, 173 with CAD, 174 with both T2D and CAD (T2D+CAD), and 145 local healthy controls. Six ADIPOR1 single nucleotide polymorphisms (SNPs) were genotyped and their association with disease risk was analyzed.
Results
Multi-case-control comparison identified two ADIPOR1 variants: rs3737884-G, which was simultaneously associated with an increased risk of T2D, CAD, and T2D+CAD (P-value range, 9.80×10−5−6.30×10−4; odds ratio (OR) range: 1.96–2.42) and 16850797-C, which was separately associated with T2D and T2D+CAD (P-value range: 0.007–0.014; OR range: 1.71–1.77). The risk genotypes of both rs3737884 and 16850797 were consistently associated with common metabolic phenotypes in all three diseases (P-value range: 4.81×10−42−0.001). We observed an increase in the genetic dose-dependent cumulative risk with increasing risk allele numbers in T2D, CAD and T2D+CAD (P trend from 1.35×10−5−0.002).
Conclusions
Our results suggest that ADIPOR1 risk polymorphisms are a strong candidate for the “common soil” hypothesis and could partially contribute to disease susceptibility to T2D, CAD, and T2D with CAD in the Northern Han Chinese population.
doi:10.1371/journal.pone.0100339
PMCID: PMC4072681  PMID: 24967709
2.  Evaluation of Finnish Diabetes Risk Score in Screening Undiagnosed Diabetes and Prediabetes among U.S. Adults by Gender and Race: NHANES 1999-2010 
PLoS ONE  2014;9(5):e97865.
Objective
To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and race.
Methods
This cross-sectional analysis included participants (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 1999–2010. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes and prediabetes were calculated for FINDRISC by gender and race/ethnicity.
Results
Among the 20,633 adults (≥20 years), 49.8% were women and 53.0% were non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was 4.1% and 35.6%, respectively. FINDRISC was positively associated with the prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03 for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67 for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity = 0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for men and 10 (sensitivity = 0.69) for women for detecting prediabetes.
Conclusions
FINDRISC is a simple and non-invasive screening tool to identify individuals at high risk for diabetes in the U.S. adults.
doi:10.1371/journal.pone.0097865
PMCID: PMC4031122  PMID: 24852786
3.  A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting 
Background
Humans vary in their susceptibility to acquiring Staphylococcus aureus infection, and research suggests that there is a genetic basis for this variability. Several recent genome-wide association studies (GWAS) have identified variants that may affect susceptibility to infectious diseases, demonstrating the potential value of GWAS in this arena.
Methods
We conducted a GWAS to identify common variants associated with acquisition of S. aureus bacteremia (SAB) resulting from healthcare contact. We performed a logistic regression analysis to compare patients with healthcare contact who developed SAB (361 cases) to patients with healthcare contact in the same hospital who did not develop SAB (699 controls), testing 542,410 SNPs and adjusting for age (by decade), sex, and 6 significant principal components from our EIGENSTRAT analysis. Additionally, we evaluated the joint effect of the host and pathogen genomes in association with severity of SAB infection via logistic regression, including an interaction of host SNP with bacterial genotype, and adjusting for age (by decade), sex, the 6 significant principal components, and dialysis status. Bonferroni corrections were applied in both analyses to control for multiple comparisons.
Results
Ours is the first study that has attempted to evaluate the entire human genome for variants potentially involved in the acquisition or severity of SAB. Although this study identified no common variant of large effect size to have genome-wide significance for association with either the risk of acquiring SAB or severity of SAB, the variant (rs2043436) most significantly associated with severity of infection is located in a biologically plausible candidate gene (CDON, a member of the immunoglobulin family) and may warrant further study.
Conclusions
The genetic architecture underlying SAB is likely to be complex. Future investigations using larger samples, narrowed phenotypes, and advances in both genotyping and analytical methodologies will be important tools for identifying causative variants for this common and serious cause of healthcare-associated infection.
doi:10.1186/1471-2334-14-83
PMCID: PMC3928605  PMID: 24524581
Genomics; Genome-wide association study; Case–control study; Staphylococcus aureus; Bacteremia; Gram-positive bacterial infections; Polymorphism, single-nucleotide; Infections; Nosocomial; Cross infection
4.  Intraspecific Scaling of the Resting and Maximum Metabolic Rates of the Crucian Carp (Carassius auratus) 
PLoS ONE  2013;8(12):e82837.
The question of how the scaling of metabolic rate with body mass (M) is achieved in animals is unresolved. Here, we tested the cell metabolism hypothesis and the organ size hypothesis by assessing the mass scaling of the resting metabolic rate (RMR), maximum metabolic rate (MMR), erythrocyte size, and the masses of metabolically active organs in the crucian carp (Carassius auratus). The M of the crucian carp ranged from 4.5 to 323.9 g, representing an approximately 72-fold difference. The RMR and MMR increased with M according to the allometric equations RMR = 0.212M0.776 and MMR = 0.753M0.785. The scaling exponents for RMR (br) and MMR (bm) obtained in crucian carp were close to each other. Thus, the factorial aerobic scope remained almost constant with increasing M. Although erythrocyte size was negatively correlated with both mass-specific RMR and absolute RMR adjusted to M, it and all other hematological parameters showed no significant relationship with M. These data demonstrate that the cell metabolism hypothesis does not describe metabolic scaling in the crucian carp, suggesting that erythrocyte size may not represent the general size of other cell types in this fish and the metabolic activity of cells may decrease as fish grows. The mass scaling exponents of active organs was lower than 1 while that of inactive organs was greater than 1, which suggests that the mass scaling of the RMR can be partly due to variance in the proportion of active/inactive organs in crucian carp. Furthermore, our results provide additional evidence supporting the correlation between locomotor capacity and metabolic scaling.
doi:10.1371/journal.pone.0082837
PMCID: PMC3869722  PMID: 24376588
5.  Pathways to psychiatric care in urban north China: a general hospital based study 
Background
Pathway studies highlight the help-seeking behaviors of patients with physical and mental illnesses. A number of studies in this field have been completed in various parts of the world. The purpose of this study is to explore the characteristics of the help-seeking pathways of patients with mental illness from urban north China at Mental Health Professional (MHP).
Methods
The pathway diagrams, which accounted for more than five percent of patients, were documented for 441 subjects using the translated version of the World Health Organization (WHO) pathway encounter form. The patterns and durations of care-seeking were analyzed in different diagnostic groups. The χ2-test and the Mann-Whitney U test were employed, as needed.
Results
Respondents visited the MHP through a variety of pathways. Approximately three-quarters of the patients took an indirect pathway (74.8% vs 25.2%, χ2 = 108.8, p < 0.0001), and on average, each patient consulted 3.4 caregivers. The vast majority of patients first visited local tertiary general hospitals (56.4% vs 4.1%, χ2 = 138.3, p < 0.0001) or local secondary general hospitals (24.8% vs 4.1%, χ2 = 40.96, p < 0.0001). However, only 9.6% of patients were diagnosed with mental disorders for the patients who first visited non-psychiatric hospitals. Of the patients who first contacted with psychiatry hospital, 55.6% received a professional diagnosis and finally reached the MHP because of the poor treatment or high-cost medical care.
Conclusions
The majority of patients seek other pathways than to go to MHP directly and this may be due to stigma, and/or lack of knowledge. The study gives emphasis on the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders in the community health centers, the general hospitals system and by private practitioners. The pathway described by this study may be helpful while preparing mental health programs in the future.
doi:10.1186/1752-4458-7-22
PMCID: PMC3852166  PMID: 24020825
Help-seeking pathways; Psychiatric care; Patients with mental illness; Mental health professional; Urban north China
6.  Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model 
PLoS ONE  2013;8(4):e60463.
Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bacterial and host characteristics as compared to V. Mice were injected with S. aureus USA300, and then intravenously treated with 25 mg/kg of either L or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced in both L and V-treated mice compared to untreated mice but the reduction did not reach the statistical significance [P = 0.12 for L; P = 0.70 for V). PVL was significantly reduced in L-treated mice compared to untreated mice (P = 0.02). However the reduction of in vivo PVL did not reach the statistical significance in V- treated mice compared to untreated mice (P = 0.27). Both antibiotics significantly reduced IL-1β production [P = 0.001 for L; P = 0.006 for V]. IL-6 was significantly reduced with L but not V antibiotic treatment [P<0.001 for L; P = 0.11 for V]. Neither treatment significantly reduced production of TNF-α. Whole-blood gene expression profiling showed no significant effect of L and V on uninfected mice. In S. aureus-infected mice, L altered the expression of a greater number of genes than V (95 vs. 42; P = 0.001). Pathway analysis for the differentially expressed genes identified toll-like receptor signaling pathway to be common to each S. aureus-infected comparison. Expression of immunomodulatory genes like Cxcl9, Cxcl10, Il1r2, Cd14 and Nfkbia was different among the treatment groups. Glycerolipid metabolism pathway was uniquely associated with L treatment in S. aureus infection. This study demonstrates that, as compared to V, treatment with L is associated with reduced levels of toxin production, differences in host inflammatory response, and distinct host gene expression characteristics in MRSA sepsis.
doi:10.1371/journal.pone.0060463
PMCID: PMC3614971  PMID: 23565251
7.  Comparison of the body proximate compositions of juvenile bronze gudgeon (Coreius heterodon) and largemouth bronze gudgeon (C. guichenoti) in the upstream region of the Yangtze River 
SpringerPlus  2013;2:75.
The body proximate compositions were assessed in juvenile Coreius heterodon and C. guichenoti from the upstream of the Yangtze River. The migratory C. guichenoti has a higher lipid content (FAT) than the residential C. heterodon. FAT of C. guichenoti showed an interesting pattern of increase, where FAT increased up rapidly and then leveled off as body mass (M) increased above 6.5 g, suggesting that the lipid concentration reaches an upper limit of deposition. In both species, FAT of the smaller individuals was lower than protein content (PRO), but FAT increased more rapidly than PRO as the fish grew. This indicates that more energy was allocated to protein synthesis than lipid in the smaller fish, with an energy allocation shift from protein synthesis to lipid storage as the fish grew. Strong relationships between both FAT and energy content (E) and water content (WAT) were found in both species, suggesting strong predictive power for future application. However, different models for the two species should be used to predict FAT or E by WAT.
doi:10.1186/2193-1801-2-75
PMCID: PMC3599173  PMID: 23518873
Body size; Water content; Lipid content; Energy content; Bronze gudgeon
8.  Gene Expression-Based Classifiers Identify Staphylococcus aureus Infection in Mice and Humans 
PLoS ONE  2013;8(1):e48979.
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host’s inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.
doi:10.1371/journal.pone.0048979
PMCID: PMC3541361  PMID: 23326304
9.  Older Adults with HIV/AIDS in Rural China 
The Open AIDS Journal  2013;7:51-57.
Although the number of older people living with HIV/AIDS (PLWHA) has increased substantially, few studies have focused on older PLWHA in developing countries. Based on a sample of 866 rural PLWHA in Henan, Anhui and Yunnan provinces in China, this study compares the characteristics of PLWHA aged 50 or older (n=185) with younger PLWHA (n=681). Most of the older PLWHA were female (n=112), illiterate, married and at the clinical stage of HIV. Over 90% of older people with HIV/AIDS lived in Henan and Anhui provinces. The severe epidemic in Henan and Anhui provinces was caused by commercial blood and plasma donation. Older PLWHA were less educated, received less social support and were more likely to live alone than younger PLWHA. The results underline the importance of developing programs and policy initiatives targeted at older people infected with HIV/AIDS. The policy and program recommendations include using a gender sensitive strategy, designing specific AIDS education and prevention programs suitable for low-literacy older adults and social support interventions for older PLWHA.
doi:10.2174/1874613601307010051
PMCID: PMC3893720  PMID: 24454590
Asia; HIV/AIDS; human immunodeficiency virus infection/acquired immunodeficiency syndrome; older adults; older people; rural China.
10.  Presence of Genes Encoding Panton-Valentine Leukocidin Is Not the Primary Determinant of Outcome in Patients with Hospital-Acquired Pneumonia Due to Staphylococcus aureus 
Journal of Clinical Microbiology  2012;50(3):848-856.
The impact of Panton-Valentine leukocidin (PVL) on the outcome in Staphylococcus aureus pneumonia is controversial. We genotyped S. aureus isolates from patients with hospital-acquired pneumonia (HAP) enrolled in two registrational multinational clinical trials for the genetic elements carrying pvl and 30 other virulence genes. A total of 287 isolates (173 methicillin-resistant S. aureus [MRSA] and 114 methicillin-susceptible S. aureus [MSSA] isolates) from patients from 127 centers in 34 countries for whom clinical outcomes of cure or failure were available underwent genotyping. Of these, pvl was detected by PCR and its product confirmed in 23 isolates (8.0%) (MRSA, 18/173 isolates [10.4%]; MSSA, 5/114 isolates [4.4%]). The presence of pvl was not associated with a higher risk for clinical failure (4/23 [17.4%] versus 48/264 [18.2%]; P = 1.00) or mortality. These findings persisted after adjustment for multiple potential confounding variables. No significant associations between clinical outcome and (i) presence of any of the 30 other virulence genes tested, (ii) presence of specific bacterial clone, (iii) levels of alpha-hemolysin, or (iv) delta-hemolysin production were identified. This study suggests that neither pvl presence nor in vitro level of alpha-hemolysin production is the primary determinant of outcome among patients with HAP caused by S. aureus.
doi:10.1128/JCM.06219-11
PMCID: PMC3295120  PMID: 22205797
11.  Glycosylated Hemoglobin in Relationship to Cardiovascular Outcomes and Death in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis 
PLoS ONE  2012;7(8):e42551.
Background
Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes.
Methodology/Principal Findings
We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2–16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes.
Conclusions/Significance
Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.
doi:10.1371/journal.pone.0042551
PMCID: PMC3415427  PMID: 22912709
12.  Panton-Valentine Leukocidin Is Not the Primary Determinant of Outcome for Staphylococcus aureus Skin Infections: Evaluation from the CANVAS Studies 
PLoS ONE  2012;7(5):e37212.
The impact of Panton-Valentine leukocidin (PVL) on the severity of complicated skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome and PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates from patients enrolled in two large, multinational phase three clinical trials assessing ceftaroline fosamil for the treatment of cSSSI (the CANVAS 1 and 2 programs). Isolates from all microbiologically evaluable patients with monomicrobial MRSA or MSSA infections (n = 473) were genotyped by PCR for pvl and underwent pulsed-field gel electrophoresis (PFGE). Genes encoding pvl were present in 266/473 (56.2%) isolates. Infections caused by pvl-positive S. aureus were associated with younger patient age, North American acquisition, and presence of major abscesses (P<0.001 for each). Cure rates of patients infected with pvl-positive and pvl-negative S. aureus were similar overall (93.6% versus 92.8%; P = 0.72), and within MRSA-infected (94.5% vs. 93.1%; P = 0.67) and MSSA-infected patients (92.2% vs. 92.7%; P = 1.00). This finding persisted after adjustment for multiple patient characteristics. Outcomes were also similar when USA300 PVL+ and non-USA300 PVL+ infections were compared. The results of this contemporary, international study suggest that pvl presence was not the primary determinant of outcome in patients with cSSSI due to either MRSA or MSSA.
doi:10.1371/journal.pone.0037212
PMCID: PMC3356380  PMID: 22623995
13.  Decentralization of the provision of health services to people living with HIV/AIDS in rural China: the case of three counties 
This study is based on a large-scale household survey and in-depth interviews of key informants that was conducted in villages in three counties of two provinces in China. We assess the new decentralized service provision system for people living with HIV/AIDS in rural populations in China. Since 2003, new social assistance schemes, and, more importantly, decentralization of routine treatment and care to community health stations, were progressively implemented in rural areas most affected by the HIV/AIDS epidemic. Though some problems remain, such as persistent discrimination towards infected patients and the lack of sufficient training of medical staff, the new decentralized pattern of service provision has lowered barriers to health access and alleviated economic pressure on affected households.
doi:10.1186/1478-4505-9-9
PMCID: PMC3045992  PMID: 21310093
14.  Impact of HIV/AIDS on Social Relationships in Rural China 
The Open AIDS Journal  2011;5:67-73.
Social support promotes greater medical compliance, better immune system functioning and slows the progress of HIV/AIDS. One in every 50 People Living With HIV/AIDS (PLWHA) is Chinese, yet little is known about the impact of HIV/AIDS on social relationships in China. This study compares the characteristics of those who report that HIV/AIDS had a substantial impact versus a modest impact on their social relationships. We obtained data from a survey of 866 PLWHA in rural China, which was conducted in 2006-2007 in the three Chinese provinces with the highest prevalence of HIV/AIDS. Chi-square test and multiple logistic regression were performed. The analysis shows that PLWHA who had full-blown AIDS (OR= 1.53; 95% CI=1.09-2.13) and those who were poor (OR=2.19; 95% CI=1.52-3.16) reported greater impact on their social relationships. The results lay a solid foundation for designing effective policy initiatives and intervention programs aimed at alleviating the impact of HIV/AIDS on social relationships and improving the quality of life of PLWHA.
doi:10.2174/1874613601105010067
PMCID: PMC3141326  PMID: 21792384
HIV/AIDS; China; social relationships; developing world; social support.

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