First Qualification Study of Serum Biomarkers as Indicators of Total Body Burden of Osteoarthritis

Background

Osteoarthritis (OA) is a debilitating chronic multijoint disease of global proportions. OA presence and severity is usually documented by x-ray imaging but whole body imaging is impractical due to radiation exposure, time and cost. Systemic (serum or urine) biomarkers offer a potential alternative method of quantifying total body burden of disease but no OA-related biomarker has ever been stringently qualified to determine the feasibility of this approach. The goal of this study was to evaluate the ability of three OA-related biomarkers to predict various forms or subspecies of OA and total body burden of disease.

Methodology/Principal Findings

Female participants (461) with clinical hand OA underwent radiography of hands, hips, knees and lumbar spine; x-rays were comprehensively scored for OA features of osteophyte and joint space narrowing. Three OA-related biomarkers, serum hyaluronan (sHA), cartilage oligomeric matrix protein (sCOMP), and urinary C-telopeptide of type II collagen (uCTX2), were measured by ELISA. sHA, sCOMP and uCTX2 correlated positively with total osteophyte burden in models accounting for demographics (age, weight, height): R² = 0.60, R² = 0.47, R² = 0.51 (all p<10⁻⁶); sCOMP correlated negatively with total joint space narrowing burden: R² = 0.69 (p<10⁻⁶). Biomarkers and demographics predicted 35–38% of variance in total burden of OA (total joint space narrowing or osteophyte). Joint size did not determine the contribution to the systemic biomarker concentration. Biomarker correlation with disease in the lumbar spine resembled that in the rest of the skeleton.

Conclusions/Significance

We have suspected that the correlation of systemic biomarkers with disease has been hampered by the inability to fully phenotype the burden of OA in a patient. These results confirm the hypothesis, revealed upon adequate patient phenotyping, that systemic joint tissue concentrations of several biomarkers can be quantitative indicators of specific subspecies of OA and of total body burden of disease.     

Mitochondrial DNA (mtDNA) Haplogroups Influence the Progression of Knee Osteoarthritis. Data from the Osteoarthritis Initiative (OAI)

Objective

To evaluate the influence of the mtDNA haplogroups on knee osteoarthritis progression in Osteoarthritis Initiative (OAI) participants through longitudinal data from radiographs and magnetic resonance imaging (MRI).

Methods

Four-year knee osteoarthritis progression was analyzed as increase in Kellgren and Lawrence (KL) grade, in addition to increase in OARSI atlas grade for joint space narrowing (JSN), osteophytes and subchondral sclerosis in the tibia medial compartment of 891 Caucasian individuals from the progression subcohort. The influence of the haplogroups on the rate of structural progression was also assessed as the four-year change in minimum joint space width (mJSW in millimetres) in both knees of (n = 216) patients with baseline unilateral medial-tibiofemoral JSN. Quantitative cartilage measures from longitudinal MRI data were those related to cartilage thickness and volume with a 24 month follow-up period (n = 381).

Results

During the four-year follow-up period, knee OA patients with the haplogroup T showed the lowest increase in KL grade (Hazard Risk [HR] = 0.499; 95% Confidence Interval [CI]: 0.261–0.819; p<0.05) as well as the lowest cumulative probability of progression for JSN (HR = 0.547; 95% CI: 0.280–0.900; p<0.05), osteophytes (HR = 0.573; 95% CI: 0.304–0.893; p<0.05) and subchondral sclerosis (HR = 0.549; 95% CI: 0.295–0.884; p<0.05). They also showed the lowest decline in mJSW (standardized response means (SRM) = −0.39; p = 0.037) in those knees without baseline medial JSN (no-JSN knees). Normalized cartilage volume loss was significantly lower in patients carrying the haplogroup T at medial tibia femoral (SRM = −0.33; p = 0.023) and central medial femoral (SRM = −0.27; p = 0.031) compartments. Cartilage thickness loss was significantly lower in carriers of haplogroup T at central medial tibia-femoral (SRM = −0.42; p = 0.011), medial tibia femoral (SRM = −0.32; p = 0.018), medial tibia anterior (SRM = +0.31; p = 0.013) and central medial femoral (SRM = −0.19; p = 0.013) compartments.

Conclusions

Mitochondrial genome seems to play a role in the progression of knee osteoarthritis. mtDNA variation could improve identification of patients predisposed to faster or severe progression of the disease.     

Magnetic Resonance Imaging of Osteophytic,Chondral, and Subchondral Structures in a Surgically-Induced Osteoarthritis Rabbit Model

Objective

This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model.

Methods

The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons.

Results

The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05–0.15 to 1.15–1.30 to 1.90–1.97 to 3.00–3.35 at each successive time point, respectively (p<0.05). Subchondral bone lesions progressed from a grade of 0.00 to 0.78–0.90 to 1.27–1.58 to 1.95–2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87–1.06 to 1.24–1.87 to 2.21–3.21 at each successive time point, respectively (p = 0.000).

Conclusions

Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.     

Sputum Inflammatory Profile Before and After Specific Inhalation Challenge in Individuals with Suspected Occupational Asthma

Background

The aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B₄ (LTB₄) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular-weight (LMW) agents.

Material and Methods

Fifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB₄ and a 10 Th1/Th2 cytokines were measured in sputum supernatant.

Results

Thirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB₄ level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146).

Conclusion

When conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents.     

Association of SMAD7 rs12953717 Polymorphism with Cancer: A Meta-Analysis

Background

Accumulating evidence has suggested that Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism might be related to cancer risk. However, epidemiologic findings have been inconsistent. We therefore performed a meta-analysis to clarify the association between the SMAD7 rs12953717 polymorphism and cancer risk.

Methods

A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and cancer risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

A total of 14 case-control studies, including 16928 cases and 14781 controls, were included in the present meta-analysis. The overall results showed that the variant genotypes were associated with a significantly increased risk of all cancer types (homozygote comparison, OR = 1.23, 95%CI = 1.10–1.38, P<0.01; heterozygote comparison, OR = 1.12, 95%CI = 1.02–1.22, P = 0.02; recessive model, OR = 1.17, 95%CI = 1.07–1.29, P<0.01; dominant model, OR = 1.15, 95%CI = 1.06–1.25, P<0.01; allelic model, OR = 1.12, 95%CI = 1.06–1.18, P<0.01). Further sensitivity analysis confirmed the significant association. In the subgroup analysis by ethnicity, SMAD7 rs12953717 polymorphism was significantly associated with cancer risk in both Caucasians and Asians. In the subgroup analysis by cancer types, SMAD7 rs12953717 polymorphism was significantly associated with colorectal cancer.

Conclusions

Our investigations demonstrate that rs12953717 polymorphism is associated with the susceptibility of cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.     

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background

There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.

Methods

Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.

Results

Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV₁] <80% of predicted value). The mean FEV₁ decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV₁>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV₁ decline. Initial FEV₁>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).

Conclusions

NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.     

Age at Menarche and Natural Menopause and Number of Reproductive Years in Association with Mortality: Results from a Median Follow-Up of 11.2 Years among 31,955 Naturally Menopausal Chinese Women

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women''s Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (P_trend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (P_trend  = 0.03) and diabetes (P_trend = 0.02) but lower risk of mortality from respiratory system cancer (P_trend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (P_trend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.     

The MDM2 309T>G Polymorphism and Ovarian Cancer Risk: A Meta-Analysis of 1534 Cases and 2211 Controls

Background

Recently, there have been a number of studies on the association between MDM2 (Murine Double Minute 2) 309 polymorphism and ovarian cancer risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between MDM2 309 polymorphism and the risk of ovarian cancer.

Methods

A meta-analysis was performed to examine the association between MDM2 309T>G polymorphism and ovarian cancer risk. Odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis.

Results

Our publication search identified a total of 6 studies with 1534 cases and 2211 controls. No significant association was found between MDM2 309T>G polymorphism and ovarian cancer risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Asian subgroup (G vs. T OR = 0.774, 95% CI = 0.628–0.955, P = 0.017, P _het = 0.327; GG vs. TT: OR = 0.601, 95% CI = 0.395–0.914, P = 0.017, P _het = 0.417; dominant model TG+GG vs. TT: OR = 0.661, 95% CI = 0.468–0.934, P = 0.019, P _het = 0.880), and no significant association in any genetic models among Caucasians was observed.

Conclusions

This meta-analysis provides evidence for the association between MDM2 309 polymorphism and ovarian cancer risk, supporting the hypothesis that MDM2 SNP309 G allele acts as an important ovarian cancer protective factor in Asians but not in Caucasians.     

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

Purpose

Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.

Methods

This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).

Results

Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: P_interaction = 0.002; Gene-sex: P_interaction = 0.002; Gene-smoking: P_interaction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.

Conclusion

These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.     

Role of mtDNA Haplogroups in the Prevalence of Osteoarthritis in Different Geographic Populations: A Meta-Analysis

Background

Osteoarthritis (OA) is the most common form of arthritis and has become an increasingly important public-health problem. However, the pathogenesis of OA is still unclear. In recent years, its correlation with mtDNA haplogroups attracts much attention. We aimed to perform a meta-analysis to investigate the association between mtDNA haplogroups and OA.

Methods

Published English or Chinese literature from PubMed, Web of Science, SDOS, and CNKI was retrieved up until April 15, 2014. Case-control or cohort studies that detected the frequency of mtDNA haplogroups in OA patients and controls were included. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) assessment. A meta-analysis was conducted to calculate pooled odds ratio (OR) with 95% confidence interval (CI) through the random or fixed effect model, which was selected based on the between-study heterogeneity assessed by Q test and I² test. Subgroup analysis was performed to explore the origin of heterogeneity.

Results

A total of 6 case-control studies (10590 cases and 7161 controls) with an average NOS score of 6.9 were involved. For the analysis between mtDNA haplogroup J and OA, random model was selected due to high heterogeneity. No significant association was found initially (OR = 0.73, 95%CI: 0.52–1.03), however, once any study from UK population was removed the association emerged. Further subgroup analysis demonstrated that there was a significant association in Spain population (OR = 0.57, 95%CI: 0.46–0.71), but not in UK population. Also, subgroup analysis revealed that there was a significant correlation between cluster TJ and OA in Spain population (OR = 0.70, 95%CI: 0.58–0.84), although not in UK population. No significant correlation was found between haplogroup T/cluster HV/cluster KU and OA.

Conclusions

Our current meta-analysis suggests that mtDNA haplogroup J and cluster TJ correlate with the risk of OA in Spanish population, but the associations in other populations require further investigation.     

A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

Background

Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.

Objective

We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV₁) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.

Methods

DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV₁ was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.

Results

Two SNPs were found to be significant (P<6.29×10⁻⁵), including rs1910047 (P = 3.07×10⁻⁵, FDR = 0.0778) and rs9469089 (P = 6.19×10⁻⁵, FDR = 0.0967), as well as other eight suggestive (P<5×10⁻⁴) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV₁ decline occurred (P _trend = 3.01×10⁻¹⁸). However, the association was different among age subgroups (P = 7.11×10⁻⁶) and endotoxin subgroups (P = 1.08×10⁻²). Functional network analysis illustrates potential biological connections of all interacted genes.

Conclusions

Genetic variants together with environmental factors interact to affect the rate of FEV₁ decline in cotton textile workers.     

Association between Glutathione S-Transferase T1 Null Genotype and Gastric Cancer Risk: A Meta-Analysis of 48 Studies

Background

Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies.

Methods

We searched in the Pubmed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTT1 null genotype and gastric cancer risk. The pooled odds ratio (OR) and its 95% confidence interval (95%CI) was calculated to assess the strength of the association. A total of 48 studies with a total of 24,440 individuals were ultimately eligible for meta-analysis.

Results

Overall, GSTT1 null genotype was significantly associated with increased risk of gastric cancer (Random-effect OR = 1.23, 95%CI 1.13–1.35, P _OR <0.001, I² = 45.5%). Significant association was also found in Caucasians, East Asians, and Indians (P _Caucasians = 0.010; P _{East Asians} = 0.003; P _Indians = 0.017). After adjusting for other confounding variables, GSTT1 null genotype was also significantly associated with increased risk of gastric cancer (Random-effect OR = 1.43, 95%CI 1.20–1.71, P _OR <0.001, I² = 48.1%).

Conclusion

The meta-analysis provides strong evidence for the significant association between GSTT1 null genotype and increased risk of gastric cancer.     

Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial

Aims

To assess the determinants of exercise training-induced improvements in glucose control (HbA_1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.

Methods

A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).

Results

Changes in HbA_1C were associated with changes in adiponectin (r = −0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA_1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = −0.26; P<0.03), and PGC-1α (r = −0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA_1C.

Conclusions

Decreases in HbA_1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00458133","term_id":"NCT00458133"}}NCT00458133     

Leg Extension Power Is a Pre-Disaster Modifiable Risk Factor for Post-Traumatic Stress Disorder among Survivors of the Great East Japan Earthquake: A Retrospective Cohort Study

Background

Post-traumatic stress disorder (PTSD) is a common psychological problem following natural disasters. Although pre-disaster risk factors are important for early detection and proactive support, the examination of such has been limited to sociodemographic factors, which were largely unaffected by the disasters. We examined the association between pre-disaster physical functioning and lifestyle and PTSD symptoms five months after the earthquake in the Great East Japan Earthquake survivors who were participating in a pre-existing cohort study.

Methods

We designed a retrospective cohort study of a cooperative association in Sendai from August 2010 to August 2011. In 2010, lifestyle, physical condition, and sociodemographic factors were examined by self-reported questionnaires completed by 522 employees of this organization. We also measured the leg extension power of all the participants. PTSD symptoms were evaluated by the Japanese version of the Impact of Event Scale-Revised (IES-R-J) following the earthquake of 2011.

Results

In multivariate linear regression analysis, leg extension power (β = –0.128, P = 0.025), daily drinking (β  = 0.203, P = 0.006), and depressive symptoms (β  = 0.139, P = 0.008) were associated with total score of the IES-R-J among men. Moreover, for the IES-R-J subscale, leg extension power was also negatively associated with Intrusion (β = –0.114, P = 0.045) and Hyperarousal (β = –0.163, P = 0.004) after adjusting for all other significant variables. For women, hypertension (β  = 0.226, P = 0.032) and depressive symptoms (β  = 0.205, P = 0.046) were associated with the total score of the IES-R-J.

Conclusions

Leg extension power is a potentially modifiable pre-disaster risk factor among men for attenuating the severity of PTSD symptoms associated with great disasters such as the Great East Japan Earthquake among men.     

Association between Serum Chemerin Concentrations and Clinical Indices in Obesity or Metabolic Syndrome: A Meta-Analysis

Objective

Chemerin is a novel adipokine. Previous research has investigated the association between chemerin and clinical indices in patients with obesity or metabolic syndrome (MS), although the results obtained have been inconsistent. We conducted a meta-analysis to investigate the association between chemerin and clinical indicators of diabetes, MS and obesity with obesity or MS subjects.

Design and Methods

Studies were identified by searching the PubMed, the Cochrane Library, EMBASE and CNKI, databases beginning with the original report in July 2007 until the end of May 2013. For each variable, summary correlation coefficients were estimated using random-effects or fixed-effect meta-analysis with 95% confidence interval (CI) performed by STATA software.

Results

A total of eight studies with 20 clinical variables (total n = 1787) met the inclusion criteria. The meta-analyse of diabetes markers showed that FSI (r_s = 0.26; 95% CI = 0.21–0.31; P = 0.000), 2HPG (r_s = 0.06; 95% CI = 0.01–0.12; P = 0.030) and HOMA-IR (r_s = 0.178; 95% CI = 0.019–0.337; P = 0.028) were positively correlated with chemerin, however, FPG (r_s = 0.03, 95% CI = −0.02 to 0.08, P = 0.240) and HbA1c (r_s = −0.05; 95% CI = −0.24–0.15; P = 0.641) were not significantly correlated with chemerin. The meta-analyses of MS and obesity markers indicated that TG, TC, CRP BMI, TBF%, WC, WHR and Leptin were positively correlated with chemerin, nevertheless, SBP, DBP, LDL-C, HDL-C, ALT and r-GT were not significantly correlated, adiponectin was negatively correlated. Sensitivity analysis was performed and the summary results did not change significantly.

Conclusions

The results suggest that chemerin in patients with obesity or MS may be associated with obesity, imbalances in lipid and diabetes metabolism and insulin resistance. Chemerin played an important role in the pathophysiology of obesity and MS.     

The Efficacy and Safety of Selective H1-Antihistamine versus Leukotriene Receptor Antagonist for Seasonal Allergic Rhinitis: A Meta-Analysis

Background

Both selective H₁-antihistamine (SAH) and leukotriene receptor antagonist (LTRA) have been shown to be effective in treating patients with seasonal allergic rhinitis (SAR), but it is still uncertain which treatment option is optimal. This meta-analysis was aimed to compare the efficacy and safety of SAH and LTRA for SAR.

Materials and Methods

PubMed, EMBASE and the Cochrane Library were searched for all eligible studies that compared the efficacy and safety of SAH and LTRA for SAR up to September 7, 2014. The pooled mean difference (MD), odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed- or random-effects model.

Results

Nine studies with 5781 SAR patients were included. The results showed that SAH is superior to LTRA in terms of the daytime eye symptoms score (DESS) and composite symptoms score (CSS) for SAR (MD = 0.06, 95% CI, 0.03 to 0.10, P = 0.000, I ² = 99%; MD = 0.03, 95% CI, 0.01 to 0.05, P = 0.010, I ² = 98%), whereas LTRA overmatched SAH with respect to the night-time symptoms score (NSS) (MD = −0.04, 95% CI, −0.05 to −0.02, P = 0.000, I ² = 97%). Additionally, the results of subgroup analysis indicated that the dose, duration and gender of the patients might impact the comparisons of the effects of SAH and LTRA on their efficacy for SAR.

Conclusion

This meta-analysis suggested that SAH and LTRA have similar effects and safety for SAR, but SAH is more appropriate for daytime nasal symptoms (congestion, rhinorrhea, pruritus and sneezing), while LTRA is better suited for nighttime symptoms (difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening), respectively. Meanwhile, the dose, duration and gender of patients may influence the anti-SAR effects of SAH and LTRA.     

Complication Probability Models for Radiation-Induced Heart Valvular Dysfunction: Do Heart-Lung Interactions Play a Role?

Purpose

The purpose of this study is to compare different normal tissue complication probability (NTCP) models for predicting heart valve dysfunction (RVD) following thoracic irradiation.

Methods

All patients from our institutional Hodgkin lymphoma survivors database with analyzable datasets were included (n = 90). All patients were treated with three-dimensional conformal radiotherapy with a median total dose of 32 Gy. The cardiac toxicity profile was available for each patient. Heart and lung dose-volume histograms (DVHs) were extracted and both organs were considered for Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP model fitting using maximum likelihood estimation. Bootstrap refitting was used to test the robustness of the model fit. Model performance was estimated using the area under the receiver operating characteristic curve (AUC).

Results

Using only heart-DVHs, parameter estimates were, for the LKB model: D₅₀ = 32.8 Gy, n = 0.16 and m = 0.67; and for the RS model: D₅₀ = 32.4 Gy, s = 0.99 and γ = 0.42. AUC values were 0.67 for LKB and 0.66 for RS, respectively. Similar performance was obtained for models using only lung-DVHs (LKB: D₅₀ = 33.2 Gy, n = 0.01, m = 0.19, AUC = 0.68; RS: D₅₀ = 24.4 Gy, s = 0.99, γ = 2.12, AUC = 0.66). Bootstrap result showed that the parameter fits for lung-LKB were extremely robust. A combined heart-lung LKB model was also tested and showed a minor improvement (AUC = 0.70). However, the best performance was obtained using the previously determined multivariate regression model including maximum heart dose with increasing risk for larger heart and smaller lung volumes (AUC = 0.82).

Conclusions

The risk of radiation induced valvular disease cannot be modeled using NTCP models only based on heart dose-volume distribution. A predictive model with an improved performance can be obtained but requires the inclusion of heart and lung volume terms, indicating that heart-lung interactions are apparently important for this endpoint.     

Apolipoprotein C3 Polymorphisms,Cognitive Function and Diabetes in Caribbean Origin Hispanics

Background

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.

Methods

We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45–74) living in the Boston metropolitan area.

Results

Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.

Conclusions

In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.     

Association between Single Nucleotide Polymorphisms in the ADD3 Gene and Susceptibility to Biliary Atresia

Background and Objectives

Based on the results of previous studies, the ADD3 gene, located in the 10q24.2 region, may be a susceptibility gene of biliary atresia (BA). In this study, two single nucleotide polymorphisms (SNPs) in the ADD3 gene, rs17095355 C/T and rs10509906 G/C, were selected to investigate whether there is an association between these SNPs and susceptibility to BA in a Chinese population.

Methods

A total of 752 Han Chinese (134 BA cases and 618 ethnically matched healthy controls) were included in the present study. The ADD3 gene polymorphisms were genotyped using a TaqMan genotyping assay.

Results

Positive associations were found for the SNP rs17095355 in the codominant model; specifically, the frequencies of the CT and TT genotypes and the T allele were higher in the cases than the controls, demonstrating a significant risk for BA (odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.02–2.58; OR = 2.89, 95% CI = 1.72–4.86; and OR = 1.75, 95% CI = 1.34–2.29, respectively). Regarding rs10509906, the per-C-allele conferred an OR of 0.70 (95% CI = 0.49–1.00) under the additive model. A greater risk of BA was associated with the T_a-G_b (a for rs17095355 and b for rs10509906) haplotype (OR = 1.82, 95% CI = 1.27–2.61) compared with the C_a-C_b haplotype.

Conclusion

This study suggests that the ADD3 gene plays an important role in BA pathogenesis and reveals a significant association between two SNPs, rs17095355 and rs10509906, and BA.     

Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective

To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).

Methods

The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.

Results

Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, P_cor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, P_cor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, P_cor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, P_cor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, P_cor<0.05) were the cutoff values for screening ≥50% carotid stenosis.

Conclusions

Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.