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Prolactin receptor (PRLR) gene plays a crucial role in the milk production, reproduction and the growth of mammals. To fully characterize the structure of the mutation and to further study the function of the goat PRLR gene, two insertion/deletion (indel) loci (12 bp; 16-bp; 5-bp) were detected in 1038 Shaanbei white cashmere (SBWC) goats. Associated analysis revealed that the 16-bp indel mutation was significantly associated the body length, body height, chest depth (CD), body length index (BLI), heart girth index and cannon circumference index (CCI) (p < 0.05). The polymorphism of 5-bp indel was significantly associated with CD, heart girth, CCI and BLI (p < 0.05). Overall, individuals with genotype DD showed better phenotypic traits than individuals with other genotypes at the two loci of PRLR gene in SBWC goat. These findings suggested that the two novel indels within the caprine PRLR gene could be considered as effective DNA molecular markers and could provide a valuable theoretical basis for the application of marker-assisted selection in the goat industry. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have indicated an association between coffee consumption and amyotrophic lateral sclerosis (ALS). Nevertheless, whether the association is causal is still unclear. We conducted a Mendelian randomization study to explore whether coffee consumption is causally related to ALS. Methods: Two genome-wide association studies (GWASs) investigating coffee consumption (n = 129,422 and 375,833, respectively) were adopted to define instrumental variables for coffee consumption (high vs. infrequent/no, 1 cup/day increase, and 50% increase). Summary-level data for ALS were adopted from a large GWAS of ALS with a total of 20,806 cases and 59,804 controls. Results: Genetically predicted higher coffee consumption was not associated with ALS. The ORs were 1.02 (95% CI: 0.93–1.13; p = 0.649) for high vs. infrequent/no, 0.98 (95% CI: 0.84–1.15; p = 0.822) for 1 cup/day increase, 0.97 (95% CI: 0.79–1.19; p = 0.766) for 50% increase. Sensitivity analyses yielded consistent results. No pleiotropic bias and heterogeneity were observed. Conclusion: Using multiple approaches and sensitivity analyses, our MR results show that genetically predicted coffee consumption was not associated with ALS. Further studies are warranted to explore the effect of coffee consumption on ALS progression. [ABSTRACT FROM AUTHOR]

It is always very difficult to efficiently and accurately solve a system of differential equations coupled with moving free boundaries, while such a system has been widely applied to describe many physical/biological phenomena such as the dynamics of spreading population. The main purpose of this paper is to introduce efficient numerical methods within a general framework for solving such systems with moving free boundaries. The major numerical challenge is to track the moving free boundaries, especially for high spatial dimensions. To overcome this, a front tracking framework coupled with implicit solver is first introduced for the 2D model with radial symmetry. For the general 2D model, a level set approach is employed to more efficiently treat complicated topological changes. The accuracy and order of convergence for the proposed methods are discussed, and the numerical simulations agree well with theoretical results. [ABSTRACT FROM AUTHOR]

Runt-related transcription factor 2 (Runx2) is characterized by its critical functions in osteoblastic and ovulatory processes. The goal of this study was to explore the insertion/deletion (indel) variants of this gene and to evaluate their association with productive traits. Herein, a 12 bp and 6 bp insertion within the Runx2 gene was uncovered in Shaanbei white cashmere goats (SBWC; n = 1200). Chi-square analysis revealed that the 12 bp insertion was related to litter size (p < 0.01). Further association analysis also found this insertion was significantly associated with litter size (p = 1.1E-5). Interestingly, this insertion was also significantly associated with chest circumference (p = 0.018). Additionally, the 6 bp insertion was associated with body length (p = 0.003), chest width (p = 0.011), and chest circumference (p = 0.005). Furthermore, diplotype associations also uncovered that the combined genotypes of these two indels also significantly affected litter size and growth traits (p < 0.05). These findings suggested that these two insertions within the Runx2 gene were significantly associated with reproduction and growth traits, which would make them beneficial functional DNA markers that can be used in goat breeding. [ABSTRACT FROM AUTHOR]

Background: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. Methods: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. Results: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. Conclusion: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest an association between dietary fiber intake and risk of Barrett's esophagus and esophageal cancer. However, the results are inconsistent.Objective: To conduct a meta-analysis of observational studies to assess this association.Design: All eligible studies were identified by electronic searches in PubMed and Embase through February 2015. Dose-response, subgroup, sensitivity, and publication bias analyses were performed.Results: A total of 15 studies involving 16,885 subjects were included in the meta-analysis. The pooled odds ratio for the highest compared with the lowest dietary fiber intake was 0.52 (95% CI, 0.43-0.64). Stratified analyses for tumor subtype, study design, geographic location, fiber type, publication year, total sample size, and quality score yielded consistent results. Dose-response analysis indicated that a 10-g/d increment in dietary fiber intake was associated with a 31% reduction in Barrett's esophagus and esophageal cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the overall risk estimate.Conclusions: Our findings indicate that dietary fiber intake is inversely associated with risk of Barrett's esophagus and esophageal cancer. Further large prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Aims: Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke.Methods: We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission.Results: None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders.Post hocanalysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33–5.10) and deep CMBs (OR 2.10, 95%CI 1.08–3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant.Conclusion: In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END. [ABSTRACT FROM PUBLISHER]

Background: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months.Methods: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0–1) or good (grades 2–4).Results: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29–8.19;p= 0.012) and long ORT (OR 3.97, 95% CI: 1.66–9.54;p= 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39–21.61;p< 0.001) was independently associated with unfavorable outcome at 3 months.Conclusion: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT. [ABSTRACT FROM AUTHOR]

Background: In 2009, a genome-wide association study (GWAS) identified two variants (rs12425791 and rs11833579) nearNINJ2gene that confer susceptibility to stroke in Caucasian populations. Recently, a number of studies have been conducted to replicate this finding in Asian populations. However, the results are conflicting. Thus, we performed a quantitative analysis to summarize the evidence regarding the association between these two polymorphisms and ischemic stroke risk.Methods: Pertinent studies were identified by searching PubMed and Embase through September 2014. Studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between these two polymorphisms and stroke risk were included.Results: Eight independent publications, with 8626 cases and 8046 controls for rs12425791 and 9142 cases and 8657 controls for rs11833579, were included. Overall, significantly increased ischemic stroke risk was associated with rs12425791 A allele when all studies were pooled into the meta-analysis (AA/GA vs. GG: OR = 1.08, 95% CI: 1.01–1.14). However, rs11833579 was not associated with increased stroke risk in any genetic model.Conclusions: These findings indicate that rs12425791 G>A polymorphism may be a low-penetrance susceptibility marker of stroke in Asian populations and further studies are warranted to verify this association. [ABSTRACT FROM AUTHOR]

Background:Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design.Methods:The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models.Results:The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p< 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34+CD133+CD309+cells:r= 0.510,p= 0.001; CD34+CD133−CD309+cells:r= 0.262,p= 0.004; CD34−CD133+CD309+cells:r= 0.348,p< 0.001).Conclusions:Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke. [ABSTRACT FROM PUBLISHER]

Polymorphisms ofCYP2C19have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts ofCYP2C19polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010.CYP2C19variants (*2, *3, and*17) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9–18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies ofCYP2C19*1, *2, *3, and*17alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort.CYP2C19loss-of-function allele (*2and*3, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31–3.56,p = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent,CYP2C19LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39–3.84,p = 0.001). No significant association betweenCYP2C19gain-of-function (*17, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers ofCYP2C19LOF allele may have increased risk of recurrence. [ABSTRACT FROM PUBLISHER]

Nerve growth factor (NGF) has been proved with the potential of promoting neurogenesis in adult mammalians. This study was aimed to investigate the effect of intranasal (IN) NGF on striatal neurogenesis and functional recovery in adult rats with focal cerebral ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h, and then reperfused. NGF or vehicle was intranasally administered 24 h after cerebral reperfusion, and the treatments continued for 6 consecutive days there after. All animals were injected with 5-bromodeoxyuridine (BrdU) twice daily for 5--7 days after MCAO, and sacrificed 1 day and 28 days, respectively, after the last BrdU injection. Neural cell proliferation and survival in different brain regions were analyzed. Functional tests and immunohistochemical staining were also performed. The results showed that treatment with IN NGF failed to increase cell proliferation but improved survival of newly generated cells in ipsilateral striatum and subventricular zones (SVZ). Double immunofluorescence with BrdU and neuronal nuclei protein, a mature neuronal marker, were increased in striatum and SVZ in rats treated with IN NGF. The functional recovery was also observed at time of neurogenesis enhancement in striate. In conclusion, IN NGF may enhance neurogenesis and survival of newly generated cells, which may result in improved functional recovery after cerebral ischemia. [ABSTRACT FROM AUTHOR]