A minimum of 32 individual adult worms were genotyped at position

A minimum of 32 individual adult worms were genotyped at position 24 of the rDNA ITS-2 for each ATM/ATR phosphorylation population to determine species identity (296 worms in total). One population from Georgia was identified as 100% H. conforms with the remaining nine populations identified as 100% H. placei. For the H. contortus population,

29 out of 32 worms carried the P200Y (TAC) isotype-1 beta-tubulin and 2 out of 32 worms carried the P167Y (TAC) benzimidazole resistance associated polymorphisms respectively. For H. placei, six out of the nine populations contained the P200Y(TAC) isotype-1 beta-tubulin benzimidazole resistance associated polymorphism at low frequency (between 1.6% and 9.4%) with no resistance associated polymorphisms being identified at the P198 and P167 codons. This is the first report of the P200Y (TAC) isotype-1 beta-tubulin benzimidazole resistance associated polymorphism in H. placei. The presence of this mutation in multiple independent H. placei populations indicates the risk of resistance emerging in this parasite should benzimidazoles be

intensively used for parasite control in US cattle. (C) 2014 Elsevier B.V. All rights reserved.”
“Objective: To investigate the beta 2-adrenoceptor (beta 2AR)-beta-arrestin2-nuclear factor-kappa B (NF-kappa B) signal transduction pathway and the intervention effects of oxymatrine in a rat model of ulcerative colitis. Methods: Forty SD rats were

randomly divided into four groups, Ferroptosis inhibitor review which included the normal control group, the model group, the mesalazine group and the oxymatrine treatment group, with 10 rats per group. Experimental colitis induced with trinitrobenzene sulfonic acid (TNBS) was established in each group except the normal control group. The rats in the oxymatrine treatment group were treated with intramuscular injection of oxymatrine 63 mg/(kg.d) for 15 days and the rats in the mesalazine group were treated with mesalazine solution 0.5 g/(kg.d) by gastric lavage for 15 days. The rats in the normal Daporinad control group and model group were treated with 3 mL water by gastric lavage for 15 days. Diarrhea and bloody stool were carefully observed. Histological changes in colonic tissue were examined on day 7 in 2 rats per group that were randomly selected. The expression of beta 2AR, beta-arrestin2 and NF-kappa Bp65 in colon tissue and spleen lymphocytes were detected with immunohistochemistry and Western immunoblotting techniques on day 16 after fasting for 24 h. Six rats died of lavage with 2 each in the normal control, the model group and the mesalazine group; and were not included in the analysis.

Genes

related to energy metabolism were mostly downregula

Genes

related to energy metabolism were mostly downregulated in diabetic skeletal muscle and visceral adipose tissue, while they were upregulated in the diabetic liver. This observed dysregulation in energy-related metabolism may be the underlying factor leading to the molecular mechanisms responsible for the insulin resistance of patients with T2D.”
“Nanoparticles have successfully been employed in immunometric assays that require high sensitivity. Certain analytes, however, require dynamic ranges (DRs) around a predetermined cut-off value. Here, we have studied the effects that antibody orientation and addition of free solid-phase and detection antibodies have on assay sensitivity and DR in traditional sandwich-type immunoassays. D-dimer and cardiac troponin I (cTnI), both routinely used in critical care testing, were applied as model analytes. The assays were performed

in microtitration wells with preimmobilized buy SNX-5422 solid-phase antibody. Inherently LY3039478 in vitro fluorescent nanoparticles coated with second antibody were used to detect the analyte. The selection of antibody orientation and addition of free solid-phase or detection antibody, with nanoparticles and calibrator, desensitized the assays and extended the DR. With D-dimer the upper limit of the DR was improved from 50 to 10,000 ng/ml, and with cTnI from 25 to 1000 ng/ml. Regression analysis with the Stago STA Liatest D-dimer assay yielded a slope (95% confidence interval) of 0.09 (0.07-0.11) and a yintercept of 7.79 (-17.87-2.29) ng/L (n = 65, 4EGI-1 inhibitor r = 0.906). Thus it is concluded that Europium(III)-chelate-doped nanoparticles can also be employed in immunoassays that require wide DRs around a certain cut-off limit. (C) 2013 Elsevier Inc. All rights reserved.”
“Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview

on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment.”
“A field study was conducted to compare the effect of toltrazuril and diclazuril treatment against Eimeria infection in 142 naturally infected, weaned lambs aged 45-60 days.

Microstructural

Microstructural ATM/ATR tumor and morphological studies of these films were carried out by field emission scanning electron microscopy and atomic force microscopy techniques. Infrared emittance

(epsilon(ir)) of the films was measured by a Fourier transform infrared spectrophotometer. Nanoindentation technique was employed to evaluate nanohardness and Young’s modulus of the films. The optimized bi-layer SiO2-Al2O3 film showed up to 850% increase in sir as compared to those of the bare substrates. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.”
“Cognitive dysfunction, as a consequence of dementia, is a significant cause of morbidity lacking efficacious treatment. Females comprise at least half of this demographic but have been vastly underrepresented in preclinical studies. The current study addressed this gap by assessing the protective efficacy of physical exercise and cognitive activity on learning and memory outcomes in a rat model of vascular dementia. Forty ovariectomized Sprague-Dawley rats (similar to 6 months old) were exposed to either a diet high in saturated fats and refined sugars or standard laboratory chow and underwent either chronic bilateral carotid

occlusion or Sham surgery. Learning and memory abilities were evaluated using standard cognitive outcomes over the ensuing 6 months, SNS-032 followed by histologic analyses of hippocampal CA1 neurons. In Experiment 1, we confirmed hypoperfusion-induced cognitive dysfunction using a 2 x 2 (Surgery x Diet) experimental design,

without alterations in hippocampal architecture. In Experiment 2, hypoperfused animals were either exposed to alternating days of physical (wheel running) and cognitive activity (modified Hebb-Williams maze) or sedentary housing. In contrast to males, this combination rehabilitation paradigm did not improve cognition or histopathologic outcomes in hypoperfused animals. These findings, highlighting differences between female and male animals, show the necessity of including both sexes in preclinical experimentation.”
“Inflammation is associated with enhanced vascular permeability, production of inflammatory markers and over production of reactive oxygen species (ROS) with depletion selleck inhibitor of endogenous antioxidants. Several drug targeting approaches to inflammation taking clues from these events have been evolved. Surprisingly, a drug targeting approach utilizing abundant oxidative stress at inflammatory site has not been followed. Antioxidant surface loaded liposomes might preferentially localize at inflammatory sites via redox interaction where at high level of ROS exist. The present study was focused to investigate the role of antioxidant as a targeting ligand on the surface of liposome employing rat granuloma air pouch model of inflammation. We developed conventional and antioxidant loaded diclofenac (DFS) liposomes (co-enzyme Q10 and ascorbyl palmitate) for i.v.

Results: Fifteen patients with intracerebral hemorrhage received

Results: Fifteen patients with intracerebral hemorrhage received 40-90 mu g/kg of rFVIIa and underwent surgical hematoma evacuation at a median time of five hours following symptom onset. Median pre-operative clot volume was 60 ml. decreasing to 2 ml post-operatively. There were no thromboembolic adverse events. Thirteen patients survived, 11 (73%) were independent, and two (13%)

had a moderate to severe disability. These outcomes were significantly better than expected based on the median ICH score (40% mortality) and based on median ICH Grading Scale (18% good outcome). Conclusions: The pre or peri-operative administration of rFVIIa resulted in minimal 5-Fluoracil solubility dmso residual or recurrent hematoma volume and may be an important adjunct to surgery in patients with intracerebral hemorrhage.”
“We report a robust method for synthesis of monodisperse. PbSeTe single ternary alloy and core/shell heterostructured nanocubes, respectively. The key synthetic strategy to produce such different

Adriamycin classes of nanocubes is to precisely control the time of reaction and successive growth. The crystallinity, shape/size distributions, structural characteristics, and compositions of as-prepared nanocubes, both, ternary alloy and core/shell, were carefully studied: A plausible growth mechanism for developing, each type of lead chalcogenide nanocubes is proposed. These delicately designed PbSeTe nanoscale architectures offer tunable compositions in PbSeTe ternary alloy and nano-interfaces in Panobinostat purchase core/shell nanocubes, which are the critical factors in controlling thermal conductivity for applications in thermoelectrics.”
“In the present study, we used Caenorhabditis elegans assay system to investigate in vivo toxicity from clentuberol and ractopamine and the possible underlying mechanism. Both acute and prolonged exposures to clentuberol or ractopamine

decreased brood size and locomotion behavior, and induced intestinal autofluorescence and reactive oxygen species (ROS) production. Although acute exposure to the examined concentrations of clentuberol or ractopamine did not induce lethality, prolonged exposure to 10 mu g/L of clentuberol and ractopamine reduced lifespan. At relatively high concentrations, ractopamine exhibited more severe toxicity than clentuberol on nematodes. Overexpression of sod-2 gene encoding a Mn-SOD to prevent induction of oxidative stress effectively inhibited toxicity from clentuberol or ractopamine. Besides oxidative stress, we found that clentuberol might reduce lifespan through influencing insulin/IGF signaling pathway; however, ractopamine might reduce lifespan through affecting both insulin/IGF signaling pathway and TOR signaling pathway. Ractopamine more severely decreased expression levels of daf-16, sgk-1, skn-1, and aak-2 genes than clentuberol, and increased expression levels of daf-2 and age-1 genes at the examined concentration. Therefore, the C.

33) Food insecurity was associated with a trend towards greater

33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. Conclusion: Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study. (C) 2014 S. Karger AG, Basel”
“BACKGROUNDThe aim of this study was to evaluate a preparation of vegetable paste with bovine blood in order to maximize the protein content using linear programming, and Quisinostat inhibitor to analyze the product characteristics

and quality of bovine blood-enriched vegetable paste dried in a spouted bed. The drying experiments were performed by evaluating the effects of inlet air temperature, paste flow rate and paste solids concentration on the dried product characteristics and quality (functional and nutritional properties). RESULTSThe vegetable paste enriched with bovine blood was a good source of protein (approximate to 0.20gg(-1), dry basis), and the linear programming was adequate to select the constituents (carrot,

onion, potato, kale, tomato, soybean oil and bovine blood) and optimize their quantities. The drying conditions of bovine blood-enriched vegetable paste in the spouted bed that gave the best product characteristics were an air temperature of 110 degrees C and a paste flow rate of 600 mL h(-1) with 0.07gg(-1) solids concentration. CONCLUSIONThe addition of bovine blood to vegetable paste by linear Androgen Receptor inhibitor programming increased the protein content of the paste and improved its functional properties and digestibility. The powder obtained from the spouted bed drier showed suitable functional and nutritional properties and was also a good source of antioxidant compounds. (c) 2014 Society of Chemical Industry”
“We present a safety and efficacy data analysis Epigenetic animal study of cabazitaxel treatment in 49 patients with metastatic castrate-resistant prostate cancer (mCRPC) who participated in the Dutch Compassionate Use Program (CUP). Median

time to prostate-specific antigen (PSA) progression was 2.8 months, median overall survival (OS) was 8.7 months. Toxicities were acceptable, the most frequent serious adverse events (SAEs) being hematuria (8.2%) and urosepsis (6.1%).\n\nBackground: Cabazitaxel has been reimbursed as a second-line therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC) in the Netherlands since 2011. Before reimbursement was available, cabazitaxel was provided through a Compassionate Use Program (CUP). We report the results of the Dutch CUP, detailing the safety and efficacy of cabazitaxel in a routine clinical practice setting. Patients and Methods: Safety and efficacy data of all 5 Dutch centers participating in the cabazitaxel CUP were collected. Safety data were collected prospectively using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0.

001, P = 0 005) High expression levels of cytoplasmic c-Src was

001, P = 0.005). High expression levels of cytoplasmic c-Src was associated with worse disease-specific survival (P = 0.026) after completing 5 years of tamoxifen therapy. However, high expression of c-Src at any cellular location did not show any association with de novo relapse on tamoxifen (c-Src nuc P = 0.906, c-Src cyto P = 0.735 and c-Src memb P = 0.791).\n\nConclusions No translational evidence was found in this study

to support a role for Src kinase in developing de novo tamoxifen resistance. However, based on our findings on late clinical outcome, patients with high cytoplasmic c-Src may be selected for continuing endocrine therapy to prevent worsening prognosis.”
“This study was carried out to evaluate the clinical significance of ascitic fluid carcinoembryonic antigen (CEA) in IPI-145 Angiogenesis inhibitor advanced gastric cancer patients

with ascites.\n\nFrom November 2001 to February 2008, 119 gastric cancer patients CA4P chemical structure with concurrent ascites who were clinically diagnosed with carcinomatosis, were retrospectively reviewed with regard to ascitic fluid cytology and clinicopathological parameters. Serum CEA (sCEA) and ascitic fluid CEA (aCEA) were measured using a chemiluminescent enzyme immunoassay.\n\nThe patients’ median age was 50 years (range 23-80 years). The median value of aCEA was significantly higher than sCEA [130.5 ng/ml (range 0.2-12.211 ng/ml) vs. 2.1 ng/ml (range 0.02-8.152 ng/ml), p < 0.001]. Sixty-five patients (54.6%) had positive ascitic fluid cytology. The median overall survival

of all patients was 3.0 months (95% CI 2.0-4.0 months). The patients with low aCEA (< 5 ng/ml) had a significantly longer overall survival compared to patients with high aCEA (a parts per thousand yen5 ng/ml) (7.4 months vs. 2.3 months, p = 0.003). However, we found no difference in overall survival according to ascitic fluid cytology (median, 3.0 months vs. 2.5 months, p = 0.530). Multivariate analysis also demonstrated that aCEA levels of more than 5 ng/ml were associated with poor prognosis (HR = 2.88; 95% CI 1.45-5.74; p = 0.003), while sCEA levels were not Selleck Autophagy Compound Library associated with poor prognosis (HR = 1.15; 95% CI 0.67-2.03; p = 0.622).\n\nThese results suggest that aCEA levels can be used as a prognostic marker for advanced gastric cancer patients with ascites.”
“Chemical exchange saturation transfer (CEST) imaging has been used experimentally in a large range of applications. However, full quantification of CEST effects in?vivo using standard imaging sequences is time consuming as a large number of saturation frequency offsets, each followed by an imaging readout, are required to define a z spectrum. Furthermore, outside the brain, the presence of fat can confound the interpretation of z spectra.

These results may be related to an up-regulation of GRP78 express

These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.”
“The effects of salicylic acid (SA) on the rate of respiration and the activity of cyanide-resistant sensitive to salicylhydroxamic acid oxidation pathway in detached etiolated cotyledons of yellow lupine (Lupinus luteus buy LCL161 L.) and mitochondria isolated from these cotyledons were studied. Cotyledon treatment with 1 mM SA for 12

h increased the rate of oxygen uptake predominantly due to the activation of cyanide-resistant respiration (CRR) and alternative pathway of mitochondrial oxidation. It was established that the lupine genome encodes at least two isoforms of alternative Buparlisib cost oxidase (AO), LuAOX1 and LuAOX2, with the mol wt of about 35 kD. These proteins are always present in the mitochondria of etiolated lupine cotyledons, but their level increased rapidly after cotyledon treatment with SA, probably by increasing the mRNA content of the corresponding genes. SA-induced expression of Aox genes was correlated with the activation of CRR and an increase in the maximal activity (capacity) of AO in both detached yellow lupine cotyledons and mitochondria isolated

from them.”
“In 2008, in total there were 202 158 abortions performed in England and Wales and 13 817 in Scotland, unfortunately one of the most common gynaecological procedures. ‘Care closer to home’ applied to this service, as part of a holistic integrated care pathway, can improve access and choice and reduce cost whilst continuing to focus on clinical quality and safety and

work towards reducing the number of primary and repeat abortions. Whilst constraints remain within Law, there are ways to change services to help reduce barriers to access not just to abortion but also the essential allied interventions of contraception, sexual health and counselling and support. The first will be reflected in the number of women able to have their abortions earlier, therefore more safely and at lesser cost. It would build on service changes to date, which has allowed women more choice of the method of abortion. selleck chemical The integration of contraceptive services should impact positively on the currently high level of repeat abortions. Bringing care closer to home, into the communities within which women spend their lives, is an important strategy in addressing the quality agenda in abortion care. (c) 2010 Elsevier Ltd. All rights reserved.”
“Microorganisms and the processes they mediate serve as the metabolic foundation of cold seeps. We characterized a suite of biogeochemical constituents and quantified rates of two key microbial processes, Sulfate Reduction (SR) and Anaerobic Oxidation of Methane (AOM), to assess variability between habitats at water depths exceeding 1000 m in the northern Gulf of Mexico.


“Background: Bcl-2 promotes cell survival by inhibiting ad


“Background: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.\n\nMethods: Here, we quantitatively assessed Bcl-2 expression in two large and

independent cohorts to investigate the impact of Bcl-2 on survival. AQUA (R), a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients.

An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome.\n\nResults: Fifty % and 52% of the cases were classified selleck products as high Aurora Kinase inhibitor expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p

= 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005).\n\nConclusions: Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.”
“In Asia, questions regarding the burden of Haemophilus influenzae type b (Hib) disease have delayed decision-making on introduction of Hib vaccine. However, over the past decade many studies have been published regarding Hib disease burden BVD-523 mw in Asia. We conducted a systematic literature review of all reports of Hib disease burden in Asia between 1998 and 2009, and critically reviewed their methods and data quality. We identified 94 studies from 28 countries in Asia presenting data on Hib disease burden. Of the 94 studies reviewed, 49 (52%) used a case definition consistent with World Health Organization standards, and 47 (50%) described laboratory methodology used. Twenty-seven surveillance studies presented data on incidence of Hib disease, with 8 (30%) accounting for missed cases, 6 (15%) accounting for cases with missed diagnostic tests, and 2 (7%) that considered prior antibiotic use.

Combining all 5 beneficial substitutions resulted in the mutant H

Combining all 5 beneficial substitutions resulted in the mutant HF5 with a 4.7-fold increase in half-life, with thermal inactivation at 93 degrees C, and complete lack of substrate inhibition toward the substrate p-nitrophenyl-beta-D-glucopyranoside at lower reaction temperatures. The results of this study provide valuable information on amino acid substitutions related to thermostability and substrate Proteasome inhibitor inhibition of BglY. (C) 2012 Elsevier Ltd. All rights reserved.”
“Patients with cyanotic congenital cardiac disease often develop major aortopulmonary collaterals Vascular endothelial growth factor is a key promoter of angiogenesis. Its soluble receptor-1

acts as a potent antagonist We studied 30 infants with cyanotic congenital cardiac disease find more and 27 infants with acyanotic congenital cardiac disease. Central venous plasma vascular endothelial growth factor and soluble vascular endothelial growth factor receptor-1 levels were measured before, and 24 and 96 hours after surgery There was no difference between plasma vascular endothelial growth factor levels in infants with cyanotic and those with acyanotic congenital cardiac disease In cyanotic infants, the soluble vascular endothelial growth factor receptor-1 levels tended to be higher than in the acyanotic infants. In conclusion, there is no significant difference in the plasma

levels of vascular endothelial growth factor and its soluble receptor-1. between infants with cyanotic and those with acyanotic congenital cardiac disease”
“Daytime Advanced Spaceborne Thermal Emission and reflection Radiometer (ASTER) data and the consequent nighttime Moderate Resolution Imaging Spectroradiometer (MODIS) data have been utilized to

retrieve the sea surface temperature (SST) and apparent thermal inertia (ATI). They were used to detect the signature of natural oil seepage in Yingge Sea Basin (YSB) buy Dinaciclib and South Yellow Sea (SYS). In this paper, ATI was used for the first time to detect the signature of natural oil seepage. ATI is an approximation of the real thermal inertia and can be expressed as a function of surface albedo and temperature difference between day and night. Surface albedo can be calculated by weighting spectral reflectivities in visible and near-infrared bands from ASTER data. The spectral reflectivities can be obtained after performing atmospheric correction using the 6S model. An iterative self-consistent split-window algorithm was employed to retrieve the daytime SSTs from ASTER data and nighttime SSTs from MODIS data. Because of the spatial resolution difference between ASTER and MODIS data, the nighttime SST derived from MODIS data was downscaled from 1km to 90m using the pixel block intensity modulation (PBIM) method. Two study areas, YSB and SYS, were selected to detect the possible signature of the natural oil seepage.

Immunohistochemical analysis of four of the differentially expres

Immunohistochemical analysis of four of the differentially expressed proteins in the endometrium showed concordant results. Functional assay showed that blastocyst attachment was statistically significantly reduced upon inhibition of aminopeptidase N. Conclusion(s): The luminal cell surface proteome of the prereceptive and receptive endometria differs, and aminopeptidase N is potentially involved in embryo attachment. (Fertil Steril (R) 2015; 103: 853-61. (C) 2015 by American Society for Reproductive Medicine.)”
“Ulcerative colitis is an idiopathic, chronic

and relapsing inflammatory bowel disease, which elicits the risk of colorectal cancer, the third most common malignancy in humans. It has been known for a long time that oxidative stress is a major buy DMH1 pathogenic factor in the inflamed tissue that can pave the way towards DNA damage and carcinogenesis. However, the DNA damage produced HSP990 price due to oxidative stress in the inflamed tissue is not limited to the local site but extends globally, thereby augmenting the risk of global carcinogenesis. Targeting oxidative stress may provide an exciting avenue to combat

inflammation-associated local as well as global DNA damage and the subsequent carcinogenesis. The present review portrays the role of oxidative stress in the pathogenesis of ulcerative colitis and the associated local as well as global DNA damage, which may lead to carcinogenesis.”
“Objective: The aim of this study was to identify the candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms that contribute to schizophrenia susceptibility and to generate a SNP to gene to pathway hypothesis using an analytical pathway-based approach.\n\nMethods: We used schizophrenia GWAS data of the genotypes of 660,259 SNPs in 1378 controls and 1351 cases of European descent after quality control filtering. ICSNPathway (Identify learn more candidate Causal SNPs

and Pathways) analysis was applied to the schizophrenia GWAS dataset The first stage involved the pre-selection of candidate SNPs by linkage disequilibrium analysis and the functional SNP annotation of the most significant SNPs found. The second stage involved the annotation of biological mechanisms for the pre-selected candidate SNPs using improved-gene set enrichment analysis.\n\nResults: ICSNPathway analysis identified fifteen candidate SNPs, ten candidate pathways, and nine hypothetical biological mechanisms. The most strongly associated potential pathways were as follows. First, rs1644731 and rs1644730 to RDH8 to estrogen biosynthetic process (p < 0.001, FDR < 0.001). The genes involved in this pathway are RDH8 and HSD3B1 (p < 0.05). All-trans-retinol dehydrogenase (RDH8) is a visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol in the presence of NADPH.