A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.

Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.

Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait.

Subtype Specificity of Genetic Loci Associated With Stroke in 16 664 Cases and 32 792 Controls.

Background: Genome-wide association studies have identified multiple loci associated with stroke. However, the specific stroke subtypes affected, and whether loci influence both ischemic and hemorrhagic stroke, remains unknown. For loci associated with stroke, we aimed to infer the combination of stroke subtypes likely to be affected, and in doing so assess the extent to which such loci have homogeneous effects across stroke subtypes.

Continuous intestinal infusion of levodopa-carbidopa in patients with advanced Parkinson's disease in Spain: Subanalysis by autonomous community.

Objectives: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain.

Methods: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation.

Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke.

Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive.

Cross-sectional Comparison of the Epidemiology of DSM-5 Generalized Anxiety Disorder Across the Globe.

Importance: Generalized anxiety disorder (GAD) is poorly understood compared with other anxiety disorders, and debates persist about the seriousness of this disorder. Few data exist on GAD outside a small number of affluent, industrialized nations. No population-based data exist on GAD as it is currently defined in DSM-5.

Long-term effectiveness of levodopa-carbidopa intestinal gel in 177 Spanish patients with advanced Parkinson's disease.

Aim: To assess long-term effectiveness and tolerability of levodopa-carbidopa intestinal gel (LCIG) in Spanish patients with advanced Parkinson's disease.

Patients & Methods: This was an observational, multicenter, cross-sectional, retrospective study.

Results: Data of 177 patients were analyzed.

Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment.

Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression.

Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization.

Background: Collateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC.

Prenatal head growth and child neuropsychological development at age 14 months.

Objective: We sought to assess the association between prenatal head growth and child neuropsychological development in the general population.

Study Design: We evaluated 2104 children at the age of 14 months from a population-based birth cohort in Spain. Head circumference (HC) was measured by ultrasound examinations at weeks 12, 20, and 34 of gestation and by a nurse at birth.

Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.

The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing.

Effects of surgery and/or remifentanil administration on the expression of pERK1/2, c-Fos and dynorphin in the dorsal root ganglia in mice.

Tissue injury and/or opioids induce plastic changes in the spinal cord resulting in pain hypersensitivity; the contribution of the dorsal root ganglia (DRG) is poorly understood. We evaluated DRG phenotypic changes induced by surgery and/or remifentanil in a mice model of postoperative pain using as neuronal markers ERK1/2 and c-Fos; prodynorphin mRNA and dynorphin levels were also determined. We hypothesized that a correlation between nociception and DRG reactivity would occur.

B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen.

Neutrophils use immunoglobulins to clear antigen, but their role in immunoglobulin production is unknown. Here we identified neutrophils around the marginal zone (MZ) of the spleen, a B cell area specialized in T cell-independent immunoglobulin responses to circulating antigen. Neutrophils colonized peri-MZ areas after postnatal mucosal colonization by microbes and enhanced their B cell-helper function after receiving reprogramming signals, including interleukin 10 (IL-10), from splenic sinusoidal endothelial cells.

Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity.

Background: A strong rationale supports the role of antiangiogenic drugs in urothelial cancer. This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit.

Patients And Methods: This was a multicenter phase II trial with sunitinib 50 mg daily in 4/2-week schedule.

Staff regard towards working with substance users: a European multi-centre study.

Aims: To compare regard for working with different patient groups (including substance users) among different professional groups in different health-care settings in eight European countries.

Design: A multi-centre, cross-sectional comparative study.

Setting: Primary care, general psychiatry and specialist addiction services in Bulgaria, Greece, Italy, Poland, Scotland, Slovakia, Slovenia and Spain.

The association between intimate partner violence, alcohol and depression in family practice.

Background: Depressive symptoms, intimate partner violence and hazardous drinking are common among patients attending general practice. Despite the high prevalence of these three problems; the relationship between them remains relatively unexplored.

Methods: This paper explores the association between depressive symptoms, ever being afraid of a partner and hazardous drinking using cross-sectional screening data from 7667 randomly selected patients from a large primary care cohort study of 30 metropolitan and rural general practices in Victoria, Australia.

Redox balance and cellular inflammation in the diaphragm, limb muscles, and lungs of mechanically ventilated rats.

Background: High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury.

Methods: Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]).

Gas chromatography-mass spectrometry assay for the simultaneous quantification of drugs of abuse in human placenta at 12th week of gestation.

We describe the development and validation of a method for the quantification of drugs of abuse, using gas chromatography-mass spectrometry (GC/MS), in human placenta. Concentration ranges covered were 5-500 ng/g for amphetamine, methamphetamine, MDMA, methadone, cocaine, benzoylecgonine, cocaethylene, morphine, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, nicotine, and cotinine. Intra-assay and inter-assay imprecisions were less than 15.

In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations.

While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103).

Correcting serum concentrations of organochlorine compounds by lipids: alternatives to the organochlorine/total lipids ratio.

Introduction: When studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction.

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer.

Background: Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs).

Objective: To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC).

Methods: Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain.

Neurotoxic thioether adducts of 3,4-methylenedioxymethamphetamine identified in human urine after ecstasy ingestion.

3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely misused synthetic amphetamine derivative and a serotonergic neurotoxicant in animal models and possibly humans. The underlying mechanism of neurotoxicity involves the formation of reactive oxygen species although their source remains unclear. It has been postulated that MDMA-induced neurotoxicity is mediated via the formation of bioreactive metabolites.

Unsuspected exposure to cocaine in preschool children from a Mediterranean city detected by hair analysis.

We used hair testing to investigate the prevalence of unsuspected exposure to cocaine in a group of preschool children presenting to an urban pediatric emergency department without signs or symptoms suggestive of exposure. Hair samples were obtained from 90 children between 18 months and 5 years of age attending the emergency room of Hospital del Mar in Barcelona, Spain. In 85 cases, hair samples from the accompanying parent were also provided.

Stability of drugs of abuse in oral fluid collection devices with purpose of external quality assessment schemes.

As the stability of drugs of abuse in oral fluid can affect drug testing results, we evaluated this parameter together with recovery for the principal drugs of abuse in two collection devices typically used to ship oral fluid samples to testing laboratories. Two different samples were prepared using Cozart Drug Detection System and Intercept oral fluid collection devices with 600 ng/mL of 6-monoacetylmorphine (6-MAM) and cocaine and 240 ng/mL of Delta-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta-tetrahydrocannabinol (THCCOOH). Samples were sent at ambient temperature by courier to the participating laboratories (n = 19) the same day of preparation.