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Simple Summary: Hepsin is a serine protease whose deregulation leads to tumor invasion and metastasis in many tumor types. In colorectal cancer, the role of hepsin is unknown, so we aimed to study the correlations between its expression and clinical-histopathological variables of patients with this cancer. We recruited 169 patients with localized disease and 118 with metastatic cancer at diagnosis, and then, we measured hepsin staining from primary biopsy in order to correlate it with time-to-event variables, laboratory data, genetic alterations, histologic features, etc. Our results demonstrated hepsin was an independent prognosis factor for metastasis and thrombosis in patients with localized disease, whereas among metastatic subjects, lower levels of hepsin were associated with highest tumor dedifferentiation and spread to distant organs. These results point to hepsin as a potential biomarker for considerable complications in patients with colorectal cancer. In addition, this article brings to light new information about the implication of hepsin in colorectal cancer. Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal–Wallis tests, Kaplan–Meier and Aalen–Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes. [ABSTRACT FROM AUTHOR]

Telomere length has been associated with the development of cancer. Studies have shown that shorter telomere length may be related to a decreased risk of cutaneous melanoma. Furthermore, deregulation of the telomere-maintaining gene complexes , has been related to this oncogenic process. Some variants in these genes seem to be correlated with a change in telomerase expression. We examined the effect of 10 single nucleotide polymorphisms (SNPs) in the TERT gene (encoding telomerase), one SNP in the related TERT-CLPTM1L locus and one SNP in the TRF1 gene with telomere length, and its influence on melanoma risk in 970 Spanish cases and 733 Spanish controls. Genotypes were determined using KASP technology, and telomere length was measured by quantitative polymerase chain reaction (PCR) on DNA extracted from peripheral blood leucocytes. Our results demonstrate that shorter telomere length is associated with a decreased risk of melanoma in our population (global p -value, 2.69 × 10 −11 ), which may be caused by a diminution of proliferative potential of nevi (melanoma precursor cells). We also obtained significant results when we tested the association between rs401681 variant ( TERT-CLPTM1L locus ) with melanoma risk (Odds ratio, OR; 95% confidence interval, CI = 1.24 (1.08–1.43); p -value, 3 × 10 −3 ). This is the largest telomere-related study undertaken in a Spanish population to date. Furthermore, this study represents a comprehensive analysis of some of the most relevant telomere pathway genes in relation to cutaneous melanoma susceptibility. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the presence of periodontal disease among patients with rheumatoid arthritis (RA) in comparison with a control group. Method and Materials: The study included 44 patients diagnosed with RA according to American Rheumatism Association (ARA) criteria, who were attending the Morales Meseguer Hospital Rheumatology Service (Murcia, Spain), and 41 control subjects. Patients younger than 18 years or patients suffering systemic diseases that could affect the immune system were excluded. Age, sex, smoking habits, alcohol consumption, and body mass index were registered. Each patient underwent a full periodontal examination. Results: Bleeding on probing was significantly greater in the RA group (0.9±0.36) than the control (P < .001). The Plaque Index was significantly higher in the RA group (0.76±0.34) versus the control group (0.55±0.2) (P<.001). RA patients showed a 0.13 increased risk of periodontal disease (95% confidence interval, 0.05-0.37). Conclusion: Patients with RA suffered a higher risk of periodontal disease and for this reason these patients must be instructed to intensify their oral hygiene regimes. [ABSTRACT FROM AUTHOR]

Antenatal exposure to organic pollutants is a leading public health problem. Meconium is a unique matrix to perform prenatal studies because it enables us to retrospectively evaluate fetal exposure accumulated during the second and third trimester. The aim of the present study was to evaluate associations between organic pollutant levels in meconium and birth weight in NW Spain. In this study, we quantify the concentrations of 50 organic pollutants together with the total values of the most important chemical groups in meconium using gas chromatography coupled to tandem mass spectrometry. Organochlorine pesticides, polychlorinated biphenyls and polybrominated diphenyl ethers were detected with the highest levels in meconium from small for gestational age newborns. It was estimated that several congeners were statistically significant (p<0.05). However, organophosphorus pesticides attained higher concentrations in newborns with an appropriate weight. The occurrence of transplacental transfer can be confirmed. Prenatal exposure to organic pollutants was associated with a decrease in birth weight and, therefore, organic pollutants could have an impact on fetal growth. Nevertheless, these results need validation in larger sample sized studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. OBJECTIVE: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. METHODS: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1:99 (95% CI: 1.06, 3.78) and OR=1:65 (95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase= -5:86% (95% CI: -9:91%, -1:63%) and percent median change per log10-unit increase= -4:75% (95% CI: -8:16%, -0:61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1:26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640). CONCLUSIONS: Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. Methods: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. Results: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. Conclusions: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia. [ABSTRACT FROM AUTHOR]