Large scale sampling of Mexican maize landraces for the presence of transgenes.

The presence and levels of transgenic maize in Mexico and the effect this could have on local landraces or closely related species such as teosinte has been the subject of several previous reports, some showing contrasting results. Cultural, social and political factors all affect maize cultivation in Mexico and although since 1998 there has been a moratorium on the commercial cultivation of transgenic maize, Mexico imports maize, mainly from the USA where transgenic cultivars are widely grown. Additionally extensive migration between rural areas in Mexico and the USA and customs of seed exchange between farmers may also play an unintentional role in the establishment of transgenic seed. A comprehensive study of all Mexican maize landraces throughout the country is not feasible, however this report presents data based on analysis of 3204 maize accessions obtained from the central region of Mexico (where permits have never been authorized for cultivation of transgenic maize) and the northern region (where for a short period authorization for experimental plots was granted). The results of the study confirm that transgenes are present in all the geographical areas sampled and were more common in germplasm obtained in the northern region. However, there was no evidence that regions where field trials had been authorized showed higher levels of transgene presence or that the morphology of seed lots harboring transgenic material was significantly modified in favor of expected transgenic phenotypes.

Crop forcing technique and irrigation strategy modified the content and phenolic profile of cv. Tempranillo grape berries grown in a semi-arid climate.

BACKGROUND: Climate change modifies the content and phenolic profiles of grapes and wines. It is known that high temperatures, related to climate change, reduce anthocyanins and procyanidin (catechin and tannin) compounds accumulated in the berries. In recent years, with the aim of improving the phenolic composition of the berries, the technique of crop forcing has been proposed to delay grape ripening to a more favourable period of temperatures. RESULTS: In this study, crop forcing was applied to cv. Tempranillo vines on two different dates, after flowering (F1) and after fruit set (F2), and compared to a treatment control (NF, without forcing). Additionally, as a secondary factor, two irrigation strategies were established in each treatment: irrigation with no water stress, and a pre-veraison deficit irrigation. The study was carried out in three consecutive years (2017-2019). For most of the parameters analysed, no interaction was found. Therefore, for these parameters, the effect of each of these techniques was investigated independently. Regardless of the irrigation strategy, F2 berries achieved higher contents of catechins and anthocyanins than NF berries. Each year, regardless of the irrigation strategy, crop forcing increased the content of monoglucoside forms, and had a positive effect on the total content of malvidin, petunidin, delphinidin, peonidin and malvidin derivatives, but only affected acetyl and coumaryl forms in 2017. However, the effect of irrigation strategy was less significant and consistent, being more dependent on the vintage. CONCLUSION: Regardless of vine water status, crop forcing technique applied after fruit set could be used by vine growers to delay ripening of the grapes and thus achieve an increase in the anthocyanin characteristics of the grapes. © 2023 Society of Chemical Industry.

What role do endogenous retroviruses play in domestic cats infected with feline leukaemia virus?

Feline leukaemia virus (FeLV) is a retrovirus that infects domestic and wild cats around the world. FeLV infection is associated with the development of neoplasms, bone marrow disorders and immunosuppression. Viral subgroups arise from mutations in the FeLV genome or from recombination of FeLV with ancestral endogenous retroviruses in the cat genome. The retroviral endogenisation process has allowed generation of a diversity of endogenous viruses, both functional and defective. These elements may be part of the normal functioning of the feline genome and may also interact with FeLV to form recombinant FeLV subgroups, enhance pathogenicity of viral subgroups, or inhibit and/or regulate other retroviral infections. Recombination of the env gene occurs most frequently and appears to be the most significant in terms of both the quantity and diversification of pathogenic effects in the viral population, as well as affecting cell tropism and types of disease that occur in infected cats. This review focuses on available information regarding genetic diversity, pathogenesis and diagnosis of FeLV as a result of the interaction between endogenous and exogenous viruses.

Emergency visits and mortality caused by ischemic heart disease attributable to fine particulate matter during the COVID-19 pandemic in Chile.

POSITION DU PROBLèME: Le confinement mis en place au deuxième trimestre 2020 a entrainé une amélioration de la qualité de l'air de Santiago, capitale et plus grande ville du Chili, caractérisée par de fortes concentrations en particules fines PM2,5 liées, en grande partie, au trafic routier. L'objectif était de mettre en évidence une potentielle réduction des visites aux urgences pour infarctus du myocarde aigu (IDM) et des décès dus à une cardiopathie ischémique (CPI) attribuable à l'émission de PM2,5, en comparant les périodes équivalentes de 2019 et de 2020. MéTHODES: À Santiago, la surveillance de la qualité de l'air se fait grâce à neuf moniteurs situés dans neuf communes différentes : Cerro Navia, Cerrillos, El Bosque, Pudahuel, Independencia, La Florida, Quilicura, Santiago centre-ville et Las Condes (classées de la plus haute à la plus basse en matière de pauvreté multidimensionnelle). La concentration moyenne quotidienne de PM2,5 a été décrite avec des séries temporelles, et les visites aux urgences pour IDM et les décès dus à une CPI ont été analysés de façon trimestrielle pour chaque année. Pour estimer l'impact de l'excès de PM2,5, les fractions de risque attribuables (FRA) pour les visites aux urgences pour IDM et les décès pour CPI ont été calculées. RéSULTATS: La moyenne quotidienne des PM2,5 a diminué dans huit des neuf communes de Santiago. Cependant, la réduction n'a été significative que dans trois communes. Les visites aux urgences pour IDM et les décès par CPI attribuables aux PM2,5 ont diminué légèrement mais significativement dans ces trois communes. Les FRA dans les autres communes sont restées similaires à 2019. CONCLUSIONS: Une réduction significative de la FRA des PM2,5 pour les décès par CPI et les visites aux urgences d'IDM n'a été observée que dans les communes avec une réduction significative de la concentration quotidienne moyenne de PM2,5 pendant la pandémie de COVID-19.

Epigenetic regulation of TLR2-mediated periapical inflammation.

AIM: To determine the methylation pattern of TLR2 gene promoter and its association with the transcriptional regulation of periapical inflammatory and angiogenic responses in symptomatic and asymptomatic forms of apical periodontitis. METHODOLOGY: In this cross-sectional study, apical lesions were obtained from volunteers with asymptomatic apical periodontitis (AAP) (n = 17) and symptomatic apical periodontitis (SAP) (n = 17) scheduled for tooth extraction, and both total RNA and DNA were extracted. DNA was bisulfite-treated, a region of CpG island within the TLR2 gene was amplified by qPCR and the products were sequenced. Additionally, the mRNA expression of TLR2, TLR4, IL-6, IL-12, TNFalpha, IL-23, IL-10, TGFbeta, VEGFA and CDH5 was analysed by qPCR. The data were analysed with chi-square tests, Mann-Whitney or unpaired t-tests, and Spearman´s correlation; variable adjustments were performed using multiple linear regression (P < 0.05). RESULTS: TLR2 depicted a hypomethylated DNA profile at the CpG island in SAP when compared with AAP, along with upregulated expression of TLR2, with pro-inflammatory cytokines IL-6 and IL-23, and the angiogenesis marker CDH5 (P < 0.05). TLR2 methylation percentage negatively correlated with mRNA levels of IL-23 and CDH5 in apical periodontitis. Lower methylation frequencies of single CpG dinucleotides -8 and -10 localized in close proximity to nuclear factor κB (NFκB) binding within the TLR2 promoter were identified in SAP versus AAP (P < 0.05). Finally, unmethylated -10 and -8 single sites demonstrated up-regulation of IL-23, IL-10 and CDH5 transcripts compared to their methylated counterparts (P < 0.05). CONCLUSIONS: TLR2 gene promoter hypomethylation was linked to transcriptional activity of pro-inflammatory cytokines and angiogenic markers in exacerbated periapical inflammation. Moreover, unmethylated single sites in close proximity to NFκB binding were involved in active transcription of IL-23, IL-10 and CDH5.

Effect of Landscape Changes on Water Quality and Health Status of Heptapterus mustelinus (Siluriformes, Heptapteridae).

Substances derived from anthropogenic activities induce changes in the physical and chemical characteristics of the aquatic environment. Physicochemical and biological studies are necessary to understand how changes in landscape affect the health of the aquatic environment. The main goal of this study was to evaluate how the landscape at different spatial scales affects (1) water quality and (2) the health status of Heptapterus mustelinus, based on several biomarkers. During the dry season, individuals were caught in three sites with different degrees of anthropogenic activity. The quality of the terrestrial environment was assessed using the Riparian Quality and Land Use Indices. The water quality condition was evaluated using a water quality index, and pesticides and pharmaceuticals were measured in water. The following biomarkers were analyzed in the fish: general health status (Condition Factor, Hepatosomatic index and energetic costs), enzymatic activity (GST, CAT, AchE), carbonyl content in proteins and histopathological responses in liver and gills. The most impacted sites by the presence of pesticides showed more alterations in the surrounding landscape; specially, changes in the riparian area. In this area, biomarkers denoted more damage than in sites with protected riparian zone. Conservation status of riparian ecosystems is crucial in the determination of rivers ecological quality. Our results demonstrate the importance of monitoring the environmental quality through an integrated analysis, using native fish to understand the effects of human activities on the biota.

Variability among strains of Aspergillus section Nigri with capacity to degrade tannic acid isolated from extreme environments.

Tannins are polyphenolic compounds that cause astringent flavor and turbidity in food. Tannase is an enzyme that catalyzes the hydrolysis of tannins and is used in food industry. This study was conducted to determine the genetic variability and the tannase alleles variation in fungal strains isolated from soil and plants at five extreme areas of Coahuila, México. Two screening assays under 1 and 20 % of tannic acid were performed, with the isolations. In these assays, it was possible to identify 756 and 128 fungal strains, respectively. The major fungal variability was observed in "Cuatro Ciénegas" with 26 strains. The microorganisms were distributed in 11 groups, which correspond to Aspergillus section Nigri. AN7 and AN1 groups showed the major number of isolates from "Paila" and "Cuatro Ciénegas" locations, respectively. In the last location, the major diversity and specific richness were found. But in "Ojo Caliente," tannase allele conservations were observed.

Low-level arsenic exposure during pregnancy and its association with postpartum depression: A cohort study of women from Arica, Chile.

BACKGROUND: While the relationship between inorganic arsenic exposure and psychological impairment has been studied previously, the association between low-level arsenic exposure during pregnancy and postpartum depression has not yet been examined. The objective is to estimate the association between low-level arsenic exposure during pregnancy and the Edinburgh score. METHODS: A sample of 223 women was collected from five public health services in Arica, Chile. Participation was voluntary and written consent was mandatory. Sociodemographic data related to arsenic exposure and urine samples for total inorganic arsenic assessments were collected during the second trimester. Postpartum depression symptoms were estimated by the Edinburgh Postpartum Depression scale. We examined descriptive statistics and ran multiple linear regressions. The modifying effect of age and depression history was evaluated separately. RESULTS: The median for total urinary inorganic arsenic was 14.6µg/L (range: 2-69.2µg/L), the median for postpartum depression score was 8 points (range: 0-27 points) and 20.6% of women were considered as postpartum depressed. For women older than 25years old without depression history, the adjusted coefficient for the total urinary natural logarithm of inorganic arsenic in multiple linear regressions was -2.51 (95% CI: -4.54, -0.48; P-value=0.02). For women older than 25years old with a depression history, this value was 2.09 (95% CI: -0.90, 5.08; P-value=0.16). CONCLUSIONS: In this cohort, the number of children, physical perception, depression history, stressful maternity, and age were associated with postpartum depression score. The Edinburgh score was associated with inorganic arsenic in women older than 25years without depression history.

Long non-coding RNAs are major contributors to transcriptome changes in sunflower meiocytes with different recombination rates.

BACKGROUND: Meiosis is a form of specialized cell division that marks the transition from diploid meiocyte to haploid gamete, and provides an opportunity for genetic reassortment through recombination. Experimental data indicates that, relative to their wild ancestors, cultivated sunflower varieties show a higher recombination rate during meiosis. To better understand the molecular basis for this difference, we compared gene expression in male sunflower meiocytes in prophase I isolated from a domesticated line, a wild relative, and a F1 hybrid of the two. RESULTS: Of the genes that showed differential expression between the wild and domesticated genotypes, 63.62 % could not be identified as protein-coding genes, and of these genes, 70.98 % passed stringent filters to be classified as long non-coding RNAs (lncRNAs). Compared to the sunflower somatic transcriptome, meiocytes express a higher proportion of lncRNAs, and the majority of genes with exclusive expression in meiocytes were lncRNAs. Around 40 % of the lncRNAs showed sequence similarity with small RNAs (sRNA), while 1.53 % were predicted to be sunflower natural antisense transcripts (NATs), and 9.18 % contained transposable elements (TE). We identified 6895 lncRNAs that are exclusively expressed in meiocytes, these lncRNAs appear to have higher conservation, a greater degree of differential expression, a higher proportion of sRNA similarity, and higher TE content relative to lncRNAs that are also expressed in the somatic transcriptome. CONCLUSIONS: lncRNAs play important roles in plant meiosis and may participate in chromatin modification processes, although other regulatory functions cannot be excluded. lncRNAs could also be related to the different recombination rates seen for domesticated and wild sunflowers.

Glucocorticoid Receptors, Brain-Derived Neurotrophic Factor, Serotonin and Dopamine Neurotransmission are Associated with Interferon-Induced Depression.

BACKGROUND: The role of inflammation in mood disorders has received increased attention. There is substantial evidence that cytokine therapies, such as interferon alpha (IFN-alpha), can induce depressive symptoms. Indeed, proinflammatory cytokines change brain function in several ways, such as altering neurotransmitters, the glucocorticoid axis, and apoptotic mechanisms. This study aimed to evaluate the impact on mood of initiating IFN-alpha and ribavirin treatment in a cohort of patients with chronic hepatitis C. We investigated clinical, personality, and functional genetic variants associated with cytokine-induced depression. METHODS: We recruited 344 Caucasian outpatients with chronic hepatitis C, initiating IFN-alpha and ribavirin therapy. All patients were euthymic at baseline according to DSM-IV-R criteria. Patients were assessed at baseline and 4, 12, 24, and 48 weeks after treatment initiation using the Patient Health Questionnaire (PHQ), the Hospital Anxiety and Depression Scale (HADS), and the Temperament and Character Inventory (TCI). We genotyped several functional polymorphisms of interleukin-28 (IL28B), indoleamine 2,3-dioxygenase (IDO-1), serotonin receptor-1A (HTR1A), catechol-O-methyl transferase (COMT), glucocorticoid receptors (GCR1 and GCR2), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5) genes. A survival analysis was performed, and the Cox proportional hazards model was used for the multivariate analysis. RESULTS: The cumulative incidence of depression was 0.35 at week 24 and 0.46 at week 48. The genotypic distributions were in Hardy-Weinberg equilibrium. Older age (p = 0.018, hazard ratio [HR] per 5 years = 1.21), presence of depression history (p = 0.0001, HR = 2.38), and subthreshold depressive symptoms at baseline (p = 0.005, HR = 1.13) increased the risk of IFN-induced depression. So too did TCI personality traits, with high scores on fatigability (p = 0.0037, HR = 1.17), impulsiveness (p = 0.0200 HR = 1.14), disorderliness (p = 0.0339, HR = 1.11), and low scores on extravagance (p = 0.0040, HR = 0.85). An interaction between HTR1A and COMT genes was found. Patients carrying the G allele of HTR1A plus the Met substitution of the COMT polymorphism had a greater risk for depression during antiviral treatment (HR = 3.83) than patients with the CC (HTR1A) and Met allele (COMT) genotypes. Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype. Moreover, functional variants of the GCR1 (GG genotype: p = 0.0436, HR = 1.88) and BDNF genes (Val/Val genotype: p = 0.0453, HR = 0.55) were associated with depression. CONCLUSIONS: The results of the study support the theory that IFN-induced depression is associated with a complex pathophysiological background, including serotonergic and dopaminergic neurotransmission as well as glucocorticoid and neurotrophic factors. These findings may help to improve the management of patients on antiviral treatment and broaden our understanding of the pathogenesis of mood disorders.

Do physicians correctly calculate thromboembolic risk scores? A comparison of concordance between manual and computer-based calculation of CHADS2 and CHA2 DS2 -VASc scores.

BACKGROUND: Clinical risk scores, CHADS2 and CHA2 DS2 -VASc scores, are the established tools for assessing stroke risk in patients with atrial fibrillation (AF). AIM: The aim of this study is to assess concordance between manual and computer-based calculation of CHADS2 and CHA2 DS2 -VASc scores, as well as to analyse the patient categories using CHADS2 and the potential improvement on stroke risk stratification with CHA2 DS2 -VASc score. METHODS: We linked data from Atrial Fibrillation Spanish registry FANTASIIA. Between June 2013 and March 2014, 1318 consecutive outpatients were recruited. We explore the concordance between manual scoring and computer-based calculation. We compare the distribution of embolic risk of patients using both CHADS2 and CHA2 DS2 -VASc scores RESULTS: The mean age was 73.8 ± 9.4 years, and 758 (57.5%) were male. For CHADS2 score, concordance between manual scoring and computer-based calculation was 92.5%, whereas for CHA2 DS2 -VASc score was 96.4%. In CHADS2 score, 6.37% of patients with AF changed indication on antithrombotic therapy (3.49% of patients with no treatment changed to need antithrombotic treatment and 2.88% of patients otherwise). Using CHA2 DS2 -VASc score, only 0.45% of patients with AF needed to change in the recommendation of antithrombotic therapy. CONCLUSION: We have found a strong concordance between manual and computer-based score calculation of both CHADS2 and CHA2 DS2 -VASc risk scores with minimal changes in anticoagulation recommendations. The use of CHA2 DS2 -VASc score significantly improves classification of AF patients at low and intermediate risk of stroke into higher grade of thromboembolic score. Moreover, CHA2 DS2 -VASc score could identify 'truly low risk' patients compared with CHADS2 score.

Chemotherapy in recurrent advanced non-small-cell lung cancer after adjuvant chemotherapy.

INTRODUCTION: Despite adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (nsclc), many will subsequently relapse. We investigated treatment choices at relapse and assessed the effect of palliative platinum doublet systemic therapy in this population. METHODS: With research ethics board approval, we performed a retrospective chart review of all patients with resected nsclc who received adjuvant systemic therapy from January 2002 until December 2008 at our institution. The primary outcome was the response rate to first-line palliative systemic therapy among patients who relapsed. RESULTS: We identified 176 patients who received adjuvant platinum doublet systemic therapy (82% received cisplatin-vinorelbine). In the 85 patients who relapsed (48%), median time to relapse was 18.5 months (95% confidence interval: 15 months to 21.3 months). Palliative systemic therapy was given in 43 patients. Of those 43 patients, 25 (58%) were re-challenged with platinum doublet systemic therapy, with a response rate of 29% compared with 18% in 18 patients who received other systemic therapy (p = 0.48). We observed a trend toward an increased clinical benefit rate (complete response + partial response + stable disease) in patients who were treated with a platinum doublet (67% vs. 41%, p = 0.12). Median overall survival (os) from relapse was 15.3 months in patients receiving palliative systemic therapy and 7.8 months in those receiving best supportive care alone. Compared with patients treated with non-platinum regimens, the platinum-treated group experienced longer survival after relapse (18.4 months vs. 9.7 months, p = 0.041). CONCLUSIONS: In patients previously treated with adjuvant systemic therapy, re-treatment with platinum doublet chemotherapy upon relapse is feasible. Moreover, compared with patients receiving other first-line systemic therapy, patients receiving platinum doublets experienced higher response rates and significantly longer survival.

Involvement of the -420C>G RETN polymorphism in myocardial fibrosis in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis. HCM is an autosomal-dominant disease caused by more than 400 mutations in sarcomeric genes. Changes in nonsarcomeric genes contribute to its phenotypic heterogeneity. Cardiac fibrosis can be studied using late gadolinium enhancement (LGE) cardiac magnetic resonance imaging. We evaluated the potential role of two polymorphisms in nonsarcomeric genes on interstitial fibrosis in HCM. MATERIALS AND METHODS: Two polymorphisms in nonsarcomeric genes [ACE (deletion of 287 bp in the 16th intron) and RETN (-420C>G)] were analysed in 146 HCM patients. Cardiac fibrosis was assessed using LGE to determine the number of affected segments. RESULTS: Allelic frequencies in ACE and RETN polymorphisms were consistent with the Hardy-Weinberg equilibrium (both P > 0.05). We found that the presence of the polymorphic allele in the -420C>G RETN polymorphism was independently associated with the number of affected segments of LGE (P = 0.038). Increased circulating resistin concentration, measured by enzyme-linked immunosorbent assay, was associated with a higher degree of cardiac fibrosis. Myocardial fibrosis, assessed by Masson's trichrome staining, was associated with the -420C>G RETN polymorphism in 46 tissue samples obtained by septal myectomy (P = 0.044). CONCLUSIONS: The -420C>G RETN polymorphism was independently associated with the degree of cardiac fibrosis, assessed by LGE, in patients with HCM. In addition, there was an association between the polymorphism and the circulating resistin levels as well as with myocardial fibrosis in tissues obtained by myectomy. Investigating the physiological implication of the RETN polymorphism in HCM in combination with the use of imaging technologies might help to establish the severity of disease in patients with HCM.

Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Effect of UV radiation on habitat selection by Girella laevifrons and Graus nigra (Kyphosidae).

The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the same pools but exhibit different activity levels and diets was measured: the highly active omnivorous Girella laevifrons and the cryptic carnivorous Graus nigra. Individuals of each species were acclimated to a tank divided in three sections with different illumination; no light (NL), ultraviolet light (UV) and white light (WL), and the time spent and number of visits to each section were recorded. Although both species preferred the NL section, G. laevifrons spent more time in UV and less time in WL compared with G. nigra; G. laevifrons also displayed higher number of visits to UV, suggesting a different tendency in space use in response to UV exposure in intertidal fishes.

Erratum: Tumour inflammatory response: adding fuel to the fire?

[This corrects the article on p. 7 in vol. 22, PMID: 25684982.].

Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.

Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.

Biomarkers in atrial fibrillation: an overview.

Atrial fibrillation (AF) confers a raised risk of stroke and death, and this risk of adverse events is increased by the coexistence of other cardiovascular risk factors. The pathophysiology of AF is complex, involving the role of inflammation, structural remodelling with apoptosis, inflammation or fibrosis. These changes confer a prothrombotic or hypercoagulable state in this arrhythmia. Despite being easy to use for decision-making concerning oral anticoagulant therapy in AF, clinical risk scores used for stratification have shown modest capability in predicting thromboembolic events, and biomarkers may improve our identification of 'high risk' patients. Biomarkers, whether measured in the peripheral blood, urine or imaging-based may improve our knowledge of the pathophysiology of AF. Importantly these biomarkers could help in the assessment of AF prognosis. The aim of this review was to summarise the published data about biomarkers studied in AF, with focus on data from randomised prospective clinical trials and large community-based cohorts. We will also review the application of these biomarkers to prognosis on the main schemes used to help stratify risk in AF.

Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients.

AIM: Risk stratification in acute coronary syndrome without ST-segment elevation (NSTE-ACS) and troponin-negative remains a challenge. We evaluated the value of interleukin-6 (IL-6) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognosis assessment of low-moderate risk NSTE-ACS and troponin-negative, and whether these biomarkers could improve the predictive performance of the established thrombolysis in myocardial infarction (TIMI) risk score. METHODS: A total of 212 low-moderate risk patients with NSTE-ACS and troponin-negative were prospectively studied. Clinical follow up at 6 months was performed for adverse endpoints. RESULTS: A total of 28 patients (13.5%) presented adverse clinical events. Those with adverse clinical events were associated with higher levels of IL-6 [8.58 (5.13-20.95) ng/l vs. 6.12 (4.16-9.14) ng/l, p = 0.043] and NT-proBNP [275.3 (108.6-548.2) ng/l vs. 126.8 (55.97-430.20) ng/l, p = 0.046]. In moderate risk group, we observed a higher event rate in patients with troponin-negative but elevated levels of IL-6 (p = 0.024). Only elevated IL-6 (> 12.40 ng/l) was an independent predictor of adverse outcomes [hazard ratios: 3.62, 95% confidence interval (CI) 1.69-7.75, p = 0.001]. The addition of IL-6 and history of ischaemic heart disease (IHD) to TIMI risk score significantly improved both the discrimination (integrated discrimination improvement, p = 0.003) and reclassification (Clinical Net reclassification improvement, p = 0.010) of the model for adverse events. CONCLUSIONS: Interleukin-6 is an independent predictor of adverse events in low-moderate risk patients with NSTE-ACS and troponin-negative. Its use identifies a higher risk population in moderate-risk patients. This provides together with history of IHD a better discrimination and reclassification beyond that achieved with clinical risk variables from TIMI risk score in these patients.

Effects of the synthetic estrogen 17α-ethinylestradiol on aromatase expression, reproductive behavior and sperm quality in the fish Jenynsia multidentata.

The synthetic estrogen 17α-ethynylestradiol (EE2) has been increasingly detected in sewage effluents in the last two decades. The aim of the present study was determined if EE2 exposure adversely affected reproduction in internally fertilizing fish species Jenynsia multidentata. Sexual behavior, brain and gonadal aromatase expression as well as sperm quality were evaluated. The brain aromatase expression, reproductive behavior, spermatozoa viability and gonadosomatic index were sensitive biomarkers of EE2 effects on this species. The condition factor, hepatosomatic index, gonadal aromatase expression, sperm count and sperm velocities were unaltered after EE2 exposure. The present work highlights the importance of using a combination of several biomarkers to study the effects of estrogenic compounds, especially when trying to link these results to potential population-level effects.