Genes involved in the metabolism of fatty acids and risk for Crohn's disease in children: a candidate gene study

Contexte - La prévalence de la maladie de Crohn (MC), une maladie inflammatoire chronique du tube digestif, chez les enfants canadiens se situe parmi les plus élevées au monde. Les interactions entre les réponses immunes innées et acquises aux microbes de l'hôte pourraient être à la base de la transition de l’inflammation physiologique à une inflammation pathologique. Le leucotriène B4 (LTB4) est un modulateur clé de l'inflammation et a été associé à la MC. Nous avons postulé que les principaux gènes impliqués dans la voie métabolique du LTB4 pourrait conférer une susceptibilité accrue à l'apparition précoce de la MC. Dans cette étude, nous avons exploré les associations potentielles entre les variantes de l'ADN des gènes ALOX5 et CYP4F2 et la survenue précoce de la MC. Nous avons également examiné si les gènes sélectionnés montraient des effets parent-d'origine, influençaient les phénotypes cliniques de la MC et s'il existait des interactions gène-gène qui modifieraient la susceptibilité à développer la MC chez l’enfant. Méthodes – Dans le cadre d’une étude de cas-parents et de cas-témoins, des cas confirmés, leurs parents et des contrôles ont été recrutés à partir de trois cliniques de gastro-entérologie à travers le Canada. Les associations entre les polymorphismes de remplacement d'un nucléotide simple (SNP) dans les gènes CYP4F2 et ALOX5 ont été examinées. Les associations allélique et génotypiques ont été examinées à partir d’une analyse du génotype conditionnel à la parenté (CPG) pour le résultats cas-parents et à l’aide de table de contingence et de régression logistique pour les données de cas-contrôles. Les interactions gène-gène ont été explorées à l'aide de méthodes de réduction multi-factorielles de dimensionnalité (MDR). Résultats – L’étude de cas-parents a été menée sur 160 trios. L’analyse CPG pour 14 tag-SNP (10 dans la CYP4F2 et 4 dans le gène ALOX5) a révélé la présence d’associations alléliques ou génotypique significatives entre 3 tag-SNP dans le gène CYP4F2 (rs1272, p = 0,04, rs3093158, p = 0.00003, et rs3093145, p = 0,02). Aucune association avec les SNPs de ALOX5 n’a pu être démontrée. L’analyse de l’haplotype de CYP4F2 a montré d'importantes associations avec la MC (test omnibus p = 0,035). Deux haplotypes (GAGTTCGTAA, p = 0,05; GGCCTCGTCG, p = 0,001) montraient des signes d'association avec la MC. Aucun effet parent-d'origine n’a été observé. Les tentatives de réplication pour trois SNPs du gene CYP4F2 dans l'étude cas-témoins comportant 225 cas de MC et 330 contrôles suggèrent l’association dans un de ceux-ci (rs3093158, valeur non-corrigée de p du test unilatéral = 0,03 ; valeur corrigée de p = 0.09). La combinaison des ces deux études a révélé des interactions significatives entre les gènes CYP4F2, ALOX et NOD2. Nous n’avons pu mettre en évidence aucune interaction gène-sexe, de même qu’aucun gène associé aux phénotypes cliniques de la MC n’a pu être identifié. Conclusions - Notre étude suggère que la CYP4F2, un membre clé de la voie métabolique LTB4 est un gène candidat potentiel pour MC. Nous avons également pu mettre en évidence que les interactions entre les gènes de l'immunité adaptative (CYP4F2 et ALOX5) et les gènes de l'immunité innée (NOD2) modifient les risques de MC chez les enfants. D'autres études sur des cohortes plus importantes sont nécessaires pour confirmer ces conclusions.Background - The rates of Crohn’s disease (CD) a chronic inflammatory disease of the gastrointestinal tract, among Canadian children are the world’s highest. Interactions between the host microbial–innate-immune-responses are thought to underplay transition from physiological to pathological inflammation. Leukotriene B4 (LTB4) is a key modulator of inflammation and has been shown to be associated with CD. We postulated that key genes involved in the LTB4 metabolic pathway could confer susceptibility for early-onset CD. In this study we implemented a candidate gene approach to test for associations between DNA variants in the ALOX5 and CYP4F2 genes and early-onset of CD. We also explored whether the selected genes demonstrated parent-of-origin effects, influenced CD clinical phenotypes and whether there were gender-gene and gene-gene interactions that determined CD susceptibility. Methods – The study consisted of an exploratory phase (case-parent design) followed by a replication phase (case-control design). Confirmed cases, parents and controls were recruited from three tertiary gastroenterology clinics across Canada. Associations between tag-single nucleotide polymorphisms in the CYP4F2 and ALOX5 genes were examined. Allelic and/or genotype associations were examined using conditional on parental genotype (CPG) analysis for the case-parent data and contingency table and logistic regression for the case-control data. Gene-gene interactions were explored using multi-factor dimensionality reduction (MDR) methods. Results – The first phase of the study was based on 160 trios (case-parent design). CPG analysis for 14 tag-SNPs (i.e. 10 in the CYP4F2 and 4 in the ALOX5 gene, respectively) revealed significant allelic or genotypic associations between 3 tag-SNPs in the CYP4F2 gene (rs1272, p=0.04, rs3093158, p=0.00003, and rs3093145, p=0.02). No associations with ALOX5 tag-SNPs were evident. CYP4F2-haplotype analysis showed significant associations with CD (omnibus test p-value=0.035). Two specific haplotypes (GAGTTCGTAA, p=0.05; GGCCTCGTCG, p=0.001) showed evidence for association with CD. No parent-of-origin effects were observed. The second phase of the study retested the three CYP4F2 SNPs that showed association in the first stage and was based on 223 CD cases and 330 controls. Some indications of association with one SNP i.e. rs3093158 were present (genotypic uncorrected 1-sided p-value=0.03); however this genotype association did not withstand correction. Combining cases from the two phases of the study revealed significant interactions between the CYP4F2, ALOX and NOD2 genes. No gene-gender interactions were obvious nor were the study genes associated with specific clinical phenotypes of CD. Conclusions - Our study suggests that the CYP4F2, a key member of the LTB4 metabolic pathway is a potential candidate gene for CD. Furthermore there was evidence that interactions between adaptive immunity genes (CYP4F2 and ALOX5) and innate immunity genes (NOD2) genes modify risk for CD in children. Further studies on larger cohorts are required to confirm these findings

Interpersonal and Pet Attachment, Empathy toward Animals, and Anthropomorphism: An Investigation of Pet Owners in Romania

The current study investigates the associations between interpersonal and pet attachment (anxiety and avoidance dimensions), empathy toward animals, and anthropomorphism in the Romanian cultural context, where problems regarding the effectiveness of pet management programs are still being reported. A sample of 244 adult respondents, with a mean age of 32.9 years, mostly females (89.8%) and pet owners, completed standard instruments of interpersonal and pet attachment, empathy toward animals and anthropomorphism. In agreement with other studies in the field of human-animal interactions, our data indicate that female pet owners scored higher than male owners in empathy toward animals and the level of anthropomorphism. Dog owners scored higher in empathy toward animals and anthropomorphism, and lower in pet attachment avoidance compared to owners of other types of pets (cats, reptiles, birds, etc.). Our data indicate significant correlations between anxiety and avoidance dimensions of pet and interpersonal attachment. The level of anthropomorphism was positively associated with pet attachment anxiety and empathy toward animals, and negatively associated with pet attachment avoidance. A partial mediation of the relationship between pet attachment avoidance and anthropomorphism by empathy toward animals was found. Results are discussed from the perspective of considering empathy toward animals as an important variable to be addressed in humane education programs and in attachment-based counseling of current and future pet owners

THE STUDY OF ACCLIMATIZATION OF GRAPES OF MEDITERRANEAN ORIGIN TO THE WEATHER CONDITIONS OF THE WINE-GROWING REGIONS OF SEGARCEA

This study was carried out during 2019-2020 on plots belonging to the wine-growing areas of Segarcea, famous wine areas in point of extracting red wine with remarkable qualities in the south of the country. The significance of the work consists in improving the useful climate of the wi ne area of Segarcea by introducing into the culture beside black grapes varieties, renowned varieties like Feteascăneagră, Merlot, Cabernet-Sauvignon, Pinot noir, etc., other grape varieties of Mediteranean origin, such as Syrah and Marselan. The aim is to rigorously monitor the weather conditions with a direct impact on the soils with a production potential, observing the dynamics of its establishment and maturation index for each variety during the period studied

Gastroduodenal ulcer with bleeding – a reconsideration of therapy

Spitalul Clinic de Urgență Sfântul Pantelimon, București, România, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Complicația hemoragică a ulcerului gastroduodenal cunoaște o incidența în creștere în ultimii ani. Studiul își propune reevaluarea atitudinii terapeutice în cazul ulcerului gastroduodenal hemoragic, cu stabilirea unor criterii de gravitate în care intervenția chirurgicală se impune. Material si metode: Studiul analizează retrospectiv un număr de 337 de pacienți cu diagnosticul de ulcer gastroduodenal hemoragic, internați și tratați în Clinica Chirurgie a Spitalului Clinic de Urgență „Sf. Pantelimon”, în decurs de 3 ani, în perioada ian. 2008 – dec. 2010. S-au analizat datele din foile de observație, protocoale operatorii, rezultate histopatologice. Rezultate: Majoritatea hemoragiilor digestive superioare de cauză ulceroasă au fost rezolvate cu tratament medicamentos (278 bolnavi). La restul de 59 de pacienți a fost necesar un tratament chirurgical, dintre care la 43 pacienți intervenția a fost impusă de pierderea de sânge ce amenință viața, iar la 16 pacienți intervenția a fost impusă de criteriile de gravitate/criteriile prognostice: repetarea sângerarii la scurt timp, criterii endoscopice de gravitate, grupa de sânge rară, etc. La 32 de bolnavi s- au practicat rezecții gastrice subtotale cu diferite tipuri de anastomoză iar în 27 de cazuri s-a practicat ulceroexcizie și hemostaza in situ. Concluzii: Evoluția ascendentă a terapiei farmacologice și endoscopice a scăzut semnificativ necesitatea intervențiilor chirurgicale. Intervenția chirurgicală rămâne mijloc terapeutic util în cazurile cu sângerare masivă și în cazurile neglijate terapeutic.As a complication of gastroduodenal ulcer, bleeding is more and more frequent. The study aims to reevaluate the therapeutic approach together with the development of criteria recommending surgery. Material and methods: The study evaluates 337 patients diagnosed with gastroduodenal ulcer, complicated with bleeding, between January 2008 and December 2010. Data was collected from patient charts, operative recordings, histopathological results. Results: The majority of upper GI bleeding, following the development of an ulcer was managed with medical therapy (278 patients). The remaining 59 patients required surgery, imposed in 43 cases by life threatening blood loss, and in 16 by gravity/prognostic criteria: frequent recurrence of bleeding, endoscopic gravity criteria, rare blood group, etc. Subtotal gastrectomy with various types of anastomosis was performed in 32 cases while in the remaining 27 cases we performed the excision of the lesion and in situ hemostasis. Conclusions: The evolution of pharmacological and endoscopic management significantly reduced the necessity for surgery. Surgery remains a useful therapeutic tool in cases with massive bleeding and in neglected cases

Carotid paragangliomas: case report and imaging review

Background: Presentation of case reviews depicting the imaging characteristics of carotid paragangliomas, associated with a thorough analysis of the anatomical morphological features and the current therapeutic strategies.Materials and methods: We present the cases of 3 patients diagnosed with carotid paragangliomas in our clinic, illustrating diagnostic imaging elements by computer tomography (CT) and magnetic resonance imaging (MRI), but also the postoperative aspect of the carotid system, with respective anatomical, clinical and surgical considerations.Results: The imaging aspect of the carotid paragangliomas is characterised by a mass of soft tissue with intense contrast enhancement and with “salt and pepper” MRI appearance on conventional spin-echo sequences. The postoperative evolution of the patients included in the article was favourable, without any perioperative complications or signs of local tumour recurrence.Conclusions: Carotid paragangliomas are rare, often asymptomatic tumours, but with potential for increased malignancy, which raises the need for good knowledge of the cervical region pathology as well as the features of neuroendocrine tumours. CT and MRI examinations are essential for diagnosis, staging and, implicitly, for establishing the therapeutic strategy