γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet.

BACKGROUND: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.

Need for therapeutic escalation in patients with refractory ulcerative proctitis: Results from the PROCU study of the ENEIDA registry.

BACKGROUND: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. METHODS: We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. RESULTS: From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. CONCLUSIONS: Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.

Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011). CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

Comparison of green solvents for the revalorization of orange by-products: Carotenoid extraction and in vitro antioxidant activity.

Orange peels contain a considerable number of bioactive compounds such as carotenoids, that can be used as ingredients in high-value products. The aim of this study was to compare orange peel extracts obtained with different green solvents (vegetable oils, fatty acids, and deep eutectic solvents (DES)). In addition, the chemical characterization of a new hydrophobic DES formed by octanoic acid and l-proline (C8:Pro) was performed. The extracts were compared in terms of carotenoid extraction, antioxidant activity by three methods, color, and environmental impact. The results confirmed that the mixture of C8:Pro is a DES and showed the highest carotenoid extraction (46.01 µg/g) compared to hexane (39.28 µg/g). The antioxidant activity was also the highest in C8:Pro (2438.8 µM TE/mL). Finally, two assessment models were used to evaluate the greenness and sustainability of the proposed extractions. These results demonstrated the potential use of orange peels in the circular economy and industry.

A Population-Based Cross-Sectional Study of Paediatric Coeliac Disease in Catalonia Showed a Downward Trend in Prevalence Compared to the Previous Decade.

(1) Background: Previous studies showed an increased prevalence and incidence of coeliac disease (CD) over time. The objective is to ascertain whether the CD prevalence in Catalonia (a region of Southern Europe) among children aged 1-5 is as high as previously found in 2004-2009; (2) Methods: From 2013 to 2019, 3659 subjects aged 1-5 years were recruited following the previously used methodology. Factors with a potential impact on CD prevalence were investigated; (3) Results: In 2013-2019, 43/3659 subjects had positive serology, giving a standardised seroprevalence of 12.55/1000 (95% CI: 8.92; 17.40), compared to 23.62 (13.21; 39.40) in 2004-2007. The biopsy-proven crude prevalence was 7.92/1000 (95% CI: 5.50; 11.30), and the crude prevalence based on ESPGHAN criteria was 8.74/1000 (95% CI: 6.20-12.30). In contrast to 2004-2009, we did not find differences in the seroprevalence rates between 1 and 2 years vs. 3 and 4 years of age (age percentage of change -7.0 (-29.5; 22.8) vs. -45.3 (-67.5; -8.0)). Rotavirus vaccination was the most remarkable potential protective factor (48% vs. 9% in 2004-2009; p < 0.0001), but not the time of gluten introduction. (4) Conclusion: The present study did not confirm a worldwide CD prevalence increase and emphasizes the need to perform prevalence studies over time using the same methodology in the same geographical areas.

Regulación afectiva y simbolización: Estudio comparativo entre niños oyentes y no oyentes en edad preescolar / Affect regulation and symbolization: A comparative study between hearing impaired and hearing non impaired preescholers and their mothers

A través de diversos proyectos de investigación realizados entre 2002 y 2012, nuestro equipo viene construyendo puentes entre conceptos psicoanalíticos y los descubrimientos provenientes de la investigación en interacciones tempranas. Si bien la madre cumple un rol crucial en la regulación afectiva del bebé en los primeros meses, este rol se va complejizando a medida que se va ampliando el mundo afectivo y representacional a lo largo del desarrollo. En este trabajo se presenta un estudio comparativo sobre las modalidades de juego y las temáticas que caracterizan el contenido del juego en interacciones madre-niño preescolar oyente y con restricciones auditivas. Encontramos diferencias en relación a las variables estudiadas: nivel de simbolización y temáticas desplegadas -en particular cabe destacar el mayor despliegue de juego simbólico complejo en niños oyentes- que pueden aportar nuevas perspectivas para el diagnóstico y las estrategias posibles en el trabajo preventivo y clínico con niños con discapacidad auditiva.

Through various research projects conducted between 2002 and 2012, our team has been building bridges between psychoanalytical concepts and indings from research on early interactions. Although the mother plays a crucial role in infant's affect regulation in the irst months, this role grows in complexity as the infant's affective world widens throughout development. This paper presents a study on the modalities of play and the themes that characterize playing in mother- preescholer child interactions, comparing hearing and hearing impaired children. Our approach proposes a view that considers three dimensions of play: the child intrasubjective realm, adult intrasubjectve realm, and the interaction between mother and child. Playing themes are also explored. We found interesting differences regarding the studied variables. In particular it should be noted the higher proportion of complex symbolic play in hearing children. This indings can provide new perspectives for diagnosis and possible strategies in clinical and preventive work with children with hearing impairment.

El jugar en la relación madre-hijo y los procesos de simbolización en la infancia / Playing within mother-infant relationship and symbolisation processes in infancy

El juego madre-infante es un espacio primordial de despliegue vincular en el cual el niño transita desde un sentimiento de ilusión, omnipotencia y control a un sentido de realidad exterior (Winnicott, 1971). Relacionado con el placer, el jugar permite desarrollar representaciones de sí mismo y contribuye al sentido de agencia. Asimismo, la incorporación de objetos en la interacción ha mostrado complejizar los encuentros y desencuentros diádicos (Tronick, 1998). En este trabajo presentaremos resultados obtenidos en el programa de investigación longitudinal que realizamos desde el año 2002 (UBACyT P 803, P 806) en el cual mediante codificación microanalítica de videofilmaciones y entrevistas maternas, estudiamos el pasaje de la regulación afectiva diádica a la autorregulación infantil resaltando el papel del juego como moderador de los afectos, mediador en el intercambio vincular y antecedente de los procesos de simbolización en el niño. También presentamos una articulación con la teoría de Winnicott donde resaltamos el pasaje de "jugar a solas en presencia de otro" y "jugar juntos en una relación".

Mother-infant play activity offers a space where the relationship allows the child to move from a feeling of illusion, omnipotence and control towards a sense of external reality (Winnicott, 1971). Linked to feelings of joy and pleasure the child's play activity contributes to self-afirmation, to the construction of a sense of agency and to the development of self-representations. Also the inclusion of objects into the interaction ads complexity to the dyadic matches and mismatches (Tronick, 1998). In this paper we present results obtained in our research program (UBACyT P 803, P 806) which, through microanalytic analysis of videotaped interactive episodes and interviewing with the mother, we studied the transition from dyadic affective regulation to infant's self-regulation. We emphasize the role of playing activity to moderate affects, mediate in mother-infant interaction and as a precedent of symbolisation processes. Also, a theoretical articulation with Winnicotts' theory about playing activity is presented, where we focus on the movement from "playing alone in the presence of other" to "playing together within a relationship".

Los inicios del juego en la primera infancia y su relación con la regulación afectiva diádica y la autorregulación de los infantes / The beginnings of play in infancy and its relation with dyadic affective regulation and the infant self-regulation

Presentamos un programa de investigación longitudinal sobre 48 díadas madre-niño a los 6 meses y un seguimiento de 24 de las mismas a los 4/5 años que estudia el pasaje de la regulación afectiva diádica a la autorregulación en los niños (UBACyT P806). Se incluye una revisión teórica sobre la función del juego en la estructuración psíquica. El microanálisis de la interacción a los 6 meses mostró diferencias muy marcadas entre interacción cara a cara y juego libre con juguetes en cuanto a los recursos de autorregulación afectiva de los infantes. Se encontró, también una relación entre las variables de autoestima y funcionamiento reflexivo de las madres y las conductas de exploración lúdica con juguetes observada en los infantes. Estos resultados resaltan el lugar del juego con objetos como mediatizador en el logro de la transición de la regulación afectiva diádica a la autorregulación afectiva.

The present program is a follow up research on 48 mother-infant dyads studied when the infants were 6 months old and 24 of the same sample were studied at 4/5 years old about the transition between dyadic affective regulation and infant affective self regulation (UBACyT P806). A theoretical revision on the role of play in psychic development is included. Microanalysis showed differences between face to face interaction and free play interaction at 6 months regarding infant's self-regulatory resources. We also found a relationship between the variables maternal self esteem and reflective function in the mothers, and the exploratory play behaviors observed in the infants. These results underscore the role of play with toys as mediating factor in the transition from dyadic affect regulation to affective self-regulation.