Effects of early-life stress followed by access to stevia or sucralose during adolescence on weight gain, glycemia, and anxiety-related behaviors in male and female rats.

Early-life stress and subsequent high-calorie diets during adolescence are known to be risk factors for developing metabolic and psychological disorders. Although non-nutritive sweeteners such as stevia and sucralose have been a useful alternative to reduce sugar consumption, the effects of prolonged consumption of these sweeteners on metabolism and behavior in adolescents remain unclear. Here, we evaluated the effects of early-stress followed by access to stevia or sucralose during adolescence on weight gain, glycemia, and anxiety-related behaviors in male and female rats. During postnatal days (PNDs) 1-21, pups were separated twice a day, for 180 min each time, from their dam nest while non-separated pups served as controls. The pups were weaned, separated by sex and randomly distributed into the stevia, sucralose and water conditions. During PNDs 26-50, two bottles containing water and stevia or sucralose were placed in the animal home-cages, and body weight and blood glucose measures were scored. On PNDs 50 and 51, behavioral measures were obtained in the open-field test. Results showed that male rats consuming stevia reduced body weight gain, blood glucose and increased locomotion. Early-stress led to low blood glucose and alterations in anxiety and locomotion-related behaviors in a sex-dependent manner. Moreover, sucralose access during adolescence reversed the effects of early-stress on anxiety-related behaviors in female rats. The results suggest that the consumption of stevia and sucralose could be an alternative for the replacement of sugar-sweetened beverages, especially in adolescents who have had adverse early-life experiences.

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Evaluation of genetic variants associated with the risk of thiopurine-related pancreatitis: a case control study from ENEIDA registry.

BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled, 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis, and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Impact of a Moderate CYP3A4 Inducer (Bosentan) on Lurbinectedin Pharmacokinetics and Safety in Patients with Advanced Solid Tumors: An Open-Label, Two-Way, Crossover, Phase Ib Drug-Drug Interaction Study.

This open-label, two-way, crossover, phase Ib drug-drug interaction study investigated whether the pharmacokinetics (PKs) and safety profile of lurbinectedin (LRB) are affected by co-administration of a moderate CYP3A4 inducer (bosentan, BOS) in adult patients with advanced solid tumors. Eleven patients were randomly assigned to Sequence 1 (LRB + BOS in Cycle 1 [C1] and LRB alone in Cycle 2 [C2]) or Sequence 2 (LRB alone in C1 and LRB + BOS in C2), and finally, eight patients (four per sequence) were considered evaluable for PK assessment. LRB (3.2 mg/m2, 1 h [h], intravenous) was administered alone or combined with multiple BOS administration (125 mg/12 h oral; 5.5 days). Co-administration with BOS decreased the systemic total exposure (area under the curve, AUC) of LRB by 21% for AUC0-t and 20% for AUC0-∞ and increased clearance by 25%. Co-administration with BOS did not significantly modify the unbound plasma LRB PK parameters. BOS increased the conversion of LRB to its metabolite M1, with no changes on its metabolite M4. The LRB safety profile was consistent with the toxicities previously described for this drug. No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.

Nasolacrimal sac foreign body extraction using vitreoretinal forceps in 28 dogs.

PURPOSE: To describe a novel technique of nasolacrimal foreign body extraction in dogs by using a 20G vitreoretinal forceps introduced through the superior lacrimal punctum. METHODS: A retrospective review of the medical records of dogs with dacryocystitis due to nasolacrimal foreign bodies between the years 2001 and 2022 was performed. We recorded the breed, age, affected eye, type and number of foreign bodies, concomitant diseases, and the use of imaging techniques. All animals underwent the same procedure of a 20G vitreoretinal forceps insertion through the upper canaliculus reaching the lacrimal sac and retrograde extraction of the foreign bodies. RESULTS: A total of 28 dogs were included, 16 males and 12 females, with a mean (±SD) age of 4.7 (±3.2) years. The most common breeds were Wire-Haired Dachshund (4/28; 14.29%) and Labrador Retriever (3/28; 10.71%). Additional imaging techniques were used, such as orbital ultrasound in 13 cases (13/28; 46.43%) and computed tomography in one case (1/28; 3.57%). The most common type of foreign body retrieved was grass awns, although seeds and plant debris were also found. Dacryocystitis resolved after removal of the foreign body and appropriate medical therapy was ensured in all cases in the 1-month postprocedure follow-up. CONCLUSION: Extraction of nasolacrimal foreign bodies with vitreoretinal forceps is a novel, noninvasive, and easily applicable technique that, although not successful in all cases, can be attempted before performing more aggressive surgery.

Hidden Diversity in Eigenmannia (Gymnotiformes: Sternopygidae) Populations from Upper Paraná and Paraguay Rivers.

Eigenmannia is a highly diverse genus within the Sternopygidae family, comprising 30 species. Due to its complex taxonomy, molecular analyses have been crucial for species delimitation within this group. Therefore, the present study presents a genetic analysis using sequences of the mitochondrial gene cytochrome c oxidase subunit 1 (COI) in specimens previously identified through alpha taxonomy as E. correntes (with unpublished data), E. virescens, and E. trilineata, originating from various locations within the Upper Paraná and Paraguay River basins in Brazil. The molecular data confirm the taxonomic complexity of the genus, as individuals morphologically identified as E. virescens and E. trilineata shared the same haplotype (H52). Furthermore, the results of the species delimitation tests suggest that specimens morphologically identified as E. virescens belong to the species E. trilineata. In addition, samples morphologically identified as E. correntes may correspond to more than one Operational Taxonomic Units (OTUs). Furthermore, the intraspecific Kimura-2-parameter (K2P) distances within the different studied populations are significant. This study has contributed valuable information about genetic diversity in Eigenmannia, emphasizing the importance of using integrative analyses to resolve taxonomic conflicts within the group. It also supports biogeographical studies and assists in biodiversity conservation efforts.

Hematological Composite Scores in Patients with Inflammatory Bowel Disease.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients-130 Crohn's (CD) disease and 67 ulcerative colitis (UC)-and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.

Comparative genomic analysis of Mycoplasma related to cell culture for infB gene-based loop-mediated isothermal amplification.

Mycoplasma contamination in cell culture affects the properties of cell lines. Gold standard detection by microbiological culture takes days and requires specialists. The polymerase chain reaction and loop-mediated isothermal amplification (LAMP) are fast molecular options, but LAMP only requires one heating block for DNA amplification. This study presents a comparative genomic analysis of Mycoplasma species to identify common target genes different from the rrsA gene, which encodes 16 S rRNA. The aim is to implement a LAMP assay to detect Mycoplasma species, reducing the time and specialized equipment required for detection. We performed a comparative genomic analysis through Mauve software and the GView server and selected infB and clpB genes as target candidates for designing LAMP primers. We evaluated both genes by multiple sequence alignment (MSA). The infB gene presented the best score MSA assessment with lower odd-log values (5,480,281) than other genes. We selected the infB gene to design LAMP primers specific to Mycoplasma spp. We used these primers to implement LAMP at 63 °C for 30 min, which showed 100% positive amplifications for detecting Mycoplasma spp. In conclusion, we present a methodology utilizing the infB gene-based LAMP assay to detect three of the six most prevalent Mycoplasma species in cell culture.

Determination of tissue oxygen saturation by diffuse reflectance spectroscopy.

Significance: Tissue oxygenation is a parameter that allows for determining the health status of human beings. In diabetic patients, it is particularly important to evaluate this parameter as an indicator of microcirculatory problems in the extremities. Aim: We aim to obtain tissue oxygen saturation from diffuse reflectance measurements. Approach: A computational algorithm to automate the methodology was implemented with the aim of establishing a medical diagnosis technique that is non-invasive and easy to apply and requires a short evaluation time. Tissue oxygen saturation measurements were performed on a group of volunteers to whom a vascular occlusion was applied. It was observed that, by increasing the applied pressure to the arm of each volunteer, the tissue oxygen saturation progressively decreased. Results: The results indicate that the developed technique is an effective method for monitoring changes in blood hemodynamics in patients with some type of pathology in which tissue oxygenation is compromised. In addition, the expected behavior of tissue oxygen saturation during a vascular occlusion was obtained. Conclusions: A methodology to obtain tissue oxygen saturation from diffuse reflectance measurements was successfully developed. It meets the necessary characteristics to be considered a technique for obtaining StO2 because it can be applied in vivo and non-invasively and does not require a high computational cost; thus it is fast and capable of providing an objective and quantifiable evaluation.

Estudio sobre la salud mental de una población de niños y niñas escolarizados desde la perspectiva epidemiológica / Study on the mental health of a population of school children from an epidemiological perspective

Resumen Se presentan resultados de una investigación empírica sobre problemas comportamentales en niños y niñas escolarizados entre 6 y 11 años. El objetivo principal es describir, desde la perspectiva epidemiológica, los problemas comportamentales de una muestra clínica (N = 395; edad: . = 7.92 y DE = 1.75) y de una muestra no clínica (N = 363; edad: . = 8.78 años y DE = 1.73). Son objetivos específicos el analizar las diferencias por sexo y variables sociodemográficas en ambos contextos: clínico y no clínico. No se efectuó un estudio comparativo entre ambas muestras. Se administró el formulario Child Behaviour Checklist (CBCL) y una encuesta sociodemográfica a los adultos responsables. El análisis cuantitativo se efectuó mediante estudios de frecuencia, distribución y asociaciones entre variables con el objetivo de describir a ambas muestras desde el punto de vista de los resultados del CBCL y de las variables sociodemográficas. Se estudiaron asociaciones entre los valores de las escalas de síndromes del CBCL y las variables sociodemográficas mediante el análisis de la varianza (ANOVA). Se obtuvieron asociaciones estadísticamente significativas entre la presencia de problemas comportamentales y las condiciones socioeconómicas de la familia: a mayor vulnerabilidad socioeconómica y educativa, mayor deterioro en la salud mental infantil. Este estudio se encontró con la dificultad de las restricciones sanitarias por la pandemia de COVID-19 para continuar el trabajo de campo. Interesa replicar el estudio y considerar el impacto de la pandemia y el presunto deterioro de las variables sociodemográficas. Se debe priorizar la continuidad de una indagación sostenida para un seguimiento de la salud mental infantil.

Abstract This article shows the results of an empirical research study on behavioral and emotional problems in schoolchildren between 6 and 11 years old. From an epidemiological perspective the goal is to describe the behavioral problems of a clinical sample (N= 395, age: . = 7.92 y SD = 1.75) and a non-clinical sample (N = 363, age: M = 8.78 años y DE = 1.73). The specific objectives are to analyze the differences by sex and possible sociodemographic variables in both clinical and non-clinical contexts. A comparative study between both samples is not carried out. We administered the Child Behavior Checklist (CBCL) and a sociodemographic survey to the responsible adults. The quantitative analysis was carried out through studies of frequency, distribution and associations among variables in order to describe both samples from the point of view of the CBCL results and of the sociodemographic variables. In order to identify the possible sociodemographic conditioning factors in the childhood and youth psychopathology, we studied the associations among the CBCL syndrome scale scores and the different sociodemographic variables through the analysis of variance (ANOVA). The results of the clinical sample show mental health deterioration in boys and girls compared to previous studies. The increase of the internalizing and externalizing syndrome scores is significant. The prejudices and gender stereotypes constitute obstacles to gain access to mental health services in childhood, especially for girls whose psychological conditions may often go unnoticed. In the non-clinical sample, the gender distribution is even and the total average of average scores is lower compared to studies performed in other populations in previous years. In both samples we observe a significant relation between the psychological and behavioral problems and the socio-economic conditions of the family. The higher the educational and socio-economic vulnerability, the higher the deterioration of the children's mental health. The simultaneous study from the epidemiological perspective in both samples is necessary to detect psychopathological problems in childhood. This study encountered some limitations: the difficulty to continue the field work due to sanitary restrictions because of the COVID-19 pandemic. We want to replicate the study in both samples considering the impact of the pandemic and the alleged deterioration of the sociodemographic variables and family conditions. Another limitation has been the socio-economic homogeneity of the clinical sample. It would be useful in the future to include clinical samples that belong to other socioeconomic sectors who receive mental health care from private medical insurances or medical insurances run by labor unions. The shortage of epidemiological studies on emotional and behavioral problems in children and the lack of research work on the right to receive mental health care in childhood, indicate the absence of this topic in the political agenda. This deficit prevents the implementation of efficient programs to prevent and early detect mental health problems in children, to extend clinical care proposals in the community and to train professionals so that the programs can have an accurate impact on the population. It is a priority to continue the sustained inquiry in both populations in order to ensure the follow-up of the mental health conditions. Also, it would be useful to extend and deepen the analysis incorporating the examination of other family problems such as violence situations, consumption of psychoactive drugs, suicides and other loss situation.

A model-based head-to-head comparison of single-agent lurbinectedin in the pivotal ATLANTIS Study.

Introduction: Lurbinectedin is a selective inhibitor of oncogenic transcription U.S. Food and Drug Administration (FDA)-approved for patients with relapsed small cell lung cancer (SCLC) as monotherapy at 3.2 mg/m2 every 3 weeks (q3wk). ATLANTIS was a phase 3 study in SCLC with lurbinectedin 2.0 mg/m2 plus doxorubicin 40 mg/m2 q3wk vs physician's choice, with overall survival (OS) as the primary endpoint and objective response rate (ORR) as the secondary endpoint. This work aimed to dissect the contribution of lurbinectedin and doxorubicin to antitumor effects in SCLC, and to predict the efficacy of single-agent lurbinectedin at 3.2 mg/m2 in ATLANTIS to allow for a head-to-head comparison with the control arm. Methods: The dataset included exposure and efficacy data from 387 patients with relapsed SCLC (ATLANTIS, n=288; study B-005, n=99). Patients in the ATLANTIS control arm (n=289) were used for comparison. Unbound plasma lurbinectedin area under the concentration-time curve (AUCu) and total plasma doxorubicin area under the concentration-time curve (AUCDOX) were used as exposure metrics. Univariate and multivariate analyses were conducted to determine the best predictors and predictive model for OS and ORR. OS baseline hazard was best described by a log-logistic distribution, with chemotherapy-free interval (CTFI), lactate dehydrogenase, albumin, brain metastases, neutrophils/lymphocytes ratio, AUCu, and the interaction between AUCu and AUCDOX as predictors. Effect of AUCu on ORR best fitted to a sigmoid-maximal response (Emax) logistic model, where Emax was dependent on CTFI. Results: Head-to-head comparisons with predicted 3.2 mg/m2 lurbinectedin resulted in a positive outcome in ATLANTIS, with hazard ratio (95% prediction intervals [95% PI]) for OS of 0.54 (0.41, 0.72), and odds ratio (95% PI) for ORR of 0.35 (0.25, 0.5). Conclusion: These results support the superiority of lurbinectedin monotherapy for relapsed SCLC over other approved therapies.

Transudative Malignancy: Uncommon and Real.

Light's criteria are the cornerstone to differentiate exudates from transudates. The traditional literature states that malignant pleural effusions are rarely transudative; therefore, cytology tends to be low yield and not a cost-effective decision. This case describes an 82-year-old female who developed a transudative pleural effusion despite having an underlying malignancy, highlighting the importance of integrating clinical judgment into pursuing thoracentesis with the cytological examination.

Early Postoperative Outcomes of Lung Transplant Recipients With Abdominal Adverse Events.

INTRODUCTION: Patients undergoing lung transplantation (LT) are at high risk of developing serious abdominal complications, which can lead to higher rates of morbidity and mortality. The aim of this study was to investigate the incidence and spectrum of these complications when they develop during the first 30 days after LT, as well as their possible association with possible risk factors. METHODS: A retrospective study of 552 patients undergoing LT between 01/02/2006 and 06/03/2021 was carried out. A descriptive and analytical evaluation of the patients who experienced complications and those who did not was performed comparatively. Data related to patient characteristics and the lung transplantation procedure were collected. RESULTS: Overall, 8.2% of patients developed severe abdominal complications during the first 30 days; paralytic ileus was the most frequent (31.1%), closely followed by visceral perforation (26.7%). The percentage of patients who required an invasive procedure to manage post-transplant complications was 57.8%. Surgical intervention was required in 39.8%. The variables that showed a significant relationship with the development of severe short-term abdominal complications in the univariate analysis were the time of surgery, the use of ECMO/ ECC and red blood cell transfusion during or after surgery. In the multivariate study, however, only duration of surgery remained significant (p=0.03). CONCLUSION: The incidence of severe short-term abdominal complications after LT period was 8%. The commonest complications were paralytic ileus and intestinal perforation. Most patients did not require surgery. The only risk factor found associated with these complications was the duration of the surgical intervention.

COVID-19 vaccination rate and willingness of an additional dose among inflammatory bowel disease patients receiving biologic therapy: Fearless and with desire / Tasa de vacunación y aceptación de la dosis adicional de la vacuna frente al COVID-19 en los pacientes con enfermedad inflamatoria intestinal que reciben terapia biológica: sin miedo y con ganas

Background: Vaccination against COVID-19 prevents its severe forms and associated mortality and offers a promising action to control this pandemic. In September 2021, an additional dose of vaccine was approved in patients with immunosuppression including IBD patients on biologic agents. We evaluated the vaccination rate and additional dose willingness in this group of at risk patients. Methods: A single-center, cross-sectional study was performed among IBD patients on biologic agents and eligible for an additional dose of the COVID-19 vaccine. IBD clinical characteristics and type of vaccine and date of administration were checked in medical records. Acceptance was evaluated after telephone or face-to-face surveys in IBD patients. Results: Out of a total of 344 patients, 269 patients (46.1% male; mean age 47±16 years; Crohn's disease 73.6%) were included. Only 15 (5.6%) patients refused the COVID-19 vaccine mainly (40%) for conviction (COVID-19 pandemic denial). 33.3% would re-consider after discussing with their doctor and/or receiving information on the adverse effects of the vaccine. Previous to the additional dose, the COVID-19 vaccination was present in 94.4% of patients (n=254). Adverse effects occurred in 53.9% of the cases, mainly pain in the arm (40%). Up to 94.1% of the patients agreed to an additional dose and 79.4% had already received the additional dose at the final time of the assessment. Conclusions: IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. Physicians in charge of IBD units should provide information and confidence in the use of the vaccine in these IBD patients.(AU)

Antecedentes: La vacunación frente al COVID-19 constituye una acción prometedora para controlar esta pandemia. En septiembre de 2021, se aprobó una dosis adicional de vacuna en pacientes con inmunosupresión, incluidos los pacientes con enfermedad inflamatoria intestinal (EII) que reciben agentes biológicos. En este estudio se evaluó la tasa de vacunación y la disposición de recibir la dosis adicional de vacuna en este grupo de pacientes de riesgo. Métodos: Se realizó un estudio transversal unicéntrico con pacientes afectos de EII con tratamiento biológico y elegibles para una dosis adicional de la vacuna COVID-19. Se evaluó la aceptación y los efectos adversos de la vacuna mediante encuesta telefónica o presencial y se recopiló en las historias clínicas las características de la EII, el tipo de vacuna recibida y la fecha de administración. Resultados: De un total de 344 pacientes, 269 (46,1% varones; edad media 47±16 años; enfermedad de Crohn n=198) fueron incluidos. Solo 15 (5,6%) pacientes rechazaron la vacuna frente al COVID-19, el 40% por convicción (negación de la pandemia COVID-19). Antes de la dosis adicional, la vacuna COVID-19 se había administrado en el 94,4% de los pacientes (n=254). En el 53,9% de los casos presentaron efectos adversos, principalmente dolor en el brazo (40%). Hasta el 94,1% de los pacientes refería la aceptación de una dosis adicional de la vacuna y el 79,1% ya había recibido esta dosis adicional en el momento de la evaluación final. Conclusiones: Los pacientes con EII que reciben agentes biológicos aceptan la vacuna frente al COVID-19, así como una dosis adicional si se les recomienda. Los médicos responsables de las unidades de EII deben proporcionar información y confianza en el uso de la vacuna en estos pacientes.(AU)

Investigación en fisuras faciales: quo vadis España? / Investigation in facial fissures: quo vadis Spain?

Las fisuras orofaciales representan un grupo heterogéneo de malformaciones congénitas que afectan a distintas estructuras de la cavidad oral y de la cara. Globalmente, los bebés con estos trastornos presentan una mayor morbilidad y mortalidad a lo largo de su vida en comparación con individuos no afectados. Por ello, los avances en la investigación biomédica resultan ineludibles. Así, el objetivo general de este trabajo fue llevar a cabo una revisión bibliográfica para analizar narrativamente los 10 principales estudios primarios sobre fisuras orofaciales llevados a cabo en España, publicados del 2018 hasta la actualidad. Según esto, a nivel institucional, destaca la Universidad Complutense de Madrid (UCM) con cuatro artículos publicados por el grupo de investigación UCM 920202. También sobresale la Universidad Rey Juan Carlos de Madrid, con tres artículos relacionados con diferentes aspectos de la personalidad y la calidad de vida de los pacientes fisurados, así como otras muchas variables cognitivo-emocionales. En relación con la Universidad de Valencia, encontramos dos artículos llevados a cabo en amplias muestras de pacientes con fisuras. Por último, en Barcelona resulta destacable un estudio observacional sobre problemas otorrinolaringológicos en pacientes operados de fisura palatina. En conclusión, si bien en los últimos años se han publicado varios artículos sobre distintos aspectos relacionados con las fisuras, aún queda mucho trabajo por hacer. España debería seguir potenciando proyectos con líneas de trabajo centradas en estas alteraciones del desarrollo craneofacial. Se necesitan estudios amplios, multicéntricos y colaborativos, para ahondar en los mecanismos etiológicos y, en última instancia, en las posibles herramientas para su prevención. Del mismo modo, se necesitan ayudas para dilucidar mejor las cuestiones relacionadas con los tratamientos en todas las dimensiones de la salud, preferentemente a partir de ensayos clínicos controlados aleatorizados, que faciliten la traslación de conocimientos y su accesibilidad universal dentro del sistema sanitario público español.

SUMMARY: Orofacial clefts represent a heterogeneous group of congenital malformations affecting different structures of the oral cavity and face. Overall, infants with these disorders have a higher lifetime morbidity and mortality compared to unaffected individuals. Therefore, advances in biomedical research are unavoidable. Thus, the overall objective of this work was to conduct a literature review to narratively analyse the 10 main primary studies on orofacial clefts carried out in Spain, published from 2018 to date. According to this review, at an institutional level, the Complutense University of Madrid (UCM) is notable with 4 articles published by the UCM 920202 research group. The Rey Juan Carlos University of Madrid also stands out, with three papers related to different aspects of the personality and quality of life of cleft patients, as well as many other cognitive-emotional variables. In relation to the University of Valencia, we found two studies carried out on large samples of cleft patients. Finally, in Barcelona, an observational study on otorhinolaryngological problems in cleft palate patients is noteworthy. In conclusion, although several studies have been published in recent years on different aspects related to clefts, there is still much work to be done. Spain should craniofacial development. Large, multicenter and collaborative studies are needed to delve deeper into the aetiological mechanisms and, ultimately, into the possible tools for their prevention. Similarly, support is needed to better elucidate questions related to treatments in all dimensions of health, preferably randomised controlled clinical trials, which facilitate the transfer of knowledge and its universal accessibility within the Spanish public health system.

Cytogenetic and Molecular Characterization of Eigenmannia aff. desantanai (Gymnotiformes: Sternopygidae): A First Report of System of Sex Chromosomes ZW1W2/ZZ in Gymnotiformes.

Gymnotiformes a monophyletic group of fish endemic to the Neotropics, represent an important component of the freshwater ichthyofauna that presents relevant taxonomic problems. Thus, in view of the morphological complexity involving Eigenmannia (Gymnotiformes) fish species, this study aimed to characterize Eigenmannia aff. desantanai of the upper Paraguay River basin through cytogenetic and molecular analyses, to help in the correct identification and delimitation of species. This study reports a multiple sex system of the type ZW1W2/ZZ, with 2n = 31 for females and 2n = 30 for males. A single pair of chromosomes carrying the nucleolar organizing regions (NORs) was detected. The heterochromatin was colocated in NOR sites and mainly located in the centromeric regions of chromosomes. Besides that, individual sequences COI from the specimens of E. aff. desantanai were obtained, totalizing three haplotypes. The distance p between the haplotypes in E. aff. desantanai, ranged from 0.2% to 7.1%. Species delimitation tests indicated the existence of two possible operational taxonomic units of E. aff. desantanai. Thus, this study reports a new multiple sex system in Gymnotiformes and these specimens previously identified as E. aff. desantanai may belong to two distinct species.

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease.

Disruption of the lipid profile is commonly found in patients with inflammatory bowel disease (IBD). Lipoprotein lipase (LPL) is a key molecule involved in triglyceride metabolism that plays a significant role in the progression of atherosclerosis. In this study, our aim was to study whether serum LPL levels are different in IBD patients and controls and whether IBD features are related to LPL. This was a cross-sectional study that encompassed 405 individuals; 197 IBD patients with a median disease duration of 12 years and 208 age- and sex-matched controls. LPL levels and a complete lipid profile were assessed in all individuals. A multivariable analysis was performed to determine whether LPL serum levels were altered in IBD and to study their relationship with IBD characteristics. After the fully multivariable analysis, including cardiovascular risk factors and the changes in lipid profile that the disease causes itself, patients with IBD showed significantly higher levels of circulating LPL (beta coefficient 196 (95% confidence interval from 113 to 259) ng/mL, p < 0.001). LPL serum levels did not differ between Crohn's disease and ulcerative colitis. However, serum C-reactive protein levels, disease duration, and the presence of an ileocolonic Crohn's disease phenotype were found to be significantly and independently positively related to LPL. In contrast, LPL was not associated with subclinical carotid atherosclerosis. In conclusion, serum LPL levels were independently upregulated in patients with IBD. Inflammatory markers, disease duration and disease phenotype were responsible for this upregulation.

Non-hepatic Solid Organ Transplant in Patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series.

BACKGROUND AND AIMS: Solid organ transplantation, with the exception of liver, has rarely been reported in patients affected by inflammatory bowel diseases [IBD]. METHODS: This is an ECCO-CONFER project collecting cases of solid organ transplants [with the exclusion of liver] that were performed in IBD patients. We evaluated the change in the IBD therapy, need for bowel resection due to medically refractory IBD, or need for hospitalisation due to IBD relapse ['severe IBD course'] before and after transplantation. RESULTS: in total, 34 organ transplantations [28 kidney, five heart, one lung] in 33 IBD patients were collected [67% male, 55% Crohn's disease, mean age 53 ±â€…16 years]. The median follow-up was 4.3 years (interquartile range [IQR] 3.2-10.7); 29 patients [87.9%] were treated with tacrolimus, 25 [76%] with systemic steroids, 22 [67%] with mycophenolate mofetil, 11 [33%] with everolimus, six with cyclosporine [18%]. One patient was treated with infliximab, two patients with adalimumab, two patients with vedolizumab, one patient with ustekinumab. Overall, a severe IBD course was observed in three [9.3%] patients before transplantation and in four [11.7%] in the post-transplant setting [p = 0.26]. Three cases of cancer [excluding skin non-melanoma] [9.1%] were recorded in the post-transplantation period versus two in the pre-transplantation period [6.1%, p = 0.04]. Six patients [18.2%] died during the period of observation. No deaths were associated with IBD or complications of the transplant. CONCLUSIONS: In IBD patients, solid organ transplantation does not seem to impact on the IBD severity. However, the risk of malignancy needs further investigation.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Efficacy, Efficiency, and Acceptability of Telemedicine for Inflammatory Bowel Disease Patients' Follow-Up Care during the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, ambulatory clinic visits were replaced by the implementation of telehealth modalities in most inflammatory bowel disease (IBD) units. AIMS: The aim of this study was to assess the efficacy, efficiency, patient satisfaction, and acceptability of using telephone consultation in an IBD unit. METHODS: A prospective cohort study was performed in IBD patients who underwent telephone consultation during COVID-19 lockdown (between 16th March and 13th April 2020). To assess the efficacy of this telephone consultation (lockdown visit), nonscheduled visits, emergency consultation, hospital admission, and surgery from lockdown visit to the next scheduled consultation (post-lockdown) were checked. To evaluate efficiency, the time between lockdown visit and post-lockdown consultation was compared with previous consultation (pre-lockdown), and the total number of visits 12 months before and after lockdown visit was checked. A telephone survey was designed to rate perception for a telephone consultation. RESULTS: Out of a total of 274 patients, 220 patients (52.2% male; mean age 49 ± 16 years; Crohn's disease, n = 126; ulcerative colitis, n = 83; indeterminate colitis, n = 11) were included. Only one patient was consulted at the emergency department, 11 patients needed to rearrange the visit, and none patient underwent surgery before the scheduled post-lockdown visit. The interval to post-lockdown visit compared to pre-lockdown visit increased in 37.7% of patients. The satisfaction survey (n = 185) revealed that 94.6% perceived it was effective. However, 44.4% of patients rather prefer on-site consultation for follow-up. CONCLUSIONS: Telemedicine during the COVID-19 pandemic was shown to be effective and efficient to care for IBD patients. In addition, telephone consultation is well accepted by patients in non-extended follow-up periods.