Impact of COVID-19 Infection on Pancreato-Biliary Diseases Requiring Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Viral infections are known to impact the pancreato-biliary system; however, there are limited data showing that the same is true of COVID-19. Endoscopic retrograde cholangiopancreatography (ERCP) can safely be performed in patients with COVID-19 infection, but outcomes of patients with COVID-19 infections and concomitant pancreatic and biliary disease requiring endoscopic intervention are unknown. AIMS: This study aims to evaluate the severity of pancreaticobiliary diseases and post-ERCP outcomes in COVID-19 patients. METHODS: Patients with pancreato-biliary disease that required inpatient ERCP from five centers in the United States and South America between January 1, 2020, and October 31, 2020 were included. A representative cohort of patients from each month were randomly selected from each site. Disease severity and post-ERCP outcomes were compared between COVID-19 positive and COVID-19 negative patients. RESULTS: A total of 175 patients were included: 95 COVID positive and 80 COVID negative. Mean CTSI score for the patients who had pancreatitis was higher in COVID-positive cohort by 3.2 points (p < .00001). The COVID-positive group had more cases with severe disease (n = 41) versus the COVID-negative group (n = 2) (p < .00001). Mortality was higher in the COVID-19 positive group (19%) compared to COVID-negative group (7.5%) even though the COVID-19-negative group had higher incidence of malignancy (n = 17, 21% vs n = 7, 7.3%) (p = 0.0455). CONCLUSIONS: This study shows that patients with COVID infection have more severe pancreato-biliary disease and worse post-ERCP outcomes, including longer length of stay and higher mortality rate. These are important considerations when planning for endoscopic intervention. CLINICALTRIALS: gov: (NCT05051358).

Remote pulmonary rehabilitation for interstitial lung disease: developing the model using experience-based codesign.

BACKGROUND: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study. METHODS: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops. RESULTS: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care. CONCLUSION: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention.

LIQUID NITROGEN SPRAY CRYOTHERAPY FOR ERADICATION OF DYSPLASTIC BARRETT'S ESOPHAGUS: RESULTS FROM A MULTICENTER PROSPECTIVE REGISTRY.

BACKGROUND AND AIMS: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma (IMC). Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS: Among 138 subjects, with LGD (24%), HGD (49%) and IMC (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after two years, and 67% and 92% after three years. In RFA-naive patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (adjusted hazard ratio [95% CI]:0.90 [0.83-0.96] per cm) and prior treatment with RFA (0.39 [0.22-0.69]) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n=6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort approximately 50% attained CEIM at 3 years.

Psychometric Evaluation of the School Climate and School Identification Measure-Student on Chilean Students: A Bifactor Model Approach.

School climate is a relevant construct for understanding social relations at school. The SCASIM-St has been widely defined as a multidimensional construct; however, new factor structures have not been explored through evidence that allows for interpreting school climate scores from an approach that respects the multidimensionality of the scale and, at the same time, allows for identifying the degree of essential unidimensionality in the data. Consequently, the objective was to analyze the psychometric properties of the SCASIM-St from a bifactor model approach, evaluating the influence of a general school climate factor versus five specific factors. The study involved 1860 students of both sexes (42% males and 58% females), with an average age of 16.63 years (SD = 0.664), from 17 secondary schools in Chile. The results obtained by a confirmatory factor analysis provided evidence that the best model was the bifactor model for the 38 items, with one general factor and five specific factors. The Explained Common Variance (ECV) values and reliability levels by hierarchical omega accounted for a strong general school climate factor with high levels of reliability. Evidence of external criterion validity, assessed through the attitude toward authority scale (AIA-A), showed a theoretically expected and significant relationship between the factors of both instruments. This study confirmed the psychometric robustness of the SCASIM-St scale by means of a bifactor model, allowing for a new, essentially unidimensional interpretation of the scale scores and providing an instrument to measure school climate in Chile.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope: A multicenter retrospective international study.

BACKGROUND: Duodenoscope-related multidrug-resistant organism (MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography (ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. METHODS: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score (1 to 10) on performance rating of the single-use duodenoscope, and adverse event (AE) rate. RESULTS: A total of 66 patients (26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47 (71.2%) grade 3 and 19 (28.8%) grade 4. The technical success rate was 98.5% (65/66). Procedural duration was 64 (interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66 (1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients (6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis (PEP), 1 cholangitis and 1 bleeding. CONCLUSIONS: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry.

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

A Randomized Controlled Phase 2 Dose-Finding Trial to Evaluate the Efficacy and Safety of Camostat in the Treatment of Painful Chronic Pancreatitis: The TACTIC Study.

BACKGROUND & AIMS: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP. METHODS: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety. RESULTS: A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%). CONCLUSION: We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies. CLINICALTRIALS: gov, Number: NCT02693093.

Hallazgo incidental de neoplasia primaria de pulmón: blastoma pulmonar en mujer adulta. Reporte de caso / Incidental finding of primary lung neoplasm: pulmonary blastoma in an adult woman, case report

El blastoma pulmonar es una neoplasia poco común y agresiva que se origina en el pulmón; está compuesto por tejido mesenquimal y epitelial inmaduro que imita la configuración pulmonar en etapas embrionarias. Tiene una baja incidencia y una alta tasa de mortalidad, con aproximadamente un 60 %. Este blastoma tiende a desarrollarse con mayor frecuencia entre la cuarta y quinta década de vida, siendo más prevalente en mujeres y generalmente asociado al tabaquismo. Se presenta el caso de una mujer de 23 años sin factores de riesgo conocidos, a quien se le diagnosticó incidentalmente un blastoma pulmonar primario. La paciente experimentaba dolor en la región costal izquierda, tos productiva, disnea y hemoptisis desde hace 30 días. Los hallazgos en las imágenes de rayos X y tomografías de tórax llevaron a la realización de una biopsia del pulmón izquierdo, que reveló fragmentos de tejido con una notable presencia de necrosis tumoral. Cinco días después, la paciente consultó nuevamente debido a un empeoramiento de los síntomas, incluyendo dolor torácico de tipo pleurítico. Se decidió realizar una lobectomía inferior izquierda, durante la cual se encontró un tumor sólido adherido a la pleura visceral, con masas tumorales en la pleura parietal. El estudio histopatológico final confirmó el diagnóstico de un tumor maligno de alto grado compatible con blastoma pulmonar. En conclusión, el blastoma pulmonar es una neoplasia rara que puede presentarse en diferentes etapas de la vida, aunque tiene mayor incidencia entre los 40 y 50 años. Es importante que los patólogos consideren esta enfermedad en sus diagnósticos diferenciales debido a los desafíos que implica su diagnóstico. Detectar el blastoma pulmonar en etapas tempranas es crucial para el tratamiento adecuado, aunque actualmente no se conocen marcadores predictivos confiables y el pronóstico de esta enfermedad es generalmente desfavorable.

Pulmonary blastoma is a rare and aggressive neoplasm that originates in the lung. It is composed of immature mesenchymal and epithelial tissue that mimics the embryonic configuration of the lung. It has a low incidence and a high mortality rate, of approximately 60%. Pulmonary blastoma tends to occur more frequently between the fourth and fifth decades of life, being more prevalent in women and generally associated with smoking. The case of a 23-year-old woman with no known risk factors is presented, who incidentally was diagnosed with a primary pulmonary blastoma. The patient experienced pain in the left costal region, productive cough, dyspnea, and hemoptysis for 30 days. Findings on X-ray and chest tomography led to a biopsy of the left lung, which revealed tissue fragments with significant tumor necrosis. Five days later, the patient consulted again due to worsened symptoms, including pleuritic chest pain. It was decided to perform a left lower lobectomy, during which a solid tumor attached to the visceral pleura with tumor masses in the parietal pleura was found. The final histopathological study confirmed the diagnosis of a high-grade malignant tumor compatible with pulmonary blastoma. In conclusion, pulmonary blastoma is a rare neoplasm that can occur at different stages of life, although it has a higher incidence between the ages of 40 and 50. Pathologists need to consider this disease in their differential diagnoses due to the challenges involved in its diagnosis. Detecting pulmonary blastoma at early stages is crucial for appropriate treatment, although currently there are no reliable predictive markers, and the prognosis of this disease is generally unfavorable.

Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years.

Background: Published reference equations for impulse oscillometry (IOS) usually encompass a specific age group but not the entire lifespan. This may lead to discordant predicted values when two or more non-coincident equations can be applied to the same person, or when a person moves from one equation to the next non-convergent equation as he or she gets older. Thus, our aim was to provide a single reference equation for each IOS variable that could be applied from infancy to old age. Methods: This was an ambispective cross-sectional study in healthy nonsmokers, most of whom lived in Mexico City, who underwent IOS according to international standards. A multivariate piecewise linear regression, also known as segmented regression, was used to obtain reference equations for each IOS variable. Results: In a population of 830 subjects (54.0% female) aged 2.7 to 90 years (54.8% children ≤12 years), segmented regression estimated two breakpoints for age in almost all IOS variables, except for R5-R20 in which only one breakpoint was detected. With this approach, multivariate regressions including sex, age, height and body mass index as independent variables were constructed, and coefficients for calculating predicted value, lower and upper limits of normal, percentage of predicted and z-score were obtained. Conclusions: Our study provides IOS reference equations that include the major determinants of lung function, i.e. sex, age, height and body mass index, that can be easily implemented for subjects of almost any age.

Psychometric properties of the Teachers' Sense of Efficacy Scale in a sample of Chilean public school teachers.

The Teachers' Sense of Efficacy Scale (TSES) has demonstrated suitable levels of reliability and validity for its use on the teacher population in several countries, and it is the most used scale to assess teachers' beliefs in their efficacy. However, few psychometric studies exist on its applicability to elementary teachers in public schools. This study analyzed the psychometric properties of the TSES in teachers who work in elementary education. The sample comprised 1,406 Chilean teachers, mainly women (77.2%), from various Chilean public and subsidized schools. The results obtained from three confirmatory factor analyses demonstrated that the model that best fit the data was bifactor exploratory structural equation modeling (B-ESEM) for 24 items, one general factor, and three residual factors. The results of the factorial invariance analysis indicate that the TSES remains stable up to the strict level of invariance for the variable sex. These results imply that the TSES can be used on Chilean teachers. The results are discussed based on the theoretical and empirical evidence available.

Competencias interculturales desde un enfoque ético intercultural en la formación inicial de profesionales en ciencias de la salud. un desafío ineludible

Chile es un país culturalmente diverso cuya población debe enfrentar dificultades relacionadas con la salud. Este ensayo tiene por objetivo reflexionar en torno a las competencias interculturales desde un enfoque ético intercultural, en la formación inicial de profesionales en ciencias de la salud. Se constata una salud carente y descontextualizada de la realidad cultural en la formación inicial en ciencias de la salud. Para evolucionar en esta área, se requiere imperiosamente formar a los profesionales en competencias interculturales desde un enfoque ético intercultural. Ello contribuirá al reconocimiento y comprensión de la otredad desde su propia cultura, a partir de la relación e intercambio de experiencias, conocimientos, saberes, entre otros. Para ello se requiere del diálogo intercultural entre profesionales y expertos pertenecientes a distintos sistemas de salud, con el fin de coconstruir desde la salud y enfermedad, para responder de forma oportuna y adecuada a las demandas de salud, y brindar un cuidado en salud digno y de calidad. En efecto, mitigará las desigualdades e injusticias, a la vez que proporcionará una vida más plena a las personas que conviven en una sociedad culturalmente diversa.

Chile is a culturally diverse country, and this population must face difficulties related to health. This essay aims to reflect on intercultural competencies from an intercultural ethical approach, in the initial training of professionals in health sciences. The initial training in health sciences shows that health is lacking and decontextualized from the cultural reality. In order to evolve in this area, it is imperative to train professionals in intercultural competencies from an intercultural ethical approach. This will contribute to the recognition and understanding of otherness from their own culture, based on the relationship and exchange of experiences, knowledge, wisdom, among others. This requires intercultural dialogue between professionals and experts belonging to different health systems, in order to co-construct from health and disease. This will allow a timely and adequate response to health demands. It will also provide quality and dignified health care and attention. In effect, it will mitigate inequalities and injustices, while providing a fuller life to people living in a culturally diverse society.

O Chile é um país culturalmente diverso, essa população deve enfrentar dificuldades relacionadas à saúde. Este ensaio tem como objetivo refletir sobre as competências interculturais a partir de uma abordagem ética intercultural, na formação inicial de profissionais em ciências da saúde. A saúde carente e descontextualizada da realidade cultural é verificada na formação inicial em ciências da saúde. Para evoluir nesta área, é imperativo formar profissionais em competências interculturais a partir de uma abordagem ética intercultural. Isso contribuirá para o reconhecimento e compreensão da alteridade a partir da própria cultura, do relacionamento e troca de experiências, saberes, saberes, entre outros. Para isso, é necessário o diálogo intercultural entre profissionais e especialistas pertencentes a diferentes sistemas de saúde; a fim de co-construir a partir da saúde e da doença. Isso permitirá uma resposta oportuna e adequada às demandas de saúde. Da mesma forma, prestará cuidados e atenção à saúde dignos e de qualidade. Com efeito, atenuará as desigualdades e as injustiças, ao mesmo tempo que proporcionará uma vida mais plena às pessoas que vivem numa sociedade culturalmente diversa.

Psychometric Validation of the Adult Prosocialness Behavior Scale in a Professional Teaching Context.

For the teaching profession, prosociality is a relevant skill. From this perspective, the present study aimed to examine the psychometric properties of the Adult Prosocialness Behavior Scale (APBS) in a professional setting of primary school Chilean teachers (n = 1404; mean age = 41.4; SD = 10.8; 77.4% women). ESEM and CFA were applied to evaluate its factor structure, internal consistency, factorial reliability, and invariance. The results supported a bifactor ESEM model in which prosociality was represented by a general latent factor and four specific factors (helping, sharing, caring, and empathy). A predominance of the unidimensional component of the APBS was observed (general factor, ECV = 0.938; ωh = 0.945), with adequate reliability (α = 0.932; ω of the factor general = 0.968) and invariance of the measurement in terms of gender. Its adequacy was confirmed by a good level of fit (RMSEA = 0.042 90%CI [0.036-0.049]; SRMR = 0.012; CFI = 0.995; TLI = 0.988). It is concluded that the APBS is a suitable instrument to measure prosociality in the professional setting studied. Its general and specific dimensions are relevant to the prosocial behaviors currently required of teachers. Future studies could contribute evidence of the transcultural validation of the APBS in other educational contexts in order to undertake comparative studies.

Psychometric Properties of the SV-RES60 Resilience Scale in a Sample of Chilean Elementary School Teachers.

The concept of resilience, identified as a crucial variable due to its association with several beneficial outcomes in adulthood, is of particular interest in the teaching field. Specifically, teachers work in a demanding, challenging, and stressful context that requires a remarkable ability to adapt; therefore, resilience is important in the field of teaching and training, as it plays a fundamental role in children's cognitive, social, and emotional development. This study sought to analyze the psychometric properties of the SV-RES60 Resilience Scale in a sample of Chilean elementary school teachers from first to eighth grade (N = 1406; mean age = 41.4; SD = 10.8). ESEM and bifactor ESEM analyses were performed to evaluate its factor structure, internal consistency, and reliability. The results supported a bifactor structure in which resilience was represented by one general latent factor and twelve specific factors (RMSEA = 0.032; 90%CI [0.030, 0.033]; SRMR = 0.012; CFI = 0.986; TLI = 0.977). A predominance of the unidimensional components of the SV-RES60 (general factor, ECV = 0.812; ωh = 0.975) and a high reliability (α = 0.981; ω of the general factor = 0.991) were observed. In conclusion, the SV-RES60 Resilience Scale is a suitable instrument for measuring the general factor of resilience in the investigated teaching environment. Future studies could contribute towards evidence of a reduced scale and transcultural validation to conduct comparative studies.

Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition.

BACKGROUND: The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. METHODS: SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD+-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. FINDINGS: LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. INTERPRETATION: Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. FUNDING: This work was supported by the Bill and Melinda Gates Foundation, the Sickkids Research Institute, the Canadian Institutes of Health Research, and the University Medical Center Groningen.

Vitamin D receptor and binding protein genes variants in patients with migraine.

BACKGROUND/OBJECTIVES: Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25-hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single-nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case-control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. METHODS: We genotyped 290 patients diagnosed with migraine and 300 age-matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. RESULTS: We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). CONCLUSIONS: In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies.

EUS-guided Gastroenterostomy: A Multicenter International Study Comparing Benign and Malignant Diseases.

BACKGROUND: Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for patients with gastric outlet obstruction without the risks of surgical bypass and the limited long-term efficacy of enteral self-expanding metal stent placement. However, due to its novelty, there is a lack of significant data comparing long-term outcomes of patients with EUS-GE, based on the underlying disease. In this study, we compare outcomes of EUS-GE on benign versus malignant indications. METHODS: Consecutive patients from 12 international, tertiary care centers who underwent EUS-GE over 3 years were extracted in a retrospective registry. Demographic characteristics, procedure-related information and follow-up data was collected. Primary outcome was the rate of adverse events associated with EUS-GE and the comparison of the rate of adverse events in benign versus malignant diseases. Secondary outcomes included technical and clinical success as well as hospitalization admission. RESULTS: A total of 103 patients were included: 72 malignant and 31 benign. The characteristics of the patients undergoing EUS-GE is shown in Table 1. The mean age of the cohort was 68 years and 58 years for malignant and benign etiology. Gender distribution was 57% and 39% being females in malignant and benign etiology group, respectively. Clinical success, technical success, average procedure time, and hospital length of stay were similar in both groups. Patients with benign underlying etiology had significantly higher number of surgically altered midgut anatomy (P=0.0379). CONCLUSION: EUS-GE is equally efficient regardless of the underlying etiology (malignant vs. benign), and the adverse events both groups were comparable.

Long-term outcomes of Zenker's peroral endoscopic myotomy (Z-POEM) for treatment of Zenker's diverticulum.

Background and study aims Z-POEM is now an established therapy for symptomatic Zenker's diverticulum (ZD). Short-term follow-up of up to 1-year post Z-POEM suggests excellent efficacy and safety; however, long-term outcomes are not known. Thus, we sought to report on longer-term outcomes (≥ 2 years) following Z-POEM for treatment of ZD. Patients and methods This was an International multicenter retrospective study at eight institutions across North America, Europe, and Asia over a 5-year period (from December 3, 2015 to March 13, 2020) of patients who underwent Z-POEM for management of ZD with a minimum 2-year follow-up. The primary outcome was clinical success, defined as improvement in dysphagia score to ≤ 1 without need for further procedures during the first 6 months. Secondary outcomes included rate of recurrence in patients initially meeting clinical success, rate of reintervention, and adverse events (AEs). Results A total of 89 patients (male 57.3 %, mean age 71 ±â€Š12 years) underwent Z-POEM for treatment of ZD (mean diverticulum size was 3.4 ±â€Š1.3 cm). Technical success was achieved in 97.8 % of patients (n = 87) with a mean procedure time of 43.8 ±â€Š19.2 minutes. The median post-procedure hospital stay was 1 day. There were eight AEs (9 %) (3 mild, 5 moderate). Overall, clinical success was achieved in 84 patients (94 %). Mean dysphagia, regurgitation, and respiratory scores all improved dramatically from 2.1 ±â€Š0.8, 2.8 ±â€Š1.3, and 1.8 ±â€Š1.6 pre-procedure to 0.13 ±â€Š0.5, 0.11 ±â€Š0.5, and 0.05 ±â€Š0.4, respectively, post-procedure at most recent follow-up (all P  < 0.0001). Recurrence occurred in six patients (6.7 %) during a mean length of follow-up of 37 months (range 24 to 63 months). Conclusions Z-POEM is a highly safe and effective treatment for Zenker's diverticulum with durable treatment effect to at least 2 years.

[Effect of resveratrol on cognitive functions in older adults: a systematic review and meta-analysis]. / Efecto del resveratrol sobre las funciones cognitivas en adultos mayores: una revisión sistemática y metaanálisis.

Introduction: Introduction: resveratrol has multiple beneficial effects on different body systems, including the central nervous system, however, the results reported on the effect on cognitive functions in older adults are inconsistent. Therefore, the purpose of this systematic review is to present a synthesis of knowledge about the effect of resveratrol on cognitive functions in older adults. Method: a systematic review was carried out according to the PRISMA-2009 criteria. The search for articles was carried out until September 7, 2021 in PubMed, Scopus, Web of Science, PsycINFO, SciELO, and TESIUNAM. The outcome variables were delayed, immediate, and working memory, and processing speed. The standardized mean difference (SMD) was estimated to assess the effect. Results: one thousand sixty-five studies were found, of which six met the eligibility criteria for the systematic review and meta-analysis. No significant effect was found on delayed memory (SMD = 0.69, 95 % CI: 0.85-2.23, p = 0.38), immediate memory (SMD = 0.56, 95 % CI: -0.20-1.31, p = 0.15), working memory (SMD = -0.21, 95 % CI: -0.74-0.32, p = 0.43) and processing speed (SMD = 0.25, 95 % CI: -0.58-1.07, p = 0.55). Conclusion: our results suggest that resveratrol does not have an effect on cognitive functions in older adults, however, it is necessary to carry out more studies with different doses, type of nutraceutical formulation and treatment time.

Introducción: Introducción: el resveratrol tiene múltiples efectos beneficiosos en diferentes sistemas del organismo, incluido el nervioso central, sin embargo, los resultados reportados sobre el efecto en las funciones cognitivas en adultos mayores son inconsistentes. Por lo anterior, el propósito de esta revisión sistemática es presentar una síntesis del conocimiento sobre los efectos del resveratrol en las funciones cognitivas en adultos mayores. Método: se llevó a cabo una revisión sistemática acorde con los criterios de PRISMA-2009. La búsqueda de artículos se realizó hasta el 7 de septiembre de 2021 en PubMed, Scopus, Web of Science, PsycINFO, SciELO y TESIUNAM. Las variables de desenlace fueron memoria diferida, inmediata y de trabajo y velocidad del procesamiento. Se estimó la diferencia de medias estandarizadas (DME) para evaluar el efecto. Resultados: se encontraron 1.065 estudios, de los cuales seis cumplieron los criterios de elegibilidad para la revisión sistemática y metaanálisis. No se encontró un efecto significativo en la memoria diferida (DME = 0,69, IC 95 %: 0,85-2,23, p = 0,38), memoria inmediata (DME = 0,56, IC 95 %: -0,20-1,31, p = 0,15), memoria de trabajo (DME = -0,21, IC 95 %: -0,74-0,32, p = 0,43) y velocidad de procesamiento (DME = 0,25, IC 95 %: -0,58-1,07, p = 0,55). Conclusión: nuestros resultados sugieren que el resveratrol no tiene un efecto sobre las funciones cognitivas en adultos mayores. No obstante, es necesario realizar más estudios con diferentes dosis, tipos de formulación del nutracéutico y tiempo de tratamiento.

A portable geometry-independent tomographic system for gamma-ray, a next generation of nuclear waste characterization.

One of the main activities of the nuclear industry is the characterisation of radioactive waste based on the detection of gamma radiation. Large volumes of radioactive waste are classified according to their average activity, but often the radioactivity exceeds the maximum allowed by regulators in specific parts of the bulk. In addition, the detection of the radiation is currently based on static detection systems where the geometry of the bulk is fixed and well known. Furthermore, these systems are not portable and depend on the transport of waste to the places where the detection systems are located. However, there are situations where the geometry varies and where moving waste is complex. This is especially true in compromised situations.We present a new model for nuclear waste management based on a portable and geometry-independent tomographic system for three-dimensional image reconstruction for gamma radiation detection. The system relies on a combination of a gamma radiation camera and a visible camera that allows to visualise radioactivity using augmented reality and artificial computer vision techniques. This novel tomographic system has the potential to be a disruptive innovation in the nuclear industry for nuclear waste management.