Beta-cell mass adaptation to ileum nutrient flow. An experimental model

The population with obesity has increased at an alarming rate during this century. Bariatric surgery has been demonstrated to be a good method to control weight and, most importantly, associated comorbidities, such as type 2 diabetes mellitus or high blood pressure. The reason why this happens even before losing significant weight remains unclear. Many authors believe that incretins play a main role, triggering special functions of the digestive tract. In reports, these hypotheses are known as foregut and hindgut theories. Initially, the theories were mutually exclusive; additionally, many other propositions have been analysed, according to different surgical techniques (e.g., bile acids and specific enterohormonal components). To elucidate the participation of the ileum, we developed a surgical technique to study the rapid response to nutrients in the ileum. Our goal was to study the stress functional test and histological changes in the pancreas that may explain the variations in glycaemic homeostasis in our rat model. After the oral glucose tolerance test, the experimental group presented an increased insulin release response with conserved glycaemia. We report an increasing beta-cell mass in the experimental group (+11.87 mg vs. +9.65 mg, respectively), while alpha-cell mass was not different. Based on transcription factors, the pathways that were increased were the proliferation process (as the number of PCNA-positive cells in the experimental group versus sham (+12.06 vs. +6.2 PCNA+ cells/mm2)) and transdifferentiation (ARX; +2.67 ARX+ cells/mm2 in the experimental group vs. +2.04 ARX+ cells/mm2 in the controls). We report the consequences of the rapid arrival of nonprocessed nutrients to the ileum on the endocrine cellular pancreas. The ileum could be a principal effector in the enterohormonal axis, which conditions endocrine pancreas cellularit

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Una nueva técnica quirúrgica focalizada en el estudio del íleon: la transposición preduodenal del íleon

Aims: Our main goal is to study the effects on the carbohydrate metabolism. Thus, we designed various experimental surgical models on healthy non-obese Wistar rats to reproduce several conditions. In this sense, we report a new experimental model. It is well known that bariatric surgery has important effects on the control of Type 2 Diabetes Mellitus. The underlying reasons are yet unknown, although the different theories focused in the release of different hormones after the pass of the nutrients through the tract. These released hormones have opposite effects that come together in a balanced glycemic metabolism. Materials and methods: After bariatric surgical techniques, the modified anatomy resulted in an imbalance of the secreted hormones. Wistar rats were randomized in two groups Sham and surgical group. Our model consisted on the transposition of the terminal ileum right after the pylorus. Weight gain, food intake, and basal glycemia were measured weekly. Results: We did not obtain significant differences between both groups for these functional variables. Conclusions: This technique involved an early pass of the bolus through the ileum. The change on the luminal pH, along with the lack of enzymes to absorb the content, or the changes in the release of several hormones must be variables to the study. The mortality rate was assumable considering it was an experimental model on animals.Objetivo: Crear un nuevo modelo quirúrgico experimental en ratas Wistar sanas no obesas para estudiar los efectos del metabolismo glucídico. Es bien sabido que las técnicas de cirugía bariátrica tienen un efecto importante sobre la resolución de la diabetes mellitus tipo 2. Se han invocado diferentes hipótesis, algunas centradas en el papel que tienen distintas hormonas secretadas por el propio tubo digestivo tras el paso de los nutrientes a su través, pero las razones últimas subyacentes permanecen desconocidas. El efecto contrapuesto de dichas hormonas consigue un efecto de control glucémico. El desequilibrio hormonal tras las alteraciones anatómicas de las cirugías bariátricas podría estar en la base de dicha mejora del metabolismo glucídico final. Material y métodos: Las ratas fueron operadas en dos grupos (control quirúrgico y experimental) y se procedió a disponerles el íleon anastomosado al antro pilórico, previo al esfínter pilórico. Medimos distintos parámetros funcionales (ganancia de peso, ingesta y glucemias semanales). Resultados: No obtuvimos diferencias significativas en la evolución de estos parámetros. Conclusiones: Este modelo será útil para nuestro propósito de estudiar el íleon, en su componente secretor de enterohormonas, cuando el paso de los nutrientes se produzca tempranamente. La mortalidad fue asumible, dada la innovación técnica realizada

The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats.

Roux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear. We reproduced the RYGB technique in Wistar and Goto-Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum. At least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine

Body painting as a useful technique in teaching anatomy for sciences of physical activity and sports students

Anatomical knowledge supports any approach to the knowledge on physical activities and sport activities. The present report is focused in a technic to improve the learning of surface anatomy through the body painting. We had considered many ways in which human anatomy could be taught in an updated way to sciences of physical activity and sport students. All strategies and didactic resources must optimize the overall the teaching processes. We tested several methodological techniques in anatomy teaching to several students. For this purpose, we used a route of practical session, where students painted their own bodies. For one semester, the first-year sport sciences students, enrolled in the Human Anatomy signature at the University of Cádiz participated in this study. To complete the teaching activity, students were divided into 2 groups with 40 students each. At the end of the course, the students were asked to complete a satisfaction questionnaire supplied to them such through an on-line platform. We included this activity in other anatomical students, as medical student, and we modified this experience according to the specific studies. No similar experiences were reported in these university students. On the basis of the results, we recommend the body painting activity as a useful tool for learning human anatom

Bariatric surgery influences β-Cell turnover in non obese rats

Background. The aim of this study was to investigate the relation between the different bariatric surgeries and pancreatic β-cell turnover. Material and Methods. We used healthy adult male Wistar rats to undergo the different techniques. Three surgical techniques were developed (malabsorptive, Sleeve gastrectomy and Roux-Y Gastric Bypass-), together with two control groups (Sham and fasting control). Pancreatic β-cell mass was measured, as well as apoptosis, proliferation and neogenesis related to cellular turnover. Otherwise, we measured the functional issues to elucidate the physiological role that these surgical techniques trigger in the carbohydrate metabolism (e.g. food intake, weight gain, intraperitoneal glucose tolerance test, and basal glycaemia). Results included the differences in phenotypes of the rat after the surgery. The rats did not show important differences in glycaemic parameters between the surgical groups. The β-cell mass presented modifications related with proliferation processes. A significant increase of β-cell mass in the malabsorptive technique was reported. On the other hand, the peripheral resistance to insulin tended to be reduced in rats which underwent malabsorptive and mixed techniques. Conclusion. This work showed an increase in β-cell mass after the resection of an important portion of small bowel. The Roux-Y Gastric Bypass produced a non-significant increase in β-cell mass. We considered that these implications of surgery over the endocrine pancreas must be one of the mechanisms related to the improvement of type 2 Diabetes mellitus following bariatric surgery