Inhibition of Macrophage Functions by the C-Terminus of Murine S100A9 Is Dependent on B-1 Cells

The protein S100A9 plays a key role in the control of inflammatory response. the C-terminus of the murine S100A9 protein (mS100A9p) downregulates the spreading and phagocytic activity of adherent peritoneal cells. Murine peritoneal cells are constituted bymacrophages and B-1 cells, and the latter exert an inhibitory effect on macrophage functions by secreting interleukin-(IL-) 10. Here, we investigated the influence of B-1 cells on the inhibitory effect evoked by mS100A9p on macrophages. mS100A9p did not alter spreading and phagocytosis either by peritoneal macrophages obtained from mice deprived of B-1 cells or by bone marrow-derived macrophages (BMDM phi). Nevertheless, when BMDM phi were cocultivated by direct or indirect contact with B-1 cells treated with mS100A9p, the phagocytosis by BMDM phi was decreased, showing that the effect of mS100A9p on macrophages was modulated by B-1 cells and/or their secretory compounds. Furthermore, the inhibitory action of mS100A9p on phagocytosis by adherent peritoneal cells was abolished in cells obtained from IL-10 knockout mice. Taken together, the results show that mS100A9p has no direct inhibitory effect on macrophages; however, mS100A9p modulates B-1 cells, which in turn downregulates macrophages, at least in part, via IL-10. These data contribute to the characterization of S100A9 functions involving B-1 cells in the regulation of the inflammatory process.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao ButantanButantan Inst, Lab Pathophysiol, BR-05503000 São Paulo, BrazilHosp Sirio Libanes, Lab Neuromodulat & Expt Pain, BR-01308060 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Discipline Immunol, BR-04023900 São Paulo, BrazilCtr Univ Sao Camilo, Discipline Immunol, BR-04263200 São Paulo, BrazilUniv Paulista, Discipline Immunol, BR-04026002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Discipline Immunol, BR-04023900 São Paulo, BrazilFAPESP: FAPESP-2002/08277-7Web of Scienc

Implications of noncoding regulatory functions in the development of insulinomas

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations

Guía para la elaboración de trabajos científicos: grado, máster y postgrado

[ES]Esta Guía se ha realizado con el objetivo de ofrecer información relevante, concisa y precisa sobre los elementos y procedimientos básicos para la elaboración rigurosa y científica de los trabajos que hay que realizar en el Grado (Trabajo Fin de Grado) y en Post-Grado (Trabajo Fin de Máster y Tesis Doctoral)por parte de los discentes y/o profesionales de Ciencias de la Salud, Ciencias Sociales y afines. Toda la información introducida en esta Guía es fruto de la experiencia docente (cursos doctorado y formación continúa) e investigadora y tiene un marcado carácter práctico para que sirva de apoyo y facilite la realización, desarrollo y presentación de trabajos científicos universitarios y/o profesionales. En cada tema de esta guía se establecen los conocimientos, procedimientos y herramientas que se consideran imprescindibles y/o necesarios para la consecución de un buen trabajo científico, ya sea de Fin de Grado, Fin de Máster, Tesis Doctoral u Otros. Además, a lo largo de la misma se aportan consejos y recomendaciones prácticas que son consecuencia de la experiencia del equipo de docentes y expertos que han participado en la elaboración de esta Guía. La Guía nace con el doble propósito de aportar rigor y calidad en los trabajos científicos y ayudara los universitarios y profesionales a adquirir competencias y habilidades para presentar y reflejar de forma escrita los trabajos elaborados para conseguir el objetivo, graduación, máster, doctorado u otros. En la medida en que esta Guía sea útil al discente y a los profesionales en el proceso de aprendizaje de competencias y habilidades transversales y en su desarrollo profesional habremos conseguido nuestro objetivo

Relations between bedtime parenting behaviors and temperament across 14 cultures

ObjectivesThe present study examined parental sleep-supporting practices during toddlerhood in relation to temperament across 14 cultures. We hypothesized that passive sleep-supporting techniques (e.g., talking, cuddling), but not active techniques (e.g., walking, doing an activity together), would be associated with less challenging temperament profiles: higher Surgency (SUR) and Effortful Control (EC) and lower Negative Emotionality (NE), with fine-grained dimensions exhibiting relationships consistent with their overarching factors (e.g., parallel passive sleep-supporting approach effects for dimensions of NE). MethodsCaregivers (N = 841) across 14 cultures (M = 61 families per site) reported toddler (between 17 and 40 months of age; 52% male) temperament and sleep-supporting activities. Utilizing linear multilevel regression models and group-mean centering procedures, we assessed the role of between- and within-cultural variance in sleep-supporting practices in relation to temperament. ResultsBoth within-and between-culture differences in passive sleep-supporting techniques were associated with temperament attributes, (e.g., lower NE at the between-culture level; higher within-culture EC). For active techniques only within-culture effects were significant (e.g., demonstrating a positive association with NE). Adding sleep-supporting behaviors to the regression models accounted for significantly more between-culture temperament variance than child age and gender alone. ConclusionHypotheses were largely supported. Findings suggest parental sleep practices could be potential targets for interventions to mitigate risk posed by challenging temperament profiles (e.g., reducing active techniques that are associated with greater distress proneness and NE).Peer reviewe

Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promote Disease Progression and Induce the Production of Different Cytokines in Macrophages and B-1 Cells

The extracellular vesicles (EVs) released by Leishmania can contribute to the establishment of infection and host immunomodulation. In this study, we characterized the shedding of EVs from Leishmania (Leishmania) amazonensis promastigotes. This species is the causative agent of cutaneous leishmaniasis, and its role during interactions with bone marrow-derived macrophages (BMDMs) and peritoneal B-1 cells was evaluated. Leishmania amazonensis promastigotes cultivated in vitro at different times and temperatures spontaneously released EVs. EVs were purified using size-exclusion chromatography (SEC) and quantitated by nanoparticle tracking analysis (NTA). NTA revealed that the average size of the EVs was approximately 180 nm, with concentrations ranging from 1.8 × 108 to 2.4 × 109 vesicles/mL. In addition, the presence of LPG and GP63 were detected in EVs obtained at different temperatures. Naïve BMDMs stimulated with EVs exhibited increased IL-10 and IL-6 expression. However, incubating B-1 cells with parasite EVs did not stimulate IL-10 expression but led to an increase in the expression of IL-6 and TNFα. After 7 weeks post-infection, animals infected with L. amazonensis promastigotes in the presence of parasite EVs had significant higher parasite load and a polarization to Th2 response, as compared to the group infected with the parasite alone. This work demonstrated that EVs isolated from L. amazonensis promastigotes were able to stimulate macrophages and B-1 cells to express different types of cytokines. Moreover, the immunomodulatory properties of EVs probably contributed to an increase in parasite burden in mice. These findings suggest that the functionality of L. amazonensis EVs on immune system favor of parasite survival and disease progression

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activityS

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

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

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI