El desafío de ampliar las camas de la UCI durante la pandemia de COVID-19 : una descripción general del servicio de enfermería de cuidados intensivos

Objetivo: Relatar a organização e o planejamento das frentes de trabalho junto à gestão do Serviço de Enfermagem e Medicina de um Centro de Terapia Intensiva (CTI) para a abertura dos novos leitos críticos. Método: Relato de experiência de enfermeiros do CTI, ocorrido no período de março a agosto de 2020. Para propor uma reflexão crítica, a experiência foi relatada com base nas ações de prática avançada em enfermagem. Resultados: Na pesquisa: grupos multidisciplinares foram criados para revisão e elaboração de fluxos e protocolos com base na prática baseada em evidências e readaptações às rotinas. Na educação: foram realizados treinamentos in locodas práticas assistenciais adotadas. As temáticas mais emergentes foram paramentação/desparamentação, manobra de prona, hemodiálise e oxigenação por membrana extracorpórea. Devido àcontratação imediata de profissionais foram elaborados treinamentos presenciais e à distância e simulações realísticas. Quanto àprática assistencial: foram elaborados novos protocolos e fluxos de atendimento. Quanto à gestão:as unidades foram alocadas no anexo ao prédio principal, sendo abertos clustersde até 10 leitos, totalizando 105 leitos. A equipe foi redimensionada, grupos foram reestruturados, alocando enfermeiros e técnicos de enfermagem experientes em unidades novaspara treinamento dos admitidos e segurança dos pacientes.RealizadosHuddlesdiários para mapeamento de riscos ocupacionais e assistenciais. Conclusão: O relato de experiência pode propiciar aos enfermeiros diversas reflexões acerca da situação vivenciada nos CTIs dianteda pandemia da COVID-19 e a certeza de um processo inacabado que ainda necessita de adaptações, pois o cenário da pandemia permanece desconhecido e imprevisível.Objective: Report the organization of the work fronts with the management of the Nursing and Medicine Service of the Intensive Care Center (ICU) for the organization, planning and opening of new critical beds. Method: This is an experience report of ICU nurses, from March to August 2020. To propose a critical reflection of the work process, it will be based on the actions of advanced nursing practice (APS). Results: In the research: multidisciplinary groups were created to review and develop flows and protocols based on evidence-based practice and readaptations to routines. Nurses integrated each group according to their expertise. In education: training was carried out in loco on the adopted care practices. The most emerging themes were attire/dedressing, prone maneuver, hemodialysis and extracorporeal membrane oxygenation (ECMO). Due to the immediate hiring of professionals, face-to-face and distance learning training was prepared. Also, realistic simulations took place. As for care practice: new protocols and care flows were developed. As for management: the units were allocated in the annex to the main building, with clusters of up to 10 beds being opened, totaling 105 beds. The team was resized, groups were restructured, allocating experienced nurses and nursing technicians in new units for training admissions and patient safety. Daily Huddles were carried out to map occupational and care risks. Conclusion: Through the critical-reflective process and planning, new strategies were essential. In order to redesign our purpose, there was a need for constant adaptations, as the pandemic scenario remains unpredictable.Objetivo: Informar la organización de los frentes de trabajo con la dirección del Servicio de Enfermería y Medicina del Centro de Cuidados Intensivos (UCI) para la organización, planificación y apertura de nuevas camas críticas. Método: Se trata de un relato de experiencia de enfermeras de UCI, de marzo a agosto de 2020. Para proponer una reflexión crítica del proceso de trabajo, se basará en las acciones de la práctica avanzada de enfermería (APS). Resultados: En la investigación: se crearon grupos multidisciplinarios para revisar y desarrollar flujos y protocolos basados en la práctica basada en la evidencia y readaptaciones a las rutinas. Las enfermeras integraron cada grupo de acuerdo con su experiencia. En educación: se realizó capacitación in loco sobre las prácticas de cuidado adoptado. Los temas más emergentes fueron vestimenta / desvestirse, maniobra en decúbito prono, hemodiálisis y oxigenación por membrana extracorpórea (ECMO). Debido a la contratación inmediata de profesionales, se preparó la formación presencial y a distancia. Además, se llevaron a cabosimulaciones realistas. En cuanto a la práctica asistencial: se desarrollaron nuevos protocolos y flujos asistenciales. En cuanto a la gestión: las unidades se ubicaron en el anexo del edificio principal, con la apertura de grupos de hasta 10 camas, totalizando 105 camas. Se redimensionó el equipo, se reestructuraron los grupos, asignando enfermeros experimentados y técnicos de enfermería en nuevas unidades para la formación de admisiones y seguridad del paciente. Se llevaron a cabo reuniones diarias para mapear los riesgos ocupacionales y de atención. Conclusión: A través del proceso crítico-reflexivo yla planificación, las nuevas estrategias fueron fundamentales. Para rediseñar nuestro propósito, era necesario realizar adaptaciones constantes, ya que el escenario de la pandemia sigue siendo impredecible

HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling

Aims/hypothesis Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.MethodsHuman white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2AdipoqCre) and performed a large panel of metabolic tests.Results We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.Conclusions/interpretation In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.Data availability Array data have been submitted to the GEO database at NCBI (GSE148699).</p

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Regulation of TNF-alpha, IL-1 and IL-6 synthesis in differentiating human monoblastoid leukemic U937 cells

The human monoblastoid tumor cell line U937 was induced to differentiate along the monocyte/macrophage lineage by treatment with 5 x 10(-9) M 12-O-tetradecanoyl phorbol-13-acetate (TPA). Between 2 h and 4 h following TPA-treatment U937 cells started to release significant amounts of TNF-alpha which remained detectable until 8-10 days. A significant IL-1 beta release was measured 24 h-48 h post stimulation and increased levels of IL-1 beta persisted until 20-22 days of culture. In contrast no release of either IL-1 alpha or IL-6 could be detected with 5 x 10(-9) M TPA during the whole time course of the experiments. The sequential induction of TNF-alpha and IL-1 beta appeared to be independently regulated since TNF-alpha release was not required for the onset of IL-1 beta production. Northern-blot analysis confirmed the sequential induction and the long term expression of TNF-alpha and IL-1 beta mRNAs. Western-blot analysis predominantly showed a high molecular weight IL-1 beta protein of about 35 kD. Further investigations on the regulation of cytokine production and release by TPA-differentiated U937 cells revealed that TNF-alpha and IL-1 beta synthesis was not influenced by exogenously added rhTNF-alpha or PGE2, whereas rh gamma-IFN specifically enhanced the IL-1 beta production. Thus, the regulation and intracellular processing of cytokines generated by differentiating U937 cells shows some differences when compared to mature monocytes/macrophages which may be related to the tumorigenic origin of U937 cells or to an incomplete differentiation

The human mirror neuron system : a common neural basis for social cognition?

According to the theory of embodied simulation, mirror neurons (MN) in our brain's motor system are the neuronal basis of all social-cognitive processes. The assumption of such a mirroring process in humans could be supported by results showing that within one person the same region is involved in different social cognition tasks. We conducted an fMRI-study with 75 healthy participants who completed three tasks: imitation, empathy, and theory of mind. We analyzed the data using group conjunction analyses and individual shared voxel counts. Across tasks, across and within participants, we find common activation in inferior frontal gyrus, inferior parietal cortex, fusiform gyrus, posterior superior temporal sulcus, and amygdala. Our results provide evidence for a shared neural basis for different social-cognitive processes, indicating that interpersonal understanding might occur by embodied simulation.publishe

Effective Connectivity of the Human Mirror Neuron System During Social Cognition

The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy, and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL), and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying different connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection, and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory-loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.publishe