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- Martínez-Sánchez, Noelia, et al.
(författare)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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- Venero, J. L., et al.
(författare)
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ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
- 2023
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Ingår i: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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- Arribas, Christina, et al.
(författare)
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Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools : impact of the sociodemographic index (SDI)
- 2024
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447.
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress.Methods: This was a global, prospective, cross-sectional study. A survey was distributed May–November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location.Results: The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others.Conclusions: Socio-economic status of countries impacts on neonatal analgosedation management.
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- Gilbert, R. E., et al.
(författare)
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Trends in child maltreatment reply
- 2012
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Ingår i: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9831, s. 2049-2049
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Tidskriftsartikel (refereegranskat)
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- Batchelor, Timothy J. P., et al.
(författare)
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Guidelines for enhanced recovery after lung surgery : recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS)
- 2019
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Springer. - 1010-7940 .- 1873-734X. ; 55:1, s. 91-115
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Forskningsöversikt (refereegranskat)abstract
- Enhanced recovery after surgery is well established in specialties such as colorectal surgery. It is achieved through the introduction of multiple evidence-based perioperative measures that aim to diminish postoperative organ dysfunction while facilitating recovery. This review aims to present consensus recommendations for the optimal perioperative management of patients undergoing thoracic surgery (principally lung resection). A systematic review of meta-analyses, randomized controlled trials, large non-randomized studies and reviews was conducted for each protocol element. Smaller prospective and retrospective cohort studies were considered only when higher-level evidence was unavailable. The quality of the evidence base was graded by the authors and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery after Surgery Society and the European Society for Thoracic Surgery. Recommendations were developed for a total of 45 enhanced recovery items covering topics related to preadmission, admission, intraoperative care and postoperative care. Most are based on good-quality studies. In some instances, good-quality data were not available, and subsequent recommendations are generic or based on data extrapolated from other specialties. In other cases, no recommendation can currently be made because either equipoise exists or there is a lack of available evidence. Recommendations are based not only on the quality of the evidence but also on the balance between desirable and undesirable effects. Key recommendations include preoperative counselling, nutritional screening, smoking cessation, prehabilitation for high-risk patients, avoidance of fasting, carbohydrate loading, avoidance of preoperative sedatives, venous thromboembolism prophylaxis, prevention of hypothermia, short-acting anaesthetics to facilitate early emergence, regional anaesthesia, nausea and vomiting control, opioid-sparing analgesia, euvolemic fluid management, minimally invasive surgery, early chest drain removal, avoidance of urinary catheters and early mobilization after surgery. These guidelines outline recommendations for the perioperative management of patients undergoing lung surgery based on the best available evidence. As the recommendation grade for most of the elements is strong, the use of a systematic perioperative care pathway has the potential to improve outcomes after surgery.
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- Consiglio, Camila, et al.
(författare)
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Immune system adaptation during gender-affirming testosterone treatment
- 2023
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
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