Articles: human.
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Acute respiratory distress syndrome (ARDS) is a widespread and often fatal clinical syndrome marked by the acute onset of pulmonary edema and inflammatory-mediated disruptions in alveolar-capillary permeability resulting in impaired gas exchange and tissue oxygenation with subsequent acute respiratory failure that accounts for 10.4% of all intensive care unit admissions worldwide and boasts a mortality rate of 38.5%. The current treatment for ARDS remains largely supportive. This is largely because of the many challenges of achieving a stable and sustainable animal model that recreates the pathophysiology of ARDS experimentally in a controlled setting to allow research to elucidate potential treatments of ARDS moving forward. ⋯ In conclusion, we demonstrated a viable animal model of human ARDS that is maintained for a prolonged period, suitable for continuous monitoring of the progression, and evaluation of potential future treatments and procedures to reduce patient morbidity and mortality. To carry out this two-hit model, lung injury was induced through a combination of bronchoalveolar lavage and oleic acid administration and the disease process of ARDS is subsequently tracked through clinically relevant parameters such as respiratory mechanics, cytokine response, aretrial blood gas (ABG) changes, and observation of postmortem histopathologic changes. This promising new model has the capacity to successfully replicate human ARDS which is a well-known and notoriously multifactorial pathogenic process to reproduce experimentally for an extended period of time. The "two-hit model" is a viable and appropriate model for the research of novel treatments for ARDS.
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The lancet oncology · Nov 2024
Review Practice GuidelineFertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: guidelines from ESGO, ESHRE, and ESGE.
The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.
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Anesthesia and analgesia · Nov 2024
Multicenter StudyContribution of Coordination Theories to the Determination of Human Factors Associated With Operating Room Perceived Performance.
The efficient and fluid organization of surgical interventions in an operating room (OR) and operating suite (OS) is important as these are among the most expensive units to run in medical-surgical facilities. The complexity of OS organization requires careful coordination, defined here as the directing of individuals' efforts toward achieving common and explicitly recognized goals. There is currently sparse literature on OS coordination, especially in the French context. This study aimed to respond to this gap by reporting on the coordination mechanisms associated with the perceived performance of OS across 4 facilities in an urban setting in France. ⋯ Based on existing literature on multi-team systems (as represented in the OS organization), this study identifies success factors influencing OS coordination. These include the OS manager's leadership skills; the identification of formal system objectives; and professional differentiation between stakeholders (absence/decrease of a sense of belonging to a multi-team system). This differentiation was related to the high degree of specialization within OS teams, each bringing different norms, cultures, and contingencies that induce dissonance in organization and task performance. Interventions targeting these success factors might improve coordination, and thus performance, in the OS.
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Splicing is a posttranscriptional RNA processing mechanism that enhances genomic complexity by creating multiple isoforms from the same gene. We aimed to characterize the isoforms expressed in the human peripheral nervous system, with the goal of creating a resource to identify novel isoforms of functionally relevant genes associated with somatosensation and nociception. We used long-read sequencing to document isoform expression in the human dorsal root ganglia from 3 organ donors and validated in silico by confirming expression in short-read sequencing from 3 independent organ donors. ⋯ This novel insertion is predicted to introduce a tyrosine phosphorylation site potentially phosphorylated by SRC. We also independently confirm a recently reported DRG-specific splicing event in WNK1 that gives insight into how painless peripheral neuropathy occurs when this gene is mutated. Our findings give a clear overview of mRNA isoform diversity in the human dorsal root ganglia obtained using long-read sequencing.
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Cannabidiol (CBD), the main nonpsychoactive cannabinoid of cannabis, holds promise for nonaddictive treatment of pain. Although preclinical studies have been encouraging, well-controlled human trials have been largely unsuccessful. To investigate this dichotomy and better understand the actions of CBD, we used high-content calcium imaging with automated liquid handling and observed broad inhibition of neuronal activation by a host of ionotropic and metabotropic receptors, including transient receptor potential (Trp) and purinergic receptors, as well as mediators of intracellular calcium cycling. ⋯ Taken together, these results demonstrate that CBD can reduce neuronal activity evoked by a strikingly wide range of stimuli implicated in pain signaling. The extensive effects underscore the need for further studies at substantially lower drug concentrations, which are more likely to reflect physiologically relevant mechanisms. The slow kinetics and block raise biophysical questions regarding the lipophilic properties of CBD and its action on channels and receptors within membranes.