Dexamethasone weakens the respiratory effects of pro-inflammatory cytokine TNF-α in rat.

The goal of the current study was to identify the role of the glucocorticoids in the respiratory effects of proinflammatory cytokines. For this purpose intravenous injections of TNF-α were used in anesthetized spontaneously breathing rats before and after pretreatment of dexamethasone, a synthetic steroid with predominant glucocorticoid activity. Dexamethasone was injected intraperitoneally at a dose of 1 mg/kg. TNF-α was administrated into the tail vein at a dose of 40 mg/kg. We found that dexamethasone pretreatment eliminated the cytokine-induced increase in pulmonary ventilation and decrease in the hypoxic ventilatory response. Dexamethasone had a pronounced rapid effect on the respiratory activity of TNF-α as early as 30 minutes after administration. Therefore, we assume that this mechanism of action of dexamethasone was non-genomic, associated with the blocking of secondary mediators of the cytokine response.

Battle of the sections: Student outcomes and course feedback support combined prosection and dissection laboratory formats to maximize student success.

Gross anatomy laboratories frequently utilize dissection or prosection formats within medical curricula. Practical examination scores are consistent across the formats, yet these examinations assessed larger anatomical structures. In contrast, a single report noted improved scores when prosection was used in the hand and foot regions, areas that are more difficult to dissect. The incorporation of prosected donors within "Head and Neck" laboratories provided an opportunity to further characterize the impact of prosection in a structurally complex area. Retrospective analysis of 21 Head and Neck practical examination questions was completed to compare scores among cohorts that utilized dissection exclusively or incorporated prosection. Mean scores of practical examination questions were significantly higher in the prosection cohort (84.27% ± 12.69) as compared with the dissection cohort (75.59% ± 12.27) (p < 0.001). Of the 12 questions that performed better in the prosection cohort (88.42% ± 8.21), 10 items mapped to deeper anatomical regions. By comparison, eight of nine questions in the dissection cohort outperformed (88.44% ± 3.34) the prosection cohort (71.74% ± 18.11), and mapped to anatomically superficial regions. Despite the mean score increase with positional location of the questions, this effect was not statically significant across cohorts (p = 1.000), suggesting that structure accessibility in anatomically complex regions impacts performance. Student feedback cited structure preservation (71.5%) and time savings (55.8%) as advantages to prosection; however, dissection was the perceived superior and preferred laboratory format (88.6%). These data support combined prosection and dissection formats for improving student recognition of deeply positioned structures and maximizing student success.

Innovations Through Virtual Reality Simulation.

The need to augment standardized learner outcomes related to performance and clinical competency led to creating curricular elements that would provide instruction and assessment from multiple perspectives. The COVID-19 pandemic brought about needs for re-imagination of standardized simulated clinical experiences given the need for increased distance-learning and asynchronous formats. Our goal was to identify activities that would engage pre-clinical simulation through asynchronous virtual reality (VR) case scenarios. The intent was to provide additional resources whereby competencies could be more defined through performance metrics and standardized assessments additive to our established simulation-based curriculum throughout all curricular phases. Student reflection and metacognition identified gaps to guide future performance improvement through the VR activities. Learner outcomes encompassing history-taking, physical assessment, evidence-based clinical reasoning, and medical decision-making guided the instructional objectives. The composite data showed progressive improvements over five scenarios delivered in our second-year clinical medicine curriculum.

Cyclooxygenase and nitric oxide synthase pathways mediate the respiratory effects of TNF-α in rats.

TNF-α is the key inflammatory cytokine. TNF-α receptors are expressed in brain stem regions involved in respiratory control and also in the carotid bodies, which are the sensory organs monitoring arterial blood O2. We hypothesised that the circulating tumour necrosis factor (TNF)-α may affect the lung ventilation and modulate the hypoxic ventilatory response via activation of cyclooxygenase (COX) and nitric oxide synthase (NOS) pathways. The aim of the current study was to compare the respiratory effects of TNF-α before and after pretreatment with diclofenac or L-NG-nitro arginine methyl ester (L-NAME) nonspecific inhibitors of COX and NOS, respectively. The hypoxic ventilatory response was measured in anaesthetised rats using rebreathing techniques. We found that TNF-α increased the lung ventilation in normoxia but decreased the ventilatory response to hypoxia. Pretreatment with each of these inhibitors reduced respiratory effects of TNF-α. We believe that activation of COX and NOS-related pathways and also "cross-talk" between them mediates the TNF-α respiratory effects and underlies the impact of inflammation on the respiratory function.

Interleukin-1beta suppresses the ventilatory hypoxic response in rats via prostaglandin-dependent pathways.

We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1ß) on the ventilatory response to hypoxia. The goal was to test the hypothesis that IL-1ß impairs the hypoxic ventilatory response in vivo by indirectly inhibiting respiratory neurons in the brainstem via prostaglandins. Thus, IL-1ß was delivered by cerebroventricular injection, and the ventilatory hypoxic response was assessed in anesthetized, spontaneously breathing rats pretreated with or without diclofenac, a nonspecific inhibitor of prostaglandin synthesis. We found that the slope of the ventilatory response to hypoxia decreased almost 2-fold from 10.4 ± 3.02 to 4.06 ± 0.86 mL·min-1·(mm Hg)-1 (-61%) 90 min after administration of IL-1ß (p < 0.05). The slope of tidal volume and mean inspiratory flow also decreased from 0.074 ± 0.02 to 0.039 ± 0.01 mL·(mm Hg)-1 (-45%, p < 0.05), and from 0.36 ± 0.07 to 0.2 ± 0.04 mL·s-1·(mm Hg)-1 (-46%, p < 0.05), respectively. Pretreatment with diclofenac blocked these effects. Thus, the data indicate that IL-1ß degrades the ventilatory hypoxic response by stimulating production of prostaglandin. The increase of cerebral levels of IL-1ß, which is induced by the activation of immune cells in the brain, may impair respiratory chemoreflexes.