In case of an emergency from upper airway obstruction, urgent insertion of primitive airway equipment, such as a small pharyngeal tube, was applied. Conclusions The main Hippocratic concepts on four still common acute and urgent respiratory diseases -pneumonia, pleurisy, thoracic empyema and upper airway obstruction- were identified and most of them were found to be in agreement with contemporary medical thinking and practice.Background Tolerogenic vaccines represent antigen-specific interventions designed to re-establish self-tolerance and thereby alleviate autoimmune diseases, which collectively comprise over 100 chronic inflammatory diseases afflicting more than 20 million Americans. Tolerogenic vaccines comprised of single-chain GM-CSF-neuroantigen (GMCSF-NAg) fusion proteins were shown in previous studies to prevent and reverse disease in multiple rodent models of experimental autoimmune encephalomyelitis (EAE) by a mechanism contingent upon the function of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs). GMCSF-NAg vaccines inhibited EAE in both quiescent and inflammatory environments in association with low-efficiency T cell receptor (TCR) signaling events that elicited clonal expansion of immunosuppressive Tregs. Methods This study focused on two vaccines, including GMCSF-MOG (myelin oligodendrocyte glycoprotein 35-55/MOG35-55) and GMCSF-NFM (neurofilament medium peptide 13-37/NFM13-37), that engaged the transgenic 2D2 TCR witase in CD44 expression in Tcon subsets. Subcutaneous administration of GMCSF-MOG without adjuvants inhibited EAE in wildtype mice, which had a replete Treg repertoire, but was pathogenic rather than tolerogenic in 2D2-FIG-Rag1-/- mice, which lacked pre-existing Tregs. Conclusions This study provided evidence that the GMCSF-MOG vaccine elicited antigenic responses beneath the CD40L triggering threshold, which defined an antigenic niche that drove dominant expansion of tolerogenic myelin-specific Tregs that inhibited EAE.Background Hypoxic-ischemic encephalopathy (HIE) is a life-threatening cerebrovascular disease. Neuroinflammation plays an important role in the pathogenesis of HIE, in which microglia are key cellular mediators in the regulation of neuroinflammatory processes. AdipoRon in vivo Colony-stimulating factor 1 (CSF1), a specific endogenous ligand of CSF1 receptor (CSF1R), is crucial in microglial growth, differentiation, and proliferation. Recent studies showed that the activation of CSF1R with CSF1 exerted anti-inflammatory effects in a variety of nervous system diseases. This study aimed to investigate the anti-inflammatory effects of recombinant human CSF1 (rh-CSF1) and the underlying mechanisms in a rat model of HIE. Methods A total of 202 10-day old Sprague Dawley rat pups were used. HI was induced by the right common carotid artery ligation with subsequent exposure of 2.5-h hypoxia. At 1 h and 24 h after HI induction, exogenous rh-CSF1 was administered intranasally. To explore the underlying mechanism, CSF1R inhibitor, BLZ94y rh-CSF1 attenuated neuroinflammation and improved neurological deficits after HI. The anti-inflammatory effects of rh-CSF1 partially acted through activating the CSF1R/PLCG2/PKCε/CREB signaling pathway after HI. These results suggest that rh-CSF1 may serve as a potential therapeutic approach to ameliorate injury in HIE patients.Background Bacterial bronchopneumonia (BP) is the leading cause of morbidity and mortality in cattle. The nasopharynx is generally accepted as the primary source of pathogenic bacteria that cause BP. However, it has recently been shown in humans that the oropharynx may act as the primary reservoir for pathogens that reach the lung. The objective was therefore to describe the bacterial microbiota present along the entire cattle respiratory tract to determine which upper respiratory tract (URT) niches may contribute the most to the composition of the lung microbiota. Methods Seventeen upper and lower respiratory tract locations were sampled from 15 healthy feedlot steer calves. Samples were collected using a combination of swabs, protected specimen brushes, and saline washes. DNA was extracted from each sample and the 16S rRNA gene (V3-V4) was sequenced. Community composition, alpha-diversity, and beta-diversity were compared among sampling locations. Results Microbiota composition differed across sampling locahe primary source of bacteria to the lung. This finding indicates that the nasopharynx is likely the most important location that should be targeted when doing bovine respiratory microbiota research. Video abstract.Background Bayesian adaptive methods are increasingly being used to design clinical trials and offer several advantages over traditional approaches. Decisions at analysis points are usually based on the posterior distribution of the treatment effect. However, there is some confusion as to whether control of type I error is required for Bayesian designs as this is a frequentist concept. Methods We discuss the arguments for and against adjusting for multiplicities in Bayesian trials with interim analyses. With two case studies we illustrate the effect of including interim analyses on type I/II error rates in Bayesian clinical trials where no adjustments for multiplicities are made. We propose several approaches to control type I error, and also alternative methods for decision-making in Bayesian clinical trials. Results In both case studies we demonstrated that the type I error was inflated in the Bayesian adaptive designs through incorporation of interim analyses that allowed early stopping for efficacy and wih, which is currently more accepted in the design and analysis of exploratory trials, then type I errors could be ignored and the designs could instead focus on the posterior probabilities of treatment effects of clinically-relevant values.Background Genetic research on longevity has provided important insights into the mechanism of aging and aging-related diseases. Pinpointing import genetic variants associated with aging could provide insights for aging research. Methods We performed a whole-genome sequencing in 19 centenarians to establish the genetic basis of human longevity. Results Using SKAT analysis, we found 41 significantly correlated genes in centenarians as compared to control genomes. Pathway enrichment analysis of these genes showed that immune-related pathways were enriched, suggesting that immune pathways might be critically involved in aging. HLA typing was next performed based on the whole-genome sequencing data obtained. We discovered that several HLA subtypes were significantly overrepresented. Conclusions Our study indicated a new mechanism of longevity, suggesting potential genetic variants for further study.