Emergency department utilization in elderly patients: a report from the National Emergency Department Information System (NEDIS) of Korea, 2018-2022

Objective With general aging of the population, emergency department (ED) utilization by elderly patients is increasing. In this study, we analyzed data on ED visits of patients aged 65 years and older in Korea. Methods The study is a retrospective analysis of National Emergency Department Information System (NEDIS) data from 2018–2022, focusing on patients aged 65 years and older who visited EDs across Korea. ED utilization data were analyzed using Korean Triage and Acuity Scale (KTAS) scores. The patients were divided into three age groups, and common chief complaints and diagnoses were identified. Age- and sex-standardized ED visits per 100,000 population and outcomes were also analyzed. Results During the study period, there was a total of 9,803,065 elderly patient ED visits. The mean patient age was 76.4±7.6 years, and 47.6% were men. The ED mortality rate and in-hospital mortality rate were 1.8% and 4.6%, respectively. The KTAS scores 1–2 group accounted for 11.0% of patients, KTAS score 3 group for 42.5%, KTAS scores 4–5 group for 37.2%, and KTAS score unknown group for 9.4%. When patients were categorized into three age groups, the oldest group exhibited the highest rates of KTAS score 1, severe illness diagnoses, and mortality. The most frequently reported chief complaint was abdominal pain, and the most common diagnosis was light headedness. When analyzing the data by year, the COVID-19 outbreak had a discernible impact on ED visits and clinical outcomes. Conclusion Over the past 5 years, ED visits for elderly patients have averaged 26,050 per 100,000 population per year, with a temporary decline during the COVID-19 pandemic and a subsequent upward trend

Efficacy and safety of rapid intermittent bolus compared with slow continuous infusion in patients with severe hypernatremia (SALSA II trial): a study protocol for a randomized controlled trial

Background Hypernatremia is a common electrolyte disorder in children and elderly people and has high short-term mortality. However, no high-quality studies have examined the correction rate of hypernatremia and the amount of fluid required for correction. Therefore, in this study, we will compare the efficacy and safety of rapid intermittent bolus (RIB) and slow continuous infusion (SCI) of electrolyte-free solution in hypernatremia treatment. Methods This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental groups. A total of 166 participants with severe hypernatremia will be enrolled and divided into two randomized groups; both the RIB and SCI groups will be managed with electrolyte-free water. We plan to infuse the same amount of fluid to both groups, for 1 hour in the RIB group and continuously in the SCI group. The primary outcome is a rapid decrease in serum sodium levels within 24 hours. The secondary outcomes will further compare the efficacy and safety of the two treatment protocols. Conclusion This is the first randomized controlled trial to evaluate the efficacy and safety of RIB correction compared with SCI in adult patients with severe hypernatremia

Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia

Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia colt (E coli, 5.0 * 10<^>9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-alpha, interleukin [IL]-1 beta, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTRE-M1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E coil, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum beta-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2 similar to 4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

The identification of immune responses required for durable control of childhood acute lymphoblastic leukemia

Remarkable clinical successes have been achieved with targeted immunotherapies directed at a surface antigen of leukemia blasts in patients with relapse or chemotherapy-refractory B-ALL. This single antigen-targeted approach, however, is highly prone to tumor immune escape. Development of resistance to therapy, commonly caused by the emergence of target-negative escape variants, remains a major drawback of CD19-directed therapies for B-ALL. The efficacy of strategies that direct T cell-mediated cytotoxicity towards leukemic cells bearing non-immunogenic antigens is limited, with a lack of evidence that these interventions establish immunological memory. In this study, I use the Eμ-ret mouse model to better understand the limitations of current single antigen-targeted immunotherapies and to identify immune responses required for the achievement and, more importantly, maintenance of remission in childhood B-ALL. My results uncovered the ability of target-directed therapy to elicit epitope spreading, enabling the generation of a secondary immune response against additional non-targeted leukemia-associated antigens that contributes to sustaining durable remission. Importantly, these results also suggest that such diversification of protective immune response is limited in an immunological setting where immune tolerance towards leukemia-associated antigens is established early in the course of leukemia progression. Furthermore, I have shown the ability of TLR agonist-mediated immune modulation to target leukemia cells in bone marrow, and induce durable immune control of primary B-ALL cells. Finally, I have demonstrated that NKT cells as a population is capable of influencing disease progression in the Eμ-ret mouse by playing a role in immunoediting. Overall, these findings support that the generation of immune response with a broad specificity for range of leukemia-associated antigens contributes to the maintenance of remission. Furthermore, my results suggest that overcoming immune tolerance established against leukemia-associated antigens may be critical for maximizing the therapeutic benefits of immunotherapies for childhood B-ALL. Collectively, the therapeutic impact of innate immune modulation presented here in the context of B-ALL may contribute to the eradication of MRD, and thus reduce the risk of relaspse in MRD-positive patients.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat

Conservation of architectural heritage: Innovative approaches to enhance thermal comfort and promote sustainable usage in historic buildings

Heritage architecture, which considers the local climate, building materials, and construction methods, can contribute to the energy efficiency and sustainability of buildings. Retrofitting strategies can be applied to existing buildings to improve their energy performance while maintaining or enhancing their thermal comfort. This study involved an analysis of the indoor environment status at the Yonsei University Stimson Hall (completed in 1920), a building on the former Yonhee College (now Yonsei University). The analysis included temperature and humidity measurements over a one-year period in four rooms with different usage schedules and occupant types. It was found that the number of occupants and the usage schedule influenced the temperature distribution in the rooms. In addition, the effects of the retrofitting strategies on the building energy consumption were investigated. It was verified that the improvement in windows and the application of roof-type photovoltaic systems resulted in annual energy savings of up to 90.46% compared with reference buildings. In conclusion, the findings demonstrate the influence of variables such as usage schedule, occupant type, and season on the indoor climate, as well as the potential benefits and drawbacks of retrofitting strategies on energy consumption and thermal comfort

Memristor Neural Network Training with Clock Synchronous Neuromorphic System

Memristor devices are considered to have the potential to implement unsupervised learning, especially spike timing-dependent plasticity (STDP), in the field of neuromorphic hardware research. In this study, a neuromorphic hardware system for multilayer unsupervised learning was designed, and unsupervised learning was performed with a memristor neural network. We showed that the nonlinear characteristic memristor neural network can be trained by unsupervised learning only with the correlation between inputs and outputs. Moreover, a method to train nonlinear memristor devices in a supervised manner, named guide training, was devised. Memristor devices have a nonlinear characteristic, which makes implementing machine learning algorithms, such as backpropagation, difficult. The guide-training algorithm devised in this paper updates the synaptic weights by only using the correlations between inputs and outputs, and therefore, neither complex mathematical formulas nor computations are required during the training. Thus, it is considered appropriate to train a nonlinear memristor neural network. All training and inference simulations were performed using the designed neuromorphic hardware system. With the system and memristor neural network, the image classification was successfully done using both the Hebbian unsupervised training and guide supervised training methods

Prediction of the Seizure Suppression Effect by Electrical Stimulation via a Computational Modeling Approach

In this paper, we identified factors that can affect seizure suppression via electrical stimulation by an integrative study based on experimental and computational approach. Preferentially, we analyzed the characteristics of seizure-like events (SLEs) using our previous in vitro experimental data. The results were analyzed in two groups classified according to the size of the effective region, in which the SLE was able to be completely suppressed by local stimulation. However, no significant differences were found between these two groups in terms of signal features or propagation characteristics (i.e., propagation delays, frequency spectrum, and phase synchrony). Thus, we further investigated important factors using a computational model that was capable of evaluating specific influences on effective region size. In the proposed model, signal transmission between neurons was based on two different mechanisms: synaptic transmission and the electrical field effect. We were able to induce SLEs having similar characteristics with differentially weighted adjustments for the two transmission methods in various noise environments. Although the SLEs had similar characteristics, their suppression effects differed. First of all, the suppression effect occurred only locally where directly received the stimulation effect in the high noise environment, but it occurred in the entire network in the low noise environment. Interestingly, in the same noise environment, the suppression effect was different depending on SLE propagation mechanism; only a local suppression effect was observed when the influence of the electrical field transmission was very weak, whereas a global effect was observed with a stronger electrical field effect. These results indicate that neuronal activities synchronized by a strong electrical field effect respond more sensitively to partial changes in the entire network. In addition, the proposed model was able to predict that stimulation of a seizure focus region is more effective for suppression. In conclusion, we confirmed the possibility of a computational model as a simulation tool to analyze the efficacy of deep brain stimulation (DBS) and investigated the key factors that determine the size of an effective region in seizure suppression via electrical stimulation