Investigating the integrate and fire model as the limit of a random discharge model: a stochastic analysis perspective

In the mean field integrate-and-fire model, the dynamics of a typical neuron within a large network is modeled as a diffusion-jump stochastic process whose jump takes place once the voltage reaches a threshold. In this work, the main goal is to establish the convergence relationship between the regularized process and the original one where in the regularized process, the jump mechanism is replaced by a Poisson dynamic, and jump intensity within the classically forbidden domain goes to infinity as the regularization parameter vanishes. On the macroscopic level, the Fokker-Planck equation for the process with random discharges (i.e. Poisson jumps) are defined on the whole space, while the equation for the limit process is on the half space. However, with the iteration scheme, the difficulty due to the domain differences has been greatly mitigated and the convergence for the stochastic process and the firing rates can be established. Moreover, we find a polynomial-order convergence for the distribution by a re-normalization argument in probability theory. Finally, by numerical experiments, we quantitatively explore the rate and the asymptotic behavior of the convergence for both linear and nonlinear models

Bibliometric and visual analysis of intraoperative hypotension from 2004 to 2022

BackgroundIntraoperative hypotension (IOH) is a common complication occurring in surgical practice. This study aims to comprehensively review the collaboration and impact of countries, institutions, authors, journals, keywords, and critical papers on intraoperative hypotension from the perspective of bibliometric, and to evaluate the evolution of knowledge structure clustering and identify research hotspots and emerging topics.MethodsArticles and reviews related to IOH published from 2004 to 2022 were retrieved from the Web of Science Core Collection. Bibliometric analyses and visualization were conducted on Excel, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 1,784 articles and reviews were included from 2004 to 2022. The number of articles on IOH gradually increased in the past few years, and peaked in 2021. These publications were chiefly from 1,938 institutions in 40 countries, led by America and China in publications. Sessler Daniel I published the most papers and enjoyed the highest number of citations. Analysis of the journals with the most outputs showed that most journals concentrated on perioperative medicine and clinical anesthesiology. Delirium, acute kidney injury and vasoconstrictor agents are the current and developing research hotspots. The keywords “Acute kidney injury”, “postoperative complication”, “machine learning”, “risk factors” and “hemodynamic instability” may also become new trends and focuses of the near future research.ConclusionThis study uses bibliometrics and visualization methods to comprehensively review the research on intraoperative hypotension, which is helpful for scholars to better understand the dynamic evolution of IOH and provide directions for future research

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a tissue biomarker for detection of early Hepatocellular carcinoma in patients with cirrhosis

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors occurring mainly in patients with chronic liver disease. Detection of early HCC is critically important for treatment of these patients. Methods We employed a proteomic profiling approach to identify potential biomarker for early HCC detection. Based on Barcelona Clinic Liver Cancer (BCLC) staging classification, 15 early HCC and 25 late HCC tissue samples from post-operative HCC patients and their clinicopathological data were used for the discovery of biomarkers specific for the detection of early HCC. Differential proteins among cirrhotic, early, and late tissue samples were separated by two-dimensional gel electrophoresis (2-DE) and subsequently identified by mass spectrometry (MS). Receiver operating characteristic (ROC) curves analysis were performed to find potential biomarkers associated with early HCC. Diagnosis performance of the biomarker was obtained from diagnosis test. Results Protein spot SSP2215 was found to be significantly overexpressed in HCC, particularly in early HCC, and identified as heterogeneous nuclear ribonucleoprotein K (hnRNP K) by tandem mass spectrometry (MALDI TOF/TOF). The overexpression in HCC was subsequently validated by western blot and immunohistochemistry. ROC curve analysis showed that hnRNP K intensity could detect early HCC at 66.67 % sensitivity and 84 % specificity, which was superior to serum α-fetoprotein (AFP) in detection of early HCC. Furthermore, the diagnosis test demonstrated, when combined with hnRNP K and serum AFP as biomarker panel to detect early HCC at different cut-off value, the sensitivity and specificity could be enhanced to 93.33 % and 96 %, respectively. Conclusions hnRNP K is a potential tissue biomarker, either alone or in combination with serum AFP, for detection of early HCC. High expression of hnRNP K could be helpful to discriminate early HCC from a nonmalignant nodule, especially for patients with liver cirrhosis.</p

Aire-Overexpressing Dendritic Cells Induce Peripheral CD4+ T Cell Tolerance

Autoimmune regulator (Aire) can promote the ectopic expression of peripheral tissue-restricted antigens (TRAs) in thymic medullary epithelial cells (mTECs), which leads to the deletion of autoreactive T cells and consequently prevents autoimmune diseases. However, the functions of Aire in the periphery, such as in dendritic cells (DCs), remain unclear. This study’s aim was to investigate the effect of Aire-overexpressing DCs (Aire cells) on the functions of CD4+ T cells and the treatment of type 1 diabetes (T1D). We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4+ T cells in STZ-T1D mouse-derived splenocytes. Furthermore, following insulin stimulation, Aire cells decreased the number of CD4+ IFN-γ+ T cells in both STZ-T1D and WT mouse-derived splenocytes and reduced the expression levels of TCR signaling molecules (Ca2+ and p-ERK) in CD4+ T cells. We observed that Aire cells-induced CD4+ T cells could delay the development of T1D. In summary, Aire-expressing DCs inhibited TCR signaling pathways and decreased the quantity of CD4+IFN-γ+ autoreactive T cells. These data suggest a mechanism for Aire in the maintenance of peripheral immune tolerance and provide a potential method to control autoimmunity by targeting Aire