Exploring aryl hydrocarbon receptor expression and distribution in the tumor microenvironment, with a focus on immune cells, in various solid cancer types

IntroductionAryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers.MethodsHere, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression.ResultsOur findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC).DiscussionThese findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies

Biomaterials to Prevent Post-Operative Adhesion

Surgery is performed to treat various diseases. During the process, the surgical site is healed through self-healing after surgery. Post-operative or tissue adhesion caused by unnecessary contact with the surgical site occurs during the normal healing process. In addition, it has been frequently found in patients who have undergone surgery, and severe adhesion can cause chronic pain and various complications. Therefore, anti-adhesion barriers have been developed using multiple biomaterials to prevent post-operative adhesion. Typically, anti-adhesion barriers are manufactured and sold in numerous forms, such as gels, solutions, and films, but there are no products that can completely prevent post-operative adhesion. These products are generally applied over the surgical site to physically block adhesion to other sites (organs). Many studies have recently been conducted to increase the anti-adhesion effects through various strategies. This article reviews recent research trends in anti-adhesion barriers

Development of a Lidocaine-Loaded Alginate/CMC/PEO Electrospun Nanofiber Film and Application as an Anti-Adhesion Barrier

Surgery, particularly open surgery, is known to cause tissue/organ adhesion during healing. These adhesions occur through contact between the surgical treatment site and other organ, bone, or abdominal sites. Fibrous bands can form in unnecessary contact areas and cause various complications. Consequently, film- and gel-type anti-adhesion agents have been developed. The development of sustained drug delivery systems is very important for disease treatment and prevention. In this study, the drug release behavior was controlled by crosslinking lidocaine-loaded alginate/carboxymethyl cellulose (CMC)/polyethylene oxide (PEO) nanofiber films prepared by electrospinning. Lidocaine is mainly used as an anesthetic and is known to have anti-adhesion effects. Our results show that drug release is regulated by the crosslinking degree of the lidocaine-loaded alginate/CMC/PEO film. The drug release behavior was confirmed by HPLC, and, as a result, an excellent anti-adhesion barrier was developed that can be applied to treat patients in the medical field

Planar coil-based contact-mode magnetic stimulation: synaptic responses in hippocampal slices and thermal considerations

Abstract Implantable magnetic stimulation is an emerging type of neuromodulation using coils that are small enough to be implanted in the brain. A major advantage of this method is that stimulation performance could be sustained even though the coil is encapsulated by gliosis due to foreign body reactions. Magnetic fields can induce indirect electric fields and currents in neurons. Compared to transcranial magnetic stimulation, the coil size used in implantable magnetic stimulation can be greatly reduced. However, the size reduction is accompanied by an increase in coil resistance. Hence, the coil could potentially damage neurons from the excess heat generated. Therefore, it is necessary to study the stimulation performance and possible thermal damage by implantable magnetic stimulation. Here, we devised contact-mode magnetic stimulation (CMS), wherein magnetic stimulation was applied to hippocampal slices through a customized planar-type coil underneath the slice in the contact mode. With acute hippocampal slices, we investigated the synaptic responses to examine the field excitatory postsynaptic responses of CMS and the temperature rise during CMS. A long-lasting synaptic depression was exhibited in the CA1 stratum radiatum after CMS, while the temperature remained in a safe range so as not to seriously affect the neural responses

Introduction of Infection Prevention Tracheal Intubation Protocol during the COVID-19 Pandemic Is Not Associated with First-Pass Success Rates of Endotracheal Intubation in the Emergency Department: A Before-and-After Comparative Study

Aerosols and droplets have put healthcare workers performing airway management at high risk of contracting coronavirus disease 2019 (COVID-19). Experts have developed endotracheal intubation (ETI) guidelines and protocols to protect intubators from infection. We aimed to determine whether changes in the emergency department (ED) intubation protocol to prevent COVID-19 infection were associated with first-pass success (FPS) rates in ETI. We used data from the airway management registries in two academic EDs. The study was divided into pre-pandemic (January 2018 to January 2020) and pandemic (February 2020 to February 2022) periods. We selected 2476 intubation cases, including 1151 and 1325 cases recorded before and during the pandemic, respectively. During the pandemic, the FPS rate was 92.2%, which did not change significantly, and major complications increased slightly but not significantly compared with the pre-pandemic period. The OR for the FPS of applying infection prevention intubation protocols was 0.72 (p = 0.069) in a subgroup analysis, junior emergency physicians (PGY1 residents) had an FPS of less than 80% regardless of pandemic protocol implementation. The FPS rate of senior emergency physicians in physiologically difficult airways decreased significantly during the pandemic (98.0% to 88.5%). In conclusion, the FPS rate and complications for adult ETI performed by emergency physicians using COVID-19 infection prevention intubation protocols were similar to pre-pandemic conditions

Association between Glasgow Coma Scale in Early Carbon Monoxide Poisoning and Development of Delayed Neurological Sequelae: A Meta-Analysis

A significant number of people experience delayed neurologic sequelae after acute carbon monoxide (CO) poisoning. The Glasgow Coma Scale (GCS) can be used to predict delayed neurologic sequelae occurrence efficiently and without any restrictions. Here, we investigated the association between a low GCS score observed in cases of early CO poisoning and delayed neurologic sequelae development through a meta-analysis. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for studies on GCS as a predictor of delayed neurologic sequelae occurrence in patients with CO poisoning in June 2021. Two reviewers independently extracted study characteristics and pooled data. We also conducted subgroup analyses for the cutoff point for GCS. To assess the risk of bias of each included study, we used the quality in prognosis studies tool. We included 2328 patients from 10 studies. With regard to patients with acute CO poisoning, in the overall pooled odds ratio (OR) of delayed neurologic sequelae development, those with a low GCS score showed a significantly higher value and moderate heterogeneity (OR 2.98, 95% confidence interval (CI) 2.10–4.23, I2 = 33%). Additionally, in subgroup analyses according to the cutoff point of GCS, the development of delayed neurologic sequelae was still significantly higher in the GCS < 9 group (OR 2.80, 95% CI 1.91–4.12, I2 = 34%) than in the GCS < 10 or GCS < 11 groups (OR 4.24, 95% CI 1.55–11.56, I2 = 48%). An initial low GCS score in patients with early CO poisoning was associated with the occurrence of delayed neurologic sequelae. Additionally, GCS was quickly, easily, and accurately assessed. It is therefore possible to predict delayed neurologic sequelae and establish an active treatment strategy, such as hyperbaric oxygen therapy, to minimize neurological sequelae using GCS

The Prognostic Value of Optic Nerve Sheath Diameter/Eyeball Transverse Diameter Ratio in the Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients

Background and objectives: The optic nerve sheath diameter (ONSD) is indicative of elevated intracranial pressure. However, the usefulness of the ONSD for predicting neurologic outcomes in cardiac arrest survivals has been debatable. Reportedly, the ONSD/eyeball transverse diameter (ETD) ratio is a more reliable marker for identifying intracranial pressure than sole use of ONSD. Materials and Methods: This retrospective study aimed to investigate the prognostic value of the ONSD/ETD ratio in out-of-hospital cardiac arrest (OHCA) patients. We studied the brain computed tomography scans of adult OHCA patients with return of spontaneous circulation, who visited a single hospital connected with a Korean university between January 2015 and September 2020. We collected baseline characteristics and patient information from electronic medical records and ONSD and ETD were measured by two physicians with a pre-defined protocol. According to their neurologic outcome upon hospital discharge, patients were divided into good neurologic outcome (GNO; cerebral performance category [CPC] 1–2) and poor neurologic outcome (PNO; CPC 3–5) groups. We evaluated the ONSD/ETD ratio between the GNO and PNO groups to establish its prognostic value for neurologic outcomes. Results: Of the 100 included patients, 28 had GNO. Both the ONSD and ETD were not significantly different between the two groups (ONSD, 5.48 mm vs. 5.66 mm, p = 0.054; ETD, 22.98 mm vs. 22.61 mm, p = 0.204). However, the ONSD/ETD ratio was significantly higher in the PNO group in the univariate analysis (0.239 vs. 0.255, p = 0.014). The area under the receiver operating characteristic curve of ONSD/ETD ratio for predicting PNO was 0.66 (95% confidence interval, 0.56–0.75; p = 0.006). There was no independent relationship between the ONSD/ETD ratio and PNO in multivariate analysis (aOR = 0.000; p = 0.173). Conclusions: The ONSD/ETD ratio was more reliable than sole use of ONSD and might be used to predict neurologic outcomes in OHCA survivors

Detection and Genotyping of Mycobacterium Species from Clinical Isolates and Specimens by Oligonucleotide Array

Identification of pathogenic Mycobacterium species is important for a successful diagnosis of mycobacteriosis. The purpose of this study was to develop an oligonucleotide array which could detect and differentiate mycobacteria to the species level by using the internal transcribed spacer (ITS) sequence. Using a genus-specific probe and 20 species-specific probes including two M. avium-intracellulare complex (MAC)-specific probes, we have developed an ITS-based oligonucleotide array for the rapid and reliable detection and discrimination of M. tuberculosis, MAC, M. fortuitum, M. chelonae, M. abscessus, M. kansasii, M. gordonae, M. scrofulaceum, M. szulgai, M. vaccae, M. xenopi, M. terrae, M. flavescens, M. smegmatis, M. malmoense, M. simiae, M. marinum, M. ulcerans, M. gastri, and M. leprae. All mycobacteria were hybridized with a genus-specific probe (PAN-03) for detection of the genus Mycobacterium. Mycobacterial species were expected to show a unique hybridization pattern with species-specific probes, except for M. marinum and M. ulcerans, which were not differentiated by ITS-based probe. Among the species-specific probes, two kinds of species-specific probes were designed for MAC in which there were many subspecies. The performance of the oligonucleotide array assay was demonstrated by using 46 reference strains, 149 clinical isolates, and 155 clinical specimens. The complete procedure (DNA extraction, PCR, DNA hybridization, and scanning) was carried out in 4.5 h. Our results indicated that the oligonucleotide array is useful for the identification and discrimination of mycobacteria from clinical isolates and specimens in an ordinary clinical laboratory

Remote Gaze Tracking System on a Large Display

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