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Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating the brain
Get PDFIn this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes
Cysteine-rich 61 inhibition attenuates hepatic insulin resistance and improves lipid metabolism in high-fat diet fed mice and HepG2 cells
Get PDFMetabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with insulin resistance development. Hepatic lipid accumulation and inflammation are considered the main drivers of hepatic insulin resistance in MASLD. Cysteine-rich 61 (Cyr61 also called CCN1), a novel secretory matricellular protein, is implicated in liver inflammation, and its role in MASLD is not clearly understood. Therefore, we investigated the role of Cyr61 in hepatic insulin resistance and lipid metabolism as major factors in MASLD pathogenesis. In high-fat diet (HFD)-fed C57BL/6J mice, Cyr61 was downregulated or upregulated via viral transduction. Measurements of glucose homeostasis, histological assessment of liver tissues, and gene expression and signaling pathways of lipogenesis, fatty acid oxidation, and inflammation were performed using liver samples from these mice. Cyr61 levels in HepG2 cells were reduced using RNAi-mediated gene knockdown. Inflammation and insulin resistance were evaluated using real-time polymerase chain reaction and western blotting. HFD/AAV-shCyr61 mice exhibited enhanced glucose tolerance via the protein kinase B pathway, reduced hepatic inflammation, decreased lipogenesis, and increased fatty acid oxidation. Notably, HFD/AAV-shCyr61 mice showed elevated protein expression of sirtuin 6 and phosphorylated-AMP-activated protein kinase. In vitro experiments demonstrated that inhibition of Cyr61 downregulated pro-inflammatory cytokines such as interleukin-1 beta, IL-6, and tumor necrosis factor-alpha via the nuclear factor kappa B/c-Jun N-terminal kinase pathway, and alleviated insulin resistance. Cyr61 affected hepatic inflammation, lipid metabolism, and insulin resistance. Inhibition of Cyr61 reduced inflammation, recovered insulin resistance, and altered lipid metabolism in vivo and in vitro. Therefore, Cyr61 is a potential therapeutic target in MASLD
Association between residing in municipalities facing population decline and satisfaction with neighboring healthcare infrastructure in older aged adults
Get PDFBackground: Many municipalities in rural areas of Korea are facing population decline due to the aging population phenomenon. This study examined the relationship between residing in municipalities facing population decline and satisfaction with nearby healthcare infrastructure in older aged adults. Methods: The 2021 Korea Community Health Survey (KCHS) data were used. Municipalities were classified as those not facing population decline, those at risk, and those facing population decline based on the Population Decline Index. The association between residing in municipalities facing population decline and satisfaction with nearby healthcare infrastructure was examined cross-sectionally using a multi-level logistic regression analysis. Satisfaction with available public transportation was concomitantly examined as it is related to accessing healthcare services. Results: Of the 58,568 individuals aged 65 years or above analyzed, 27,471 (46.9%) adults were residing in municipalities without population decline, 4,640 (7.9%) adults in municipalities at risk of population decline, and 26,457 (45.2%) in municipalities with population decline. Individuals living in municipalities with population decline were more likely to be dissatisfied with nearby healthcare infrastructure (OR 1.76, 95% CI 1.41–2.20). Similar tendencies were found for public transportation infrastructure (OR 1.67, 95% CI 1.38–2.03). Conclusions: Individuals residing in municipalities with declining populations are more likely to report dissatisfaction with nearby healthcare infrastructure and public transportation. These findings emphasize the importance of providing adequate medical infrastructure to reduce potential health-related disparities
Transcriptomic profiling of intermediate cell carcinoma of the liver
Get PDFBackground: Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet. Methods: RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma. Results: Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number–dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade. Conclusions: Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA
A Comparison of Tracheal Intubation Using Direct Laryngoscope and Video Laryngoscope in the Sellick and Trendelenburg Position with That Using Direct Laryngoscope in the Supine Sniffing Position: A Randomized Controlled Trial
Get PDFBackground: Tracheal intubation in the Sellick and Trendelenburg position (ST position) can prevent pulmonary aspiration but increase the difficulty of tracheal intubation. We compared tracheal intubation using video and direct laryngoscopy in the ST position with direct laryngoscopy in the supine sniffing position to evaluate the overall intubation performance. Methods: One hundred and twenty patients were randomly assigned to three groups: direct laryngoscope in the supine sniffing position (control), direct laryngoscope in the ST position (ST direct), and video laryngoscope in the ST position (ST video). The primary outcome was the intubation time; secondary outcomes included the first attempt success rate of tracheal intubation, intubation difficulty scale score, operator’s subjective assessment of intubation difficulty, and modified Cormack–Lehane grades. Results: The median intubation times were greater in the ST direct (36.0 s) and video (34.5 s) than the control (28.0 s) groups. The first attempt success rate decreased in the ST direct (77.5%) but not the video (95.0%) group compared with the control group (100%). Conclusions: The challenges of tracheal intubation in the ST position, aimed at reducing the risk of pulmonary aspiration, can be mitigated by using a video laryngoscope, despite slightly longer intubation times
Screening for RV Dysfunction Using Smartphone ECG Analysis App: Validation Study with Acute Pulmonary Embolism Patients
Get PDFBackground: Acute pulmonary embolism (PE) is a critical condition where the timely and accurate assessment of right ventricular (RV) dysfunction is important for patient management. Given the limited availability of echocardiography in emergency departments (EDs), an artificial intelligence (AI) application that can identify RV dysfunction from electrocardiograms (ECGs) could improve the treatment of acute PE. Methods: This retrospective study analyzed adult acute PE patients in an ED from January 2021 to December 2023. We evaluated a smartphone application which analyzes printed ECGs to generate digital biomarkers for various conditions, including RV dysfunction (QCG-RVDys). The biomarker’s performance was compared with that of cardiologists and emergency physicians. Results: Among 116 included patients, 35 (30.2%) were diagnosed with RV dysfunction. The QCG-RVDys score demonstrated significant effectiveness in identifying RV dysfunction, with a receiver operating characteristic–area under the curve (AUC) of 0.895 (95% CI, 0.829–0.960), surpassing traditional biomarkers such as Troponin I (AUC: 0.692, 95% CI: 0.536–0.847) and ProBNP (AUC: 0.655, 95% CI: 0.532–0.778). Binarized based on the Youden Index, QCG-RVDys achieved an AUC of 0.845 (95% CI: 0.778–0.911), with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.2% (95% CI: 82.4–100%), 77.8% (95% CI: 69.1–86.4%), 63.3% (95% CI: 54.4–73.9%), and 95.5% (95% CI: 90.8–100%), respectively, significantly outperforming all the expert clinicians, with their AUCs ranging from 0.628 to 0.683. Conclusions: The application demonstrates promise in rapidly assessing RV dysfunction in acute PE patients. Its high NPV could streamline patient management, potentially reducing the reliance on echocardiography in emergency settings
A comparative study of shade-matching performance using intraoral scanner, spectrophotometer, and visual assessment
Get PDFThis study aimed to explore the clinical applicability of the shade-matching function in intraoral scanners. This study measured the tooth colors of maxillary anterior dentitions of 83 adults using visual matching, a spectrophotometer, and a scanner according to two color systems: VITA Classical (VC) and VITA 3D-Master (V3D). Agreement between each method was assessed by weighted Cohen’s kappa coefficient (KW, α = 0.05). For V3D, the overall agreement between the scanner and spectrophotometer (KW = 0.498) was higher than that between the scanner and visual matching (KW = 0.473). Similarly, the agreement between the scanner and spectrophotometer (KW = 0.283) was higher than that between a scanner and visual matching (KW = 0.140) for VC. Regarding tooth position, the highest agreement between the scanner and spectrophotometer was observed on the right central incisor (KW = 0.542) for V3D. Tooth color measurement with a scanner was comparable to that with a spectrophotometer, especially on the central incisors when using the VITA 3D-Master system. A scanner could serve as an alternative to a spectrophotometer for shade selection. However, color matching should still be visually verified
Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia
No full textNanoparticles have been used in neurological research in recent years because of their blood–brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aβ) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aβ accumulation significantly increased in the 0.1 μg/μl MNPs@SiO2(RITC)-treated BV2 cells compared to the untreated control and 0.01 μg/μl MNPs@SiO2(RITC)-treated BV2 cells. Moreover, the MNPs@SiO2(RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO2(RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO2(RITC)-treated BV2 cells. Aβ accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO2(RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aβ accumulation
Assessing the potential of ChatGPT for psychodynamic formulations in psychiatry: An exploratory study
No full textAlthough there were several attempts to apply ChatGPT (Generative Pre-Trained Transformer) to medicine, little is known about therapeutic applications in psychiatry. In this exploratory study, we aimed to evaluate the characteristics and appropriateness of the psychodynamic formulations created by ChatGPT. Along with a case selected from the psychoanalytic literature, input prompts were designed to include different levels of background knowledge. These included naïve prompts, keywords created by ChatGPT, keywords created by psychiatrists, and psychodynamic concepts from the literature. The psychodynamic formulations generated from the different prompts were evaluated by five psychiatrists from different institutions. We next conducted further tests in which instructions on the use of different psychodynamic models were added to the input prompts. The models used were ego psychology, self-psychology, and object relations. The results from naïve prompts and psychodynamic concepts were rated as appropriate by most raters. The psychodynamic concept prompt output was rated the highest. Interrater agreement was statistically significant. The results from the tests using instructions in different psychoanalytic theories were also rated as appropriate by most raters. They included key elements of the psychodynamic formulation and suggested interpretations similar to the literature. These findings suggest potential of ChatGPT for use in psychiatry