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• We predict the neurological prognosis of cardiac arrest patients using brain CT biomarkers. • We extracted 1131 biomarkers from two volumes of interest on brain CT images. • Various combinations of feature selections and ML algorithms were investigated. • The gray level with the maximum histogram gradient provided a high classification performance. • Our predictor may promote routine CT imaging for decision support in acute care. We aimed to predict the neurological prognosis of cardiac arrest (CA) patients using quantitative imaging biomarkers extracted from brain computed tomography images. We retrospectively enrolled 86 CA patients (good prognosis, 32; poor prognosis, 54) who were treated at three hospitals between 2017 and 2019. We then extracted 1131 quantitative imaging biomarkers from whole-brain and local volumes of interest in the computed tomography images of the patients. The data were split into training and test sets containing 60 and 26 samples, respectively, and the training set was used to select representative quantitative imaging biomarkers for classification. In univariate analysis, the classification was evaluated using the p -value of the Brunner–Munzel test and area under the receiver operating characteristic curve (AUC) for the test set. In multivariate analysis, machine learning models reflecting nonlinear and complex relations were trained, and they were evaluated using the AUC on the test set. The best performance provided p = 0.009 (<0.01) and an AUC of 0.775 (95% confidence interval, 0.590–0.960) for the univariate analysis and an AUC of 0.813 (95% confidence interval, 0.640–0.985) for the multivariate analysis. Overall, the gray level with the maximum gradient in the histogram of the three-dimensionally low-pass-filtered image was an important feature for prediction across the analyses. Quantitative imaging biomarkers can be used in neurological prognosis prediction for CA patients. Relevant biomarkers may contribute to protocolized computed tomography image acquisition to ensure proper decision support in acute care. [ABSTRACT FROM AUTHOR]

Introduction: Patients with myotonic dystrophy type 1 have several cardiac abnormalities, especially myocardial conduction disorders. Few studies have investigated cerebral infarction. We investigated the frequency of both symptomatic and asymptomatic ischemic strokes in patients with myotonic dystrophy type 1.Methods: Patients who were diagnosed with myotonic dystrophy type 1 using genetic testing or clinical examinations at Asahikawa Medical Center were included. We retrospectively reviewed their medical history, neuroradiological imaging, electrocardiograms, and treatment. Their CHADS2 and CHA2DS2-VASc scores were calculated.Result: A total of 108 patients were diagnosed with myotonic dystrophy type 1. Magnetic resonance imaging was performed in 72 and 1 patient whose results were not available was excluded. Among these, 2 patients had atrial flutter and 3 had atrial fibrillation. Regarding the CHADS2 score, 11 patients scored more than 2. Regarding the CHA2DS2-VASc score, 22 patients scored more than 2. Ischemic strokes were found in 9 patients with 1 having an atrial flutter and 4 having atrial fibrillation. All patients with stroke had CHADS2 and CHA2DS2-VASc scores higher than 2. There were significant differences between the 2 groups in atrial fibrillation (P < .001), CHADS2 score (P < .001), and CHA2DS2-VASc score (P < .001).Conclusions: Ischemic stroke in patients with myotonic dystrophy type 1 is associated with atrial fibrillation. The CHADS2 score seems to be useful for the management of patients with myotonic dystrophy type 1. Repeated electrocardiograms are necessary for managing these patients. [ABSTRACT FROM AUTHOR]

Endoscopic remission is known to be defined as a Mayo endoscopic subscore (MES) of ≤1 in patients with ulcerative colitis (UC). However, some individuals experience relapse even after showing endoscopic remission under white-light imaging (WLI), and no tool exists that can detect these individuals. The aim of this study was to clarify the usefulness of texture and color enhancement imaging (TXI) in the assessment of inflammation in patients with UC. This was a prospective, single-arm, observational study conducted at a university hospital. From January 2021 to December 2021, 146 UC patients with endoscopic remission were enrolled. Images were evaluated by WLI, TXI, and pathologic evaluation, followed by prognostic studies. The primary endpoint of the study was the cumulative relapse of UC in each TXI score. The secondary endpoints were the association between TXI and pathologic scores, predictors of relapse, and interobserver agreement between the MES and TXI scores. Patients with TXI score 2 had significantly lower UC relapse-free rates than did those with TXI scores 0-1 (log-rank test, P <.01). When pathologic remission was defined as Matts grade ≤2, the rate of pathologic remission decreased significantly with higher TXI scores (P =.01). In multivariate analysis, TXI score 2 was the only risk factor for UC relapse (P <.01; hazard ratio, 4.16; 95% confidence interval, 1.72-10.04). Interobserver agreement on the TXI score was good (κ = 0.597-0.823). TXI can be used to identify populations with poor prognosis in MES 1, for whom treatment intensification has been controversial. [ABSTRACT FROM AUTHOR]

In the mouse intestinal epithelium, Lgr5+ stem cells are vulnerable to injury, owing to their predominantly cycling nature, and their progenies de-differentiate to replenish the stem cell pool. However, how human colonic stem cells behave in homeostasis and during regeneration remains unknown. Transcriptional heterogeneity among colonic epithelial cells was analyzed by means of single-cell RNA sequencing analysis of human and mouse colonic epithelial cells. To trace the fate of human colonic stem or differentiated cells, we generated LGR5-tdTomato, LGR5-iCasase9-tdTomato, LGR5-split-Cre, and KRT20-ERCreER knock-in human colon organoids via genome engineering. p27+ dormant cells were further visualized with the p27-mVenus reporter. To analyze the dynamics of human colonic stem cells in vivo, we orthotopically xenotransplanted fluorescence-labeled human colon organoids into immune-deficient mice. The cell cycle dynamics in xenograft cells were evaluated using 5-ethynyl-2′-deoxyuridine pulse-chase analysis. The clonogenic capacity of slow-cycling human stem cells or differentiated cells was analyzed in the context of homeostasis, LGR5 ablation, and 5-fluorouracil–induced mucosal injury. Single-cell RNA sequencing analysis illuminated the presence of nondividing LGR5+ stem cells in the human colon. Visualization and lineage tracing of slow-cycling LGR5+p27+ cells and orthotopic xenotransplantation validated their homeostatic lineage-forming capability in vivo, which was augmented by 5-FU–induced mucosal damage. Transforming growth factor–β signaling regulated the quiescent state of LGR5+ cells. Despite the plasticity of differentiated KRT20+ cells, they did not display clonal growth after 5-FU–induced injury, suggesting that occupation of the niche environment by LGR5+p27+ cells prevented neighboring differentiated cells from de-differentiating. Our results highlight the quiescent nature of human LGR5+ colonic stem cells and their contribution to post-injury regeneration. [Display omitted] Tissue engineering technology revealed that human colonic stem cells are slow-cycling and resistant to chemotherapy, which challenges the current understanding of mucosal regeneration based on mouse-centered research. [ABSTRACT FROM AUTHOR]

CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon. [Display omitted] • Indigo naturalis (IN) increases Helios+ Tregs in the colon • IN-induced Tregs are localized near the crypt top in the colon • AhR signaling in colonic epithelial cells is indispensable for Treg accumulation • IN treatment induces colonic Tregs and suppresses experimental colitis Yoshimatsu et al. show that aryl hydrocarbon receptor (AhR) signaling in ECs governs the induction and localization of indigo naturalis (IN)-induced Helios+ Tregs in the colon both in the murine model and in ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

Abstract: The changes of physiological conditions in obesity could make the treatment with CyA more complicated and heterogeneous; in particular, the elevation of serum lipids and fatty liver have great potential to affect the biodistribution and metabolism of CyA. The aim of the present study is to investigate the effect of obesity on the pharmacokinetics of CyA in high-fat-fed rats (HF rats). After intravenous and intraduodenal administration to HF rats, AUC0−∞ of CyA was significantly increased in comparison with that of controls (2.8- and 1.5-fold, respectively), and the distribution volume at steady state (Vdss) in HF rats was significantly decreased to 56%, possibly due to increased lipoprotein binding ratio of CyA. In contrast, t1/2 did not show notable changes, despite the decrease of Vdss in HF rats. The hepatic distribution of CyA in HF rats was significantly higher than that in controls. It was considered that, as a lipid complex, CyA uptake via the lipoprotein receptor into hepatocytes could increase in HF rats and counteract the decrease of Vdss, resulting in comparable t1/2. It was noted that the oral bioavailability of CyA was significantly decreased to 54% in HF rats, whereas the metabolism in intestinal and hepatic microsomes indicated no notable difference in the first-pass effect of CyA. These results suggested that when switching from a CyA injectable formulation to an oral one in obese patients, the attenuation of oral bioavailability should be taken into account in a dose adjustment, even though its mechanism has been unclear and warrants further investigation. [Copyright &y& Elsevier]

To date, only few reports are available regarding the long-term outcome of borderline personality disorder (BPD) in Japan. We conducted a retrospective follow-up study on the long-term outcome and predictive factors of BPD in Japan. Of 72 patients who received treatment at Fukuoka University Hospital between 1973 and 1989 and met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria fur BPD retrospectively, 19 patients (26.4%) were followed up. We evaluated global outcome at follow-up using the Global Assessment of Functioning Scale scored from a completed self-reported questionnaire. The mean Global Assessment of Functioning score was 60.7, which meant fair to good functioning. The suicide rate was 6.9% (5/72). Using a logistic regression model, over involvement in family relationships and the number of medical facilities where patient was previously treated predicted poor outcome. These results are similar to those reported in the United States and Canada, except for the result that Japanese patients with BPD are more likely to live with their original family at follow-up than American patients. [ABSTRACT FROM AUTHOR]

A 70-year-old man with multiple ischemic strokes was diagnosed with cardiac embolism and treated with dabigatran. Three months later, he suddenly developed vertigo and vomiting. Magnetic resonance imaging, showed recurrent lesions and blood tests revealed hypercoagulability, hypoproteinemia, and elevated cytokeratin 19 fragments that serve as a tumor marker of lung cancer. Chest computed tomography showed there were small nodules in bilateral lungs and swollen mediastinal lymph nodes. A conclusive diagnosis was impossible because the patient declined invasive procedures. We suspected primary lung cancer and diagnosed concomitant arterial thrombosis. We initially administered low-molecular-weight heparin, which we later changed to vitamin K antagonist. Although stroke did not recur thereafter, liver metastasis resulted in death 6 months later. The effectiveness of novel oral anticoagulants for preventing the Trousseau syndrome remains unclear. Further study is needed to prevent venous and arterial thromboses arising from the Trousseau syndrome. [Copyright &y& Elsevier]

A 67-year-old right-handed woman experienced a sudden anterograde and retrograde short-term memory deficit that recovered on the next day. Magnetic resonance imaging (MRI) showed a spotty high-intensity lesion in the left putamen in the diffusion-weighted and fluid-attenuated inversion recovery images. Transient global amnesia due to lacunar infarction of the left putamen was diagnosed. Transient global amnesia is characterized by a sudden onset of anterograde amnesia that disappears within 24 hours. The cause of transient global amnesia is still uncertain. Some studies with MRI showed small lesions in the hippocampus at 24-74 hours after the episode. These lesions disappear within several weeks. However, our case of transient global amnesia showed a small lesion in the left putamen, not the hippocampus. Some studies with functional MRI reported that the stratum plays an important role in short-term memory and cognitive function. This case showed only a left putamen lesion, which indicates that a putamen lesion can cause transient global amnesia. [ABSTRACT FROM AUTHOR]

Abstract: A major clinical problem encountered with the use of non-steroidal anti-inflammatory drugs (NSAIDs) is gastrointestinal complications. We have previously suggested that both decreases in prostaglandin E2 (PGE2) levels and mucosal apoptosis are involved in the development of NSAID-produced gastric lesions and that this apoptosis is mediated by an increase in the intracellular Ca2+ concentration and the resulting endoplasmic reticulum (ER) stress response and mitochondrial dysfunction. Celecoxib and rebamipide are being used clinically as a safer NSAID and an anti-ulcer drug, respectively. In this study, we have examined the effect of rebamipide on celecoxib-induced production of gastric lesions. In mice pre-administered with a low dose of indomethacin, orally administered rebamipide suppressed celecoxib-induced mucosal apoptosis and lesion production but did not decrease in PGE2 levels in the stomach. Rebamipide also suppressed celecoxib-induced increases in intracellular Ca2+ concentration, the ER stress response, mitochondrial dysfunction and apoptosis in vitro. We also found that rebamipide suppresses the increases in intracellular Ca2+ concentration induced by an activator of voltage-dependent L-type Ca2+ channels and that another blocker of this channel suppresses celecoxib-induced increases in intracellular Ca2+ concentration. These results suggest that celecoxib activates voltage-dependent L-type Ca2+ channels and that rebamipide blocks this activation, resulting in suppression of celecoxib-induced apoptosis. We believe that this novel activity of rebamipide may play an important role in the protection of gastric mucosa against the formation of celecoxib-induced lesions. [Copyright &y& Elsevier]