Aims: Antisaccadic eye movements, requiring inhibition of a saccade toward a briefly appearing peripheral target, are known to be impaired in schizophrenia. Previous neuroimaging studies have ...indicated that patients with schizophrenia show diminished activations in the frontal cortex and basal ganglia. These studies used target fixation as a baseline condition. However, if the levels of brain activities at baseline are not compatible between patients and healthy subjects, between‐group comparison on antisaccade‐related activations is consequently invalidated. One possibility is that patients with schizophrenia may present with greater activation during fixation than healthy subjects. In order to examine this possibility, here we investigated brain activities associated with antisaccade in the two groups without using target fixation at baseline.
Methods: Functional brain images were acquired during prosaccades and antisaccades in 18 healthy subjects and 18 schizophrenia patients using a box‐car functional magnetic resonance imaging design. Eye movements were measured during scanning.
Results: In the patient group, the elevated activities in the dorsolateral prefrontal cortex (DLPFC) and thalamus, normally seen in antisaccade tasks relative to saccade tasks, were no longer observed. Moreover, in normal subjects, activities in the DLPFC and thalamus were greater during the antisaccade task than during the saccade task. In patients, no such difference was observed between the two tasks, suggesting that these brain regions are likely to be highly activated even by a simple task such as fixation. In particular, the DLPFC and thalamus in patients were not activated at a level commensurate with the difficulty of the tasks presented.
Conclusions: From these results, it is suggested that schizophrenia entails dysfunctions in the fronto‐striato‐thalamo‐cortical network associated with motor function control.
Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue.
A ...total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data.
The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001).
In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.
For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. ...However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results.
A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence.
Logistic multivariate analysis showed platelet count (≤12 × 104/μL) (odds ratio OR 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/μL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001).
The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.
Background/aim
Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in ...recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy.
Methods
From 2000 to 2022, 528 patients with Child–Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated.
Results
Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each
P
< 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each
P
< 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each
P
< 0.05).
Conclusion
HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.
To elucidate whether there is a common or a different neural substrate deficit between schizophrenia and epileptic psychosis, we have investigated brain activation patterns during various eye ...movement tasks using functional magnetic resonance imaging (fMRI). Compared with normal controls, low capacity or inefficiency in frontal function during visually guided saccade task and striate–thalamic hypo-function during anti-saccade task was found both in schizophrenia and epileptic psychosis. Therefore, these findings may not be attributable to disease but to a psychotic state. On the other hand, right hemisphere hypo-function during a smooth pursuit eye movement (SPEM) task with attention-enhanced procedure was found only in schizophrenia and may be a specific finding in schizophrenia.
Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous ...interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism.
Ischemic preconditioning (IPC) is the most powerful endogenous cardioprotective form of cellular adaptation. However, the inhibitory or augmenting mechanism underlying cardioprotection via IPC ...remains largely unknown. Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible potent negative feedback regulator of the signal transducer and activator of transcription-3 (STAT3) signaling pathway. Here, we aimed to determine whether cardiac SOCS3 deficiency and IPC would synergistically reduce infarct size after myocardial ischemia reperfusion injury. We evaluated STAT3 activation and SOCS3 induction after ischemic conditioning (IC) using western blot analysis and real-time PCR, and found that myocardial IC alone transiently activated myocardial STAT3 and correspondingly induced SOCS3 expression in wild-type mice. Compared with wild-type mice, cardiac-specific SOCS3 knockout (SOCS3-CKO) mice showed significantly greater and more sustained IC-induced STAT3 activation. Following ischemia reperfusion, IPC substantially reduced myocardial infarct size and significantly enhanced STAT3 phosphorylation in SOCS3-CKO mice compared to in wild-type mice. Real-time PCR array analysis revealed that SOCS3-CKO mice after IC exhibited significantly increased expressions of several anti-apoptotic genes and SAFE pathway-related genes. Moreover, real-time PCR analysis revealed that myocardial IC alone rapidly induced expression of the STAT3-activating cytokine erythropoietin in the kidney at 1 h post-IC. We also found that the circulating erythropoietin level was promptly increased at 1 h after myocardial IC. Myocardial SOCS3 deficiency and IPC exert synergistic effects in the prevention of myocardial injury after ischemia reperfusion. Our present results suggest that myocardial SOCS3 is a potent inhibitor of IPC-induced cardioprotection, and that myocardial SOCS3 inhibition augment IPC-mediated cardioprotection during ischemia reperfusion injury.
Abstract
Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ...ventricle predominantly expresses alternative complement pathway-related genes, including
Cfd
and
C3aR1
. Complement 3 (
C3
)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd).
Cfd
-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.
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