Few population-based surveys of childhood arterial ischemic stroke (AIS) have been conducted in Asian countries. The aim of this study was to investigate the clinical features, time to diagnosis, and ...prognosis of childhood AIS in a population-based cohort in Japan.
Children aged 29 days-15 years 11 months old, residing in the Aichi Prefecture of Japan with radiologically confirmed AIS during 2010-2014, were identified retrospectively through questionnaires. We analyzed 40 children (23 boys, 17 girls; median age, 7 years 3 months), and collected time interval information of 26 patients. The time from clinical onset to first physician assessment and the time to AIS diagnosis were calculated.
The most common presentation was paralysis or paresis in 27 patients (71%). No underlying disorders or possible trigger factors were identified in 14 patients (35%). The median time from symptom onset to first physician assessment was 2.9 h. The median time from symptom onset to the confirmed AIS diagnosis was 27.0 h. The diagnosis of AIS was made in the first 6 h after onset of symptoms in 27% of patients for whom the time was available. Radiological diagnosis took longer than 24 h in 54% of these patients.
Long in-hospital delays exist in the diagnosis of AIS in children, likely due to lack of awareness of stroke by doctors. Further efforts to increase public and physician awareness of childhood stroke are needed to ensure early diagnosis and treatment.
Background & Aims Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) ...infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes associated with favorable response. Methods We analyzed 52 liver and 114 blood samples obtained from patients with HCV genotype 1b. We used reverse transcription-real time polymerase chain reaction to analyze expression levels of IL28 and several interferon stimulated genes (ISGs), including MxA , double stranded RNA dependent protein kinase ( PKR ), 2′–5′ oligo-nucleotide synthetase ( OAS1 ), ISG15 , and SOCS1. Results Interestingly, expression of IL28 was significantly lower in patients with the response-favorable rs8099917 TT genotype compared to those with TG or GG genotypes ( p <0.005). In hepatic cells, expression of MxA , PKR , OAS1 , and ISG15 were also significantly lower in rs8099917 TT patients ( p <0.001, p = 0.005, p = 0.001, p <0.001, respectively), whereas in peripheral blood mononuclear cells ISG expression levels did not differ significantly. Among patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28 , MxA , PKR , OAS1 , and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA ( p = 0.001, 0.004, 0.014, 0.051, and 0.015, respectively). Conclusions Expression levels of ISGs are differentially regulated in the liver and peripheral blood. The mechanism underlying the expression levels of IL28 and ISGs and the correlation with the effect of the therapy should be further investigated.
To provide the necessary oxygen for plant growth, the effectiveness of different generating methods of microbubbles (MB), a gas-water circulation type or a pressurization type (pressurization ...treatment), was investigated by comparing the growth characteristics and morphological observation of Brassica campestris L. var. Komatsuna Matsum. The plant growth in the pressurization treatment were significantly less than those in the circulation treatment at 3 weeks after planting. In plants grown in the pressurization treatment, epidermal cell abrasion and plasmolysis, indicators of cell death, were observed in root tip cells at 3 weeks after planting. The growth inhibition of plant in the pressurization treatment is suggested to be related to the oxidization of Fe in the nutrient solution under super-saturated dissolved oxygen conditions, the generation of hydroxyl radicals from MB, the oxidization of the root tip cell membrane, and osmotic stress to the roots.
A recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated ...psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome.
A selective review of the literature including studies from our department was performed.
Longitudinal structural neuroimaging studies on schizophrenia revealed that volume reductions in the peri-Sylvian regions (e.g., superior temporal gyrus and insula), which are related to positive psychotic symptoms, progress around the onset (critical stage) of schizophrenia, but become stable in the chronic stage. On the other hand, morphological changes in the fronto-thalamic regions and lateral ventricle, which are related to negative symptoms, neurocognitive dysfunction, and the functional outcome, progress during both the critical and chronic stages. These changes in the peri-Sylvian and fronto-thalamic regions may provide a pathophysiological basis for Crow's two-syndrome classification. Accumulated evidence from early intervention trials suggests that the transition risk from an at-risk mental state (ARMS) to psychosis is approximately 30%. Differences in the cognitive performance, event-related potentials (e.g., mismatch negativity), and brain morphology have been reported between ARMS subjects who later developed psychosis and those who did not. Whether early intervention for ARMS significantly improves the long-term recovery rate of schizophrenia patients remains unknown. With respect to the development of novel therapeutics, animal models of schizophrenia based on the
-methyl-d-aspartate receptor hypofunction hypothesis successfully mimicked behavioral changes associated with cognitive impairments characteristic of the disease. Furthermore, these animal models elicited histological changes in the brain similar to those observed in schizophrenia patients, i.e., decreased numbers of parvalbumin-positive interneurons and dendritic spines of pyramidal neurons in the frontal cortex. Some antioxidant compounds were found to ameliorate these behavioral and histological abnormalities.
Early intervention coupled with novel therapeutics may offer a promising approach for substantial improvement of the functional outcome of schizophrenia patients.
An increased prevalence of duplicated Heschl’s gyrus (HG) has been repeatedly demonstrated in various stages of schizophrenia as a potential neurodevelopmental marker, but it remains unknown whether ...other neuropsychiatric disorders also exhibit this macroscopic brain feature. The present magnetic resonance imaging study aimed to examine the disease specificity of the established finding of altered HG patterns in schizophrenia by examining independent cohorts of bipolar disorder (BD) and major depressive disorder (MDD). Twenty-six BD patients had a significantly higher prevalence of HG duplication bilaterally compared to 24 age- and sex-matched controls, while their clinical characteristics (e.g., onset age, number of episodes, and medication) did not relate to HG patterns. No significant difference was found for the HG patterns between 56 MDD patients and 33 age- and sex-matched controls, but the patients with a single HG were characterized by more severe depressive/anxiety symptoms compared to those with a duplicated HG. Thus, in keeping with previous findings, the present study suggests that neurodevelopmental pathology associated with gyral formation of the HG during the late gestation period partly overlaps between schizophrenia and BD, but that HG patterns may make a somewhat distinct contribution to the phenomenology of MDD.
Inter-individual variations in the sulco-gyral pattern of Heschl’s gyrus (HG) might contribute to emotional processing. However, it remains largely unknown whether borderline personality disorder ...(BPD) patients exhibit an altered HG gyrification pattern, compared with healthy individuals, and whether such a brain morphological feature, if present, might contribute to their clinical characteristics. The present study used magnetic resonance imaging to investigate the distribution of HG gyrification patterns (single or duplicated) and their relationship to clinical characteristics in teenage BPD patients with minimal treatment exposure. No significant difference was noted for the prevalence of HG patterns between 20 BPD and 20 healthy participants. However, the BPD participants with left duplicated HG were characterized by higher prevalence of comorbid disruptive behavior disorders, with higher externalizing score compared with those with left single HG. Our preliminary results suggest that neurodevelopmental pathology associated with gyral formation might be implicated in the neurobiology of early BPD, especially for emotional and behavioral control.
Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the ...pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.
HLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.
The predisposing association of DRB1*04:01 (P = 0.0006, corrected P Pc = 0.0193, odds ratio OR 2.97, 95% confidence interval CI 1.62-5.43), DRB1*04:05 (P = 1.89×10-21, Pc = 5.86×10-20, OR 3.41, 95% CI 2.65-4.38), and DQB1*04:01 (P = 4.66×10-18, Pc = 6.99×10-17, OR 3.89, 95% CI 2.84-5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32-0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10-9, OR 3.52, 95% CI 2.34-5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45-424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10-6, OR 10.64, 95% CI 3.19-35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.
The important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes.
Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in ...glomerulosclerosis using the podocyte-specific injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and aberrant endothelial PAI-1 protein already on day 1, before thrombosis and proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and preserved podocyte numbers in NEP25/LMB2 mice by stabilization of β1-integrin translocation. Heparin loading significantly reduced thrombotic formation, whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody failed to cause detachment. Confocal microscopy and cell surface biotinylation experiments showed that internalized β1-integrin was found together with uPAR in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking antibody protected cultured podocytes from cell detachment. In conclusion, PAI-1/uPA complex-mediated uPAR-dependent podocyte β1-integrin endocytosis represents a novel mechanism of glomerular injury leading to progressive podocytopenia. This aberrant cross-talk between podocytes and endothelial cells represents a feedforward injury response driving podocyte loss and progressive glomerulosclerosis.
Abstract
Background
We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to ...evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018.
Methods
The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018.
Results
NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%:
P
= 0.008), hypertension (48.5–57.4%:
P
= 0.047), and hyperlipidemia (39.2–53.8%:
P
= 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61:
P
= 0.026) and the median platelet count increased (15.1–17.9 × 10
4
/μL:
P
= 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (
P
< 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC.
Conclusions
The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.
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