Objective: To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. Methods: This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. Results: The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p ＜ 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71−100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p＜ 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p＜ 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p ＜ 0.001; McNemar-Bowker test). Conclusion Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Background/Aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. Methods: This retrospective multinational study involved multiple centers in Korea, China, Tai-wan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form. Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. Conclusions Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

INTRODUCTION: We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore. METHODS: Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004). RESULTS: Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January-July 2019, to 274 per day in January-July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January-July 2019 (19,629) to January-July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January-July 2019 and 21% in January-July 2020. CONCLUSION Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally.
Adolescent ; COVID-19/prevention & control* ; Child ; Child, Preschool ; Disease Outbreaks ; Emergency Service, Hospital/trends* ; Facilities and Services Utilization/trends* ; Female ; Health Policy ; Humans ; Infant ; Infant, Newborn ; Male ; Patient Acceptance of Health Care/statistics & numerical data* ; Patient Admission/trends* ; Pediatrics ; Retrospective Studies ; Severe Acute Respiratory Syndrome/epidemiology* ; Singapore/epidemiology*

INTRODUCTION: Child sexual abuse (CSA) adversely affects a child's growth and well-being. This study aimed to describe the profile of children presenting to a tertiary paediatric emergency department(ED) with CSA. METHODS: Children 0-16 years old presenting to KK Women's and Children's Hospital ED from June 2016 to August 2020 with sexual abuse were retrospectively reviewed. We performed a secondary analysis on girls and stratified them by age <13 and ≥13 years old. RESULTS: There were 790 patients who made 833 visits for CSA. Victims were predominantly girls (747, 94.8%) and perpetrators were predominantly men (763, 96.6%). The abuse first occurred before the age of 13 years in 315 victims (39.9%). For 468 (59.2%), more than one incident occurred before presentation. Compared to girls ≥13 years old, girls <13 years old were more frequently abused by a family member (47.7% versus 8.0%, CONCLUSION The findings highlight common characteristics of CSA cases, and can aid the future identification and protection of vulnerable children. The fact that most children presented after more than one incident suggests the need to more closely monitor and protect potentially at-risk children.
Adolescent ; Child ; Child Abuse ; Child Abuse, Sexual ; Child, Preschool ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Parents ; Retrospective Studies

Syphilis, along with the recent increase of human immunodeficiency virus (HIV) patients, has also been on the rise. It has a broad spectrum of clinical manifestations, among which cerebral gumma is, a kind of neurosyphilis, however, it is rare and can be cured by penicillin. Thus, cerebral gumma needs to be differentially diagnosed from other brain masses that may be present in syphilis patients. We have experienced a case where the patient was first suspected of brain tumor, but confirmed by surgery to be cerebral gumma due to neurosyphilis. This is the first such case encountered in Korea, therefore, we report it here in. A 40-year old woman complaining of headaches was found to have a brain mass on her CT scans and MRI. Suspecting a brain Tumor, a resection was performed on the patient, and histological results revealed that the central portion of the mass contained necrotic material and the peripheral region was infiltrated with plasma cells. Warthin-Starry staining of the region revealed spirochetes, and the patient was thus diagnosed as brain gumma. Venereal Disease Research Laboratory (VDRL) of cerebrospinal fluid (CSF) was reactive. After an operation, penicillin-G at a daily dose of 24x10(6) U was given for 10 days from post-operative day 10, and thereafter, the mass disappeared.
Adult ; Brain Neoplasms/*diagnosis/pathology/radiography ; Female ; HIV Infections/*diagnosis/radiography ; Humans ; Magnetic Resonance Imaging ; Neurosyphilis/*diagnosis/pathology/radiography ; Tomography, X-Ray Computed

BACKGROUND AND OBJECTIVES: Granulocytes-colony stimulating factor (G-CSF) has a stem cell mobilizing capacity and favorable effects on ventricular remodeling following a myocardial infarction. G-CSF based stem cell therapy has shown favorable results in animal studies. However, the long term outcome of G-CSF based stem cell therapy in clinical trial remains unknown. Herein, we report the six month follow up results of two different G-CSF based stem cell therapy strategies. SUBJECTS AND METHODS: We compared the intra-coronary infusion of mobilized peripheral blood stem cells (PBSCs) with G-CSF (n=10), mobilization with G-CSF alone (n=16) and control percutaneous coronary intervention (PCI) alone (n=15) in patients following a myocardial infarction. RESULTS: At the six month follow up evaluations, the intra-coronary cell infusion was found to have improved the left ventricular (LV) systolic function and remodeling compared to the baseline, whereas G-CSF alone showed no improvement. Therefore, an intra-coronary cell infusion showed better improvements in the LV systolic function (p<0.001) and remodeling (p<0.01) than G-CSF alone. Cell infusion also showed better results than the control PCI alone group, but these did not reach statistical significance with the limited number of patients used in this study. Patients who received G-CSF administration showed a modest increase of binary restenosis (p=0.185) and a greater late loss in the minimal luminal diameter at the 6 month follow up than the control group. CONCLUSION: An intra-coronary cell infusion of mobilized PBSCs using G-CSF was found to be better than G-CSF alone at the six month follow up evaluation. G-CSF was also found to increase the potential risk of restenosis, especially when administered prior to stent implantation. The efficacy of an intra-coronary infusion of mobilized PBSCs should be evaluated in a large randomized controlled trial.
Animals ; Coronary Restenosis ; Follow-Up Studies* ; Granulocyte Colony-Stimulating Factor ; Humans ; Magic* ; Myocardial Infarction* ; Percutaneous Coronary Intervention ; Phenobarbital ; Stem Cells* ; Stents ; Ventricular Remodeling

NF-kappa B promotes cell survival against external stress such as radiation. We examined whether NF-kappa B decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappa B p65 in VSMCs was confirmed by immunofluorescence. NF-kB decoy transfection resulted in inhibition of the radiation-induced NF-kB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappa B. By using MTT assay, NF-kappa B decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappa B decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappa B inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappa B decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappa B decoy transfection, P < 0.05). In addition, at 48 h, NF-kappa B decoy transfection dose dependently (10 mM vs. 20 mM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 mM sulfasalazine, a specific NF-kappa B inhibitor. These results indicate that NF-kappa B inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappa B decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.
Animals ; Aorta/cytology/radiation effects ; *Apoptosis ; Cell Cycle/physiology/radiation effects ; Cell Proliferation/radiation effects ; Cells, Cultured ; Gamma Rays ; Intercellular Adhesion Molecule-1/metabolism ; Male ; Muscle, Smooth, Vascular/cytology/physiology/*radiation effects ; Myocytes, Smooth Muscle/cytology/radiation effects ; NF-kappa B/*antagonists & inhibitors/metabolism ; Nitric-Oxide Synthase/metabolism ; Protein Transport ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't ; Transcription, Genetic ; Transfection ; Tumor Necrosis Factor-alpha/metabolism

BACKGROUND AND OBJECTIVES: Oxidative stress plays an important role in the pathogenesis of coronary atherosclerosis and spasm. We investigated whether the polymorphisms in two oxidative stress-related genes, paraoxonase and p22phox, are associated with risks of coronary artery spasm and stenosis. SUBJECTS AND METHODS: The study comprised of 116 patients with variant angina, 118 patients with coronary artery stenosis and 117 control subjects, who were all classified by coronary angiography. In all three groups, the genotype frequencies of the Q192R polymorphism of the paraoxonase gene and C242T polymorphism of the p22phox gene were analyzed, and the serum thiobarbituric acid-reactive substance concentrations measured. RESULTS: The frequency of the RR genotype of the paraoxonase Q192R polymorphism was significantly higher in patients with variant angina and coronary artery stenosis than in the control subjects (40.4% in variant angina and 37.8% in coronary artery stenosis vs. 24.7% in control, p=0.020 and 0.048, respectively). From the multivariate analysis, the odds ratio of the RR genotype was 2.240 for variant angina (95% confidence interval ; 1.012-4.956), and 2.333 for coronary artery stenosis (95% confidence interval ; 1.140-4.777), in relation to the control subjects. The thiobarbituric acid-reactive substance level was significantly higher in the RR type than in the QQ+QR types (RR vs. QQ+QR : 1.106+/-0.420 nmol/mL vs. 0.949+/-0.311 nmol/mL, p=0.028). There was no significant difference in the prevalence of the C242T polymorphism of the p22phox gene between the three groups. CONCLUSION: The RR genotype of the paraoxonase gene Q192R polymorphism was found to be an independent risk factor for both coronary spasm and stenosis.
Angina Pectoris ; Aryldialkylphosphatase* ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis* ; Coronary Vessels* ; Genotype ; Humans ; Multivariate Analysis ; Odds Ratio ; Oxidative Stress* ; Polymorphism, Single Nucleotide ; Prevalence ; Risk Factors ; Spasm

BACKGROUND AND OBJECTIVES: The 5-HT2A receptor is one of the main mediators of a serotonin-evoked coronary artery contraction. This is because vasoconstriction is selectively blocked by the 5-HT2 receptor antagonist, with the 5-HT2A receptor gene mRNA being detected in spastic coronary arteries. The relationship between the T102C polymorphism of the 5-HT2A receptor gene and the response to the 5-HT2A antagonist (clozapine) has recently been established, suggestive of a functional implication. Previous studies have observed an association between low cholesterol levels and mental disorders, but the underlying cause has not been determined. It has been established that the T102C polymorphism of the 5-HT2A serotonin receptor gene and a variety of psychological problems are related, but the relationship between the serum lipid level and this genetic polymorphism has not been reported. We investigated the influence of this polymorphism on coronary artery disease, including vasospastic angina and the clinical parameters, such as the lipid profile. SUBJECTS AND METHODS: After a diagnostic angiography was performed, the genotype was identified from the genomic DNA extracted from the peripheral blood of 646 patients without specific psychiatric diseases. RESULTS: There were no differences in the genotype frequencies between coronary artery disease, coronary artery disease with vasospasm, and the normal control groups, even from a subgroup analysis of the clinical parameters. Contrary to previous reports, the genotype distribution was not related to a myocardial infarction or hypertension. The lipid profile analysis showed significantly lower total cholesterol (193.5 vs. 202.1mg/dL, p=0.016) and HDL-cholesterol (42.7 vs. 46.2mg/dL, p=0.003) levels in the CC genotype than the other genotypes, and the frequencies of CC genotype showed a significantly decreasing trend between the HDL-cholesterol (p=0.003) and total cholesterol (p=0.003) quartiles. From a multivariate analysis, only the HDL-cholesterol level was significantly associated with a lower frequency of the CC genotype (p=0.006). CONCLUSION: The T102C polymorphism is not related to coronary artery disease, including vasospasm of the coronary artery, but the CC genotype of this polymorphism is related to low HDL-cholesterol. We identified a novel genetic polymorphism of the serotonin receptor, which affects the HDL-cholesterol level. Because previous observational studies have shown an association between low cholesterol levels and mental disorders, our data should be considered when analyzing the serum lipid levels and serotonin receptor function in humans.
Angiography ; Cholesterol ; Coronary Artery Disease* ; Coronary Vessels* ; DNA ; Genotype ; Humans ; Hypertension ; Mental Disorders ; Multivariate Analysis ; Muscle Spasticity ; Myocardial Infarction ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT2A* ; RNA, Messenger ; Serotonin ; Serotonin 5-HT2 Receptor Antagonists ; Vasoconstriction

Focal segmental glomerulosclerosis (FSGS) is presented as not only one of the primary glomerular diseases but also as a secondary phenomenon for chronic irreversible renal diseases. The main pathological feature of FSGS is the accumulation of extracellular matrix in the glomeruli, for which overexpression of transforming growth factor-beta (TGF-beta) may be responsible for the accumulation of pathological matrix. A new animal model (FGS/NgaKist mouse) of renal failure by spontaneously generating glomerulosclerosis was developed. To elucidate the role of TGF-beta for FSGS, authors observed glomeruli of FGS/NgaKist mouse periodically. FGS/NgaKist mouse strain showed progression of proteinuria and focal glomerular sclerosis with the aging. The glomeruli showed anti IgG, IgA, IgM and complement complex deposits and extracellular matrix accumulation in the mesangium. TGF-beta mRNA and beta2antibody expressions were increased with the advance of glomerular sclerosis. The results suggest the following; FSGS of FGS/NgaKist strain is immune mediated disease and this stimuli on mesangial or endothelial cells may activate TGF-beta gene in their nuclei. This activation, in turn, can cause sclerosis by increasing TGF-beta mRNA transcription followed by secretion of TGF-beta and its action as cytokine for making collagen fibrils.
Aging ; Animals ; Collagen ; Complement System Proteins ; Endothelial Cells ; Extracellular Matrix ; Glomerulosclerosis, Focal Segmental ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Mice* ; Models, Animal ; Proteinuria ; Renal Insufficiency ; RNA, Messenger ; Sclerosis ; Transforming Growth Factor beta