Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes.We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.
Adult ; Animals ; Autistic Disorder ; Blood-Brain Barrier ; Cell Death ; Cerebrospinal Fluid ; Grooming ; Humans ; Injections, Intraperitoneal ; Mass Screening ; Mice ; Mice, Inbred ICR ; N-Methylaspartate ; Neurons ; Nociception ; Pathology ; Synaptic Transmission ; Tail

Ovarian cancer is one of the leading causes of cancer-related deaths in gynecological malignancies. Over 70% of ovarian cancer cases are high-grade serous ovarian cancers and have high death rates due to their resistance to chemotherapy. Despite advances in surgical and pharmaceutical therapies, overall survival rates are not good, and making an accurate prediction of the prognosis is not easy because of the highly heterogeneous nature of ovarian cancer. To improve the patient's prognosis through proper treatment, we present a prognostic prediction model by integrating high-dimensional RNA sequencing data with their clinical data through the following steps: gene filtration, pre-screening, gene marker selection, integrated study of selected gene markers and prediction model building. These steps of the prognostic prediction model can be applied to other types of cancer besides ovarian cancer.
Drug Therapy ; Filtration ; Mortality ; Ovarian Neoplasms ; Prognosis ; RNA ; Sequence Analysis, RNA ; Survival Rate

PURPOSE: This study investigated the impact of subclinical borderline changes on the development of chronic allograft injury in patients using a modern immunosuppression protocol. METHODS: Seventy patients with stable renal allograft function and who underwent protocol biopsies at implantation, 10 days and 1 year after transplantation were included and classified based on biopsy findings at day 10. The no rejection (NR) group included 33 patients with no acute rejection. The treatment (Tx) group included 21 patients with borderline changes following steroid pulse therapy, and the nontreatment (NTx) group included 16 patients with borderline changes nontreated. RESULTS: The Banff Chronicity Score (BChS) and modified BChS (MBChS) were not different among the three groups at implantation (P = 0.48) or on day 10 (P = 0.96). Surprisingly, the NTx group had more prominent chronic scores at the 1-year biopsy, including BChS (3.07 +/- 1.33, P = 0.005) and MBChS (3.14 +/- 1.41, P = 0.008) than those in the Tx and NR group, and deterioration of BChS was more noticeable in the NTx group (P = 0.037), although renal function was stable (P = 0.66). No difference in chronic injury scores was observed between the Tx and NR groups at the 1-year biopsy. CONCLUSION: Subclinical borderline changes can be a risk factor for chronic allograft injury and should be considered for antirejection therapy.
Biopsy ; Cyclohexylamines ; Humans ; Immunosuppression ; Kidney ; Kidney Transplantation ; Rejection (Psychology) ; Risk Factors ; Transplantation, Homologous ; Transplants

This study was designed to compare the hospital-related costs of elective abdominal aortic aneurysm (AAA) treatment and cost structure between endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in Korean health care system. One hundred five primary elective AAA repairs (79 OSRs and 26 EVARs) performed in the Seoul National University Hospital from 2005 to 2009 were included. Patient characteristics were similar between two groups except for older age (P = 0.004) and more frequent history of malignancy (P = 0.031) in EVAR group. Thirty-day mortality rate was similar between two groups and there was no AAA-related mortality in both groups for 5 yr after repair. The total in-hospital costs for the index admission were significantly higher in EVAR patients (mean, KRW19,857,119) than OSR patients (mean KRW12,395,507) (P < 0.001). The reimbursement was also significantly higher in EVAR patients than OSR patients (mean, KRW14,071,081 vs KRW6,238,895, P < 0.001) while patients payments was comparable between two groups. EVAR patients showed higher follow-up cost up to 2 yr due to more frequent imaging studies and reinterventions for type II endoleaks (15.4%). In the perspective of cost-effectiveness, this study suggests that the determination of which method to be used in AAA treatment be more finely trimmed and be individualized.
Aged ; Aged, 80 and over ; Aortic Aneurysm, Abdominal/economics/mortality/*surgery ; Blood Vessel Prosthesis Implantation/*economics ; Cost-Benefit Analysis ; Endoleak ; Female ; Follow-Up Studies ; Humans ; Insurance, Health, Reimbursement ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Republic of Korea ; Survival Analysis ; Treatment Outcome ; Vascular Surgical Procedures/*economics

BACKGROUND: Several studies reported that sub-clinical rejection (SCR) detected by a protocol biopsy soon after renal transplantation does permanent damage to a renal allograft, contributing to chronic allograft nephropathy (CAN). This article investigated the risk factors involved in SCR and the effects of treating SCR, and evaluated the clinical significance of a protocol biopsy soon after renal transplantation. METHODS: From January 2007 to June 2010, 253 patients received renal transplantation. Patients were divided into two groups according to whether or not they had undergone a protocol biopsy. To analyze the effect of SCR treatments, patients who were diagnosed with SCR were divided into two groups according to whether or not they had been treated with SCR. The patients who did not undertake a protocol biopsy were included in the untreated groups. RESULTS: Among 138 patients who undertook protocol biopsies, 65 patients (47.1%) showed SCR. In univariate analysis, both the number of HLA-DR mismatches (P=0.003) and not using Simulect (P=0.01) were identified as risk factors of SCR. In multivariate analysis, not using Simulect (P=0.006) was identified as an risk factor independent of SCR. deltaGFR, subtracting GFR at 1 week from GFR at that point, showed significant differences between SCR-treated patients and untreated patients at 1, 3, 6, 9, 12, 24, and 36 months with a P value of less than 0.05. CONCLUSIONS: A protocol biopsy can detect SCR, especially in patients with risk factors such as a high number of HLA mismatches or not using Simulect. Treatment of SCR detected by protocol biopsy will help to improve long-term renal function.
Antibodies, Monoclonal ; Biopsy ; HLA-DR Antigens ; Humans ; Kidney Transplantation ; Multivariate Analysis ; Recombinant Fusion Proteins ; Rejection (Psychology) ; Risk Factors ; Transplantation, Homologous

BACKGROUND: Several studies reported that sub-clinical rejection (SCR) detected by a protocol biopsy soon after renal transplantation does permanent damage to a renal allograft, contributing to chronic allograft nephropathy (CAN). This article investigated the risk factors involved in SCR and the effects of treating SCR, and evaluated the clinical significance of a protocol biopsy soon after renal transplantation. METHODS: From January 2007 to June 2010, 253 patients received renal transplantation. Patients were divided into two groups according to whether or not they had undergone a protocol biopsy. To analyze the effect of SCR treatments, patients who were diagnosed with SCR were divided into two groups according to whether or not they had been treated with SCR. The patients who did not undertake a protocol biopsy were included in the untreated groups. RESULTS: Among 138 patients who undertook protocol biopsies, 65 patients (47.1%) showed SCR. In univariate analysis, both the number of HLA-DR mismatches (P=0.003) and not using Simulect (P=0.01) were identified as risk factors of SCR. In multivariate analysis, not using Simulect (P=0.006) was identified as an risk factor independent of SCR. deltaGFR, subtracting GFR at 1 week from GFR at that point, showed significant differences between SCR-treated patients and untreated patients at 1, 3, 6, 9, 12, 24, and 36 months with a P value of less than 0.05. CONCLUSIONS: A protocol biopsy can detect SCR, especially in patients with risk factors such as a high number of HLA mismatches or not using Simulect. Treatment of SCR detected by protocol biopsy will help to improve long-term renal function.
Antibodies, Monoclonal ; Biopsy ; HLA-DR Antigens ; Humans ; Kidney Transplantation ; Multivariate Analysis ; Recombinant Fusion Proteins ; Rejection (Psychology) ; Risk Factors ; Transplantation, Homologous

Hemodialysis access-related arterial steal syndrome can result in serious complications, such as tissue loss and amputation. Several methods have been used to treat arterial steal syndrome, but controversy persists regarding the optimal technique. Here we present a case of arterial steal syndrome successfully treated with proximalization of arterial inflow (PAI). A 63-year-old man with a brachial-cephalic arteriovenous fistula (AVF) was admitted with complaints of coldness and pain in the left hand and fingers. Duplex sonography and angiography revealed arterial steal and occlusion of the distal radial artery. He was underwent PAI which included transsection of the AVF just distal to the previous anastomosis and attachment of the arterialized vein to a more proximal portion of the brachial artery with a 4-mm expanded polytetrafluoroethylene graft. Digital arterial flow was restored, and his symptoms subsequently were relieved. The AVF was well-functioning without any ischemic symptoms after 3-month follow-up.
Amputation ; Angiography ; Arteriovenous Fistula ; Brachial Artery ; Cold Temperature ; Fingers ; Follow-Up Studies ; Hand ; Humans ; Middle Aged ; Polytetrafluoroethylene ; Radial Artery ; Renal Dialysis ; Transplants ; Veins

PURPOSE: In this multi institutional study, the data of 604 men with clinically localized prostate cancer, who underwent radical prostatectomy, with updated nomograms predicting the pathological stage, were analyzed. MATERIALS AND METHODS: Prostate biopsies and prostatectomy specimens from men treated with radical prostatectomy, obtained between 1990 and 2003, were included. The patient distribution with respect to clinical stage, serum prostate-specific antigen (PSA) and biopsy Gleason score, as well as final pathological findings, including organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node metastasis (LNM), were analyzed for the construction of nomograms representing the percent probabilities of each respective pathological outcome. RESULTS: The median serum PSA at the time of surgery and biopsy Gleason score were 9.9ng/ml and 7, respectively. The preoperative serum PSA was 4ng/ml or less in 38 (6.3%) patients and the tumor was impalpable in 292 (48.2%) of patients. The biopsy Gleason scores were 7 and 8 or higher in 186 (30.7%) and 169 (27.9%), respectively. Throughout the clinical stages and PSA ranges, the Gleason score was 7 or higher in more than 50% of patients, but 8-10 in 20-30%. The overall OCD, ECE, SVI and LNM rates were 57.1, 27.8, 10.9 and 4.2%, respectively. CONCLISIONS: A significantly high proportion of prostate cancers arising in Korean men exhibited poor differentiation, with Gleason scores of 7 or higher, regardless of the clinical stage or initial serum PSA. Updated nomograms acknowledging such characteristics have been developed, which may aid in the treatment planning of these individuals.
Biopsy ; Humans ; Lymph Nodes ; Male ; Neoplasm Grading ; Neoplasm Metastasis ; Nomograms* ; Prostate* ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms* ; Seminal Vesicles