Predictive accuracy of a health risk appraisal program using mortality risk age in 116,927 Korean men

Health risk appraisal (HRA) is a tool for determining health risk factors and motivating individuals to maintain a healthy lifestyle. We performed this study to describe the HRA algorithm and evaluate the accuracy of an HRA program for 10-yr mortality prediction in Korean men. We used data derived from periodic health examinations of 116,927 male public officials and school personnel aged 20 or older. Risk age and the difference between risk age and calendar age were calculated. We obtained the hazard ratio (HR) of 10-yr mortality according to the calculated age difference. Of the 116,927 subjects, 1,900 (1.6%) died during the 10 yr after the 1992 medical examinations. The HR of 10-yr mortality increased significantly with age difference. Compared with the HR in the reference group (age difference below 2 yr), the HR in the group with a 2- to 6-yr age difference was 1.20 (95% confidence interval [CI]: 1.05 to 1.38) and HR in the group with more than 7-yr age difference was 1.35 (95% CI: 1.14 to 1.75). Risk age is a relatively good predictor of 10-yr mortality in Korean men and may be useful in identifying high-risk middle-aged men for health interventions.     

Therapy-related myelodysplastic syndrome/acute myeloid leukemia with del(7)(q22) in a patient with de novo AML

A 55-year-old Korean woman was initially diagnosed with acute myelomonocytic leukemia (AML). After induction chemotherapy was performed using cytarabine, idarubicin, and G-CSF, complete remission (CR) was subsequently achieved following reinduction chemotherapy using the same chemotherapeutic agents. Thirty-six months after the initial CR, an increase in immature cells (up to 12.0%) was observed in the patient's bone marrow. Because chromosome analysis revealed a karyotype of 46,XX,del(7)(q22) in all of the analyzed cells, the patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Although the patient subsequently received chemotherapy and G-CSF for neutropenia, t-MDS rapidly progressed after 3 months to therapy-related acute myeloid leukemia (t-AML). Although very rare, de novo AML can progress to a secondary MDS/AML with del(7q) after chemotherapy with cytarabine, idarubicin, and G-CSF. Further investigation into the role of genes located in 7q22 may provide more information about the mechanisms of leukemogenesis.     

DNA methylation profile during multistage progression of pulmonary adenocarcinomas

Multiple genetic and epigenetic alterations are known to be involved in the carcinogenesis of peripheral pulmonary adenocarcinoma (ADC). However, epigenetic abnormalities have not been extensively investigated in the following multistage progression sequence: atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to invasive ADC. To determine the potential role of promoter methylation during ADC development of the lung, we examined methylation status in 20 normal, 20 AAH, 30 AIS, and 60 ADC lung tissues and compared methylation status among the lesions. The MethyLight assay was used to determine the methylation status of 18 CpG island loci, which were hypermethylated in ADC compared to noncancerous lung tissues. The mean number of methylated CpG island loci was significantly higher in ADC than in AAH and AIS, (p < 0.003 between ADC and AAH, p < 0.005 between ADC and AIS). Aberrant methylation of HOXA1, TMEFF2, and RARB was frequently observed in preinvasive lesions, including AAH and AIS. Furthermore, methylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was significantly more frequent in invasive ADC than AAH or AIS. Our results indicate that epigenetic alterations are involved in the multistep progression of pulmonary ADC development, and aberrant CpG island methylation accumulates during multistep carcinogenesis. In addition, aberrant methylation of HOXA1, TMEFF2, and RARB occurred in preinvasive lesions, which indicates that epigenetic alterations of these genes are involved in the early stages of pulmonary ADC development. In contrast, hypermethylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was more frequent in invasive ADC than in preinvasive lesions, which indicates that methylation of these genes occurs later during tumor invasion in the AAH–AIS–ADC sequence.     

Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC) class I expression by increasing interferon-gamma (IFN-gamma)

Tumor immunity is primarily mediated by cells as CD8+ cytotoxic T lymphocytes (CTL) recognize tumor antigen by MHC class I molecules. But most tumors are associated with a decreased expression of MHC class I to escape the antitumor immunity of the host. Our previous data have demonstrated that MPL has an antitumor effect on metastatic lung cancer of B16 melanoma with enhancing cytotoxicity due to increase of IFN-gamma and IL-2, and decrease of IL-4, which indicates the stimulation of type 1 helper T cells (Th1). To determine the effects of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha on MHC class I expression of B16 melanoma cells, we evaluated the expression of MHC class I molecules with treatments of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha by flow cytometry. The supernatant of MPL-treated spleen cells in vitro upregulated the expression of MHC class I molecules of B16 melanoma cells compared to the control supernatant of spleen cells. The MHC class I expression of B16 melanoma cells treated with IFN-gamma, but not TNF-alpha or IL-1 alpha, increased in a time-dependent manner. In conclusion, MPL upregulated MHC class I expression of B16 melanoma cells by activating spleen cells via IFN-gamma. These data suggest that increased IFN-gamma by MPL is responsible for the upregulation of MHC class I expression to augment cytotoxicity. Therefore, we suggest that MPL could play an important role in immunotherapy.     

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome

BackgroundThe mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS.MethodsThe RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls.ResultsPatients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered.ConclusionThe patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Deformation-induced ω phase in modified Ti–29Nb–13Ta–4.6Zr alloy by Cr addition

For spinal-fixation applications, implants should have a high Young’s modulus to reduce springback during operations, though a low Young’s modulus is required to prevent stress shielding for patients after surgeries. In the present study, Ti–29Nb–13Ta–4.6Zr alloy (TNTZ) with a low Young’s modulus was modified by adding Cr to obtain a higher deformation-induced Young’s modulus in order to satisfy these contradictory requirements. Two newly designed alloys, TNTZ–8Ti–2Cr and TNTZ–16Ti–4Cr, possess more stable β phases than TNTZ. These alloys consist of single β phases and exhibit relatively low Young’s moduli of <65 GPa after solution treatment. However, after cold rolling, they exhibit higher Young’s moduli owing to a deformation-induced ω-phase transformation. These modified TNTZ alloys show significantly less springback than the original TNTZ alloy based on tensile and bending loading–unloading tests. Thus, the Cr-added TNTZ alloys are beneficial for spinal-fixation applications.     

Procalcitonin Levels in Patients with Complete and Incomplete Kawasaki Disease

Incomplete Kawasaki disease (iKD) is considered to be a less complete form of Kawasaki disease (cKD), and several differences in the laboratory presentations of iKD and cKD have been noted. We investigated serum procalcitonin levels in patients with iKD, cKD, and other febrile diseases (a control group). Seventy-seven patients with cKD, 24 with iKD, and 41 controls admitted to our hospital from November 2009 to November 2011 were enrolled in the present study. We obtained four measurements of serum procalcitonin levels and those of other inflammatory markers from each patient. Samples were taken for analysis on the day of diagnosis (thus before treatment commenced; D0) and 2 (D2), 14 (D14), and 56 days (D56) after intravenous immunoglobulin infusion. We obtained control group data at D0. The mean D0 serum procalcitonin levels of cKD patients (0.71 ± 1.36 ng/mL) and controls (0.67 ± 1.06 ng/mL) were significantly higher than those of iKD patients (0.26 ± 0.26 ng/mL) (P = 0.014 and P = 0.041, resp.). No significant difference in mean procalcitonin level was evident among groups at any subsequent time. In conclusion, the serum procalcitonin level of patients with acute-stage cKD was significantly higher than that of iKD patients.     

Brain injury-associated biomarkers of TGF-beta1, S100B,GFAP, NF-L,tTG, AbetaPP,and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by <Emphasis Type="Italic">Toxocara canis</Emphasis>in mice

Background  

Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor β1 (TGF-β1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), β-amyloid precursor proteins (AβPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT.