Influence of Age and Sex on Post-Craniotomy Headache.

Post-craniotomy headache (PCH) is a common postoperative complication, and some of these patients progress to chronic PCH (CPCH). We aimed to identify clinical variables associated with PCH and its progression to CPCH, especially possible associations between age and sex differences. Therefore, we examined clinical information on PCH using the Clinical Data Warehouse over 10 years. Of the 1326 patients included, 927 patients (69.9%) experienced PCH. In multivariate analysis for PCH, age was inversely related to risk (p = 0.003), and being female showed a significant association with an increased risk of PCH (p = 0.002). There was also a significant inverse relationship between age and severity of the worst headache, with younger female patients reporting greater severity of the worst headache (p < 0.001). Of the 927 patients who experienced PCH, 319 (34.4%) progressed to CPCH. Sex was a significant factor, with females having a higher risk of developing CPCH compared to males (p < 0.001). In addition, the presence of preoperative headaches significantly increased the risk of CPCH (p = 0.001). The occurrence of PCH is associated with younger age and female sex. In particular, female sex and preoperative headaches increased the risk of developing CPCH. These clinical factors should be considered in patients undergoing neurosurgery.

Longitudinal Genome-Wide Association Study of Cognitive Impairment after Subarachnoid Hemorrhage.

OBJECTIVES: The occurrence of cognitive deficits after subarachnoid hemorrhage (SAH) is highly possible, leading to vascular dementia. We performed a novel longitudinal genome-wide association study (GWAS) to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study. MATERIALS AND METHODS: This GWAS involved 153 patients with SAH sharing 5,971,372 markers after high-throughput imputation. Genome-wide Cox proportional hazard regression testing was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined, based on GWAS-driven loci and risk stratification. RESULTS: Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five genome-wide signals, including rs138753053 (PDCD6IP-LOC101928135, HR = 28.33, p = 3.4 × 10-8), rs56823384 (LINC00499, HR = 12.47, p = 2.8 × 10-9), rs145397166 (CASC15, HR = 11.16, p = 1.7 × 10-8), rs10503670 (LPL-SLC18A1, HR = 2.88, p = 4.0 × 10-8), and rs76507772 (IRS2, HR = 5.99, p = 3.5 × 10-8), were significantly associated with cognitive impairment following SAH. In addition, the well-constructed wPRS containing five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667-0.824). Tertile stratification showed a higher effectiveness in predicting cognitive impairment, especially in those with haptoglobin 2-1 (HR = 44.59, 95% CI: 8.61-231.08). CONCLUSIONS: Our study revealed novel susceptible loci for cognitive impairment, longitudinally measured in patients with SAH. The clinical utility of these loci will be evaluated in further follow-up studies.

Therapeutic Effect of Donepezil on Neuroinflammation and Cognitive Impairment after Moderate Traumatic Brain Injury.

BACKGROUND: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil-an acetylcholinesterase (AChE) inhibitor-on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. METHODS: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 µM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. RESULTS: In vitro, donepezil was found to lead to increased cell viability and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1ß), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. CONCLUSIONS: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy.

Modeling of the brain-lung axis using organoids in traumatic brain injury: an updated review.

Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

N-Feruloylserotonin inhibits lipopolysaccharide-induced inflammation via SIRT1-stimulated FOXO1 and NF-κB signaling pathways in RAW 264.7 cells.

Macrophages become activated by a variety of stimuli such as lipopolysaccharide (LPS) and participate in the process of immune responses. Activated macrophages produce various inflammatory mediators. In the present study, we investigated the anti-inflammatory mechanism of a serotonin derivative, N-feruloylserotonin, isolated from safflower seeds in RAW 264.7 macrophages. N-Feruloylserotonin treatment significantly attenuated these effects on LPS-induced reactive oxygen species, nitric oxide, and prostaglandin E2 production in RAW 264.7 macrophages. Furthermore, N-feruloylserotonin significantly decreased the abnormal expression of mitogen-activated protein kinase, such as phosphor (p)-c-Jun N-terminal kinase and p-extracellular-signal regulated kinase activation. Further research revealed that N-feruloylserotonin could stimulate sirtuin1 (SIRT1), then promote the forkhead box protein O1 (FOXO1), and suppress nuclear factor-kappa B (NF-kB) signaling pathways. The present study suggests that N-feruloylserotonin may be a new anti-inflammatory component and a promising candidate for anti-inflammatory therapeutic agents through the regulation of SIRT1-stimulated FOXO1 and NF-kB signaling pathways.

Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease.

We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2-ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.

Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury.

BACKGROUND: We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available. METHODS: The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group). RESULTS: The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 ß were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1ß were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment. CONCLUSIONS: Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI.

Human embryonic stem cell-derived cerebral organoids for treatment of mild traumatic brain injury in a mouse model.

OBJECTIVE: There are no effective treatments for relieving neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated therapeutic efficacy of human embryonic stem cell-derived cerebral organoids (hCOs) in a mild TBI model, in terms of repair of damaged cortical regions, neurogenesis, and improved cognitive function. METHODS: Male C57BL/6 J mice were randomly divided into sham-operated, mild TBI, and mild TBI with hCO groups. hCOs cultured at 8 weeks were used for transplantation. Mice were sacrificed at 7 and 14 days after transplantation followed by immunofluorescence staining, cytokine profile microarray, and novel object recognition test. RESULTS: 8W-hCOs transplantation significantly reduced neuronal cell death, recovered microvessel density, and promoted neurogenesis in the ipsilateral subventricular zone and dentate gyrus of hippocampus after mild TBI. In addition, increased angiogenesis into the engrafted hCOs was observed. Microarray results of hCOs revealed neuronal differentiation potential and higher expression of early brain development proteins associated with neurogenesis, angiogenesis and extracellular matrix remodeling. Ultimately, 8W-hCO transplantation resulted in reconstruction of damaged cortex and improvement in cognitive function after mild TBI. CONCLUSION: hCO transplantation may be feasible for treating mild TBI-related neuronal dysfunction via reconstruction of damaged cortex and neurogenesis in the hippocampus.

Association of Haptoglobin Phenotypes with Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECT: We aimed to investigate the association of Haptoglobin (Hp) phenotypes with perihematomal edema (PHE) and neurological outcomes after intracerebral hemorrhage (ICH). METHODS: This prospective multicenter study enrolled patients that suffered ICH from March 2017 to February 2020. Hp phenotypes were determined using Western blotting; relative α1 intensity was calculated in patients with Hp2-1. A multivariable logistic regression analysis was then conducted to identify risk factors for increased relative PHE at 96 h and 3-month poor outcomes. RESULTS: In total, 120 patients were ultimately enrolled: Hp1-1 (n = 15, 12.5%); Hp2-1 (n = 51, 42.5%); and Hp2-2 (n = 54, 45.0%). Hp phenotype was significantly associated with PHE (p = 0.028). With Hp1-1 as a reference value, Hp2-2 significantly increased the likelihood of increased rPHE (OR = 6.294, 95% CI: 1.283-30.881), while Hp2-1 did not (OR = 2.843, 95% CI: 0.566-14.284). Poor outcomes were found to be closely associated with hematoma volume at admission (OR = 1.057, 95% CI: 1.015-1.101) and surgical treatment (OR = 5.340, 95% CI: 1.665-17.122) but not Hp phenotypes (p = 0.190). Further, a high level of relative α1 intensity was identified to be significantly associated with decreased rPHE (OR = 0.020, 95% CI: 0.001-0.358). However, the relative α1 intensity was not associated with poor outcomes (OR = 0.057, 95% CI: 0.001-11.790). CONCLUSIONS: ICH patients with Hp2-2 exhibited a higher likelihood of increased rPHE than those with Hp1-1. Higher relative α1 intensities were identified to be closely associated with rPHE in patients with Hp2-1.

Mild Traumatic Brain Injury and Subsequent Acute Pulmonary Inflammatory Response.

OBJECTIVE: The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. METHODS: Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. RESULTS: Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß were observed after mild TBI. The IL-6, TNF-α, and TGF-ß levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. CONCLUSION: Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.

Association of Haptoglobin Phenotype With Neurological and Cognitive Outcomes in Patients With Subarachnoid Hemorrhage.

Background: To assess the association of haptoglobin (Hp) phenotype with neurological and cognitive outcomes in a large cohort of patients with subarachnoid hemorrhage (SAH). Methods: This prospective multicenter study enrolled patients with aneurysmal SAH between May 2015 and September 2020. The Hp phenotype was confirmed via Western blots. The relative intensities of α1 in individuals carrying Hp2-1 were compared with those of albumin. Multivariable logistic and Cox proportional-hazard regression analyses were used to identify the risk factors for 6-month and long-term outcomes, respectively. Results: A total of 336 patients including the phenotypes Hp1-1 (n = 31, 9.2%), Hp2-1 (n = 126, 37.5%), and Hp2-2 (n = 179, 53.3%) were analyzed. The Hp phenotype was closely associated with 6-month outcome (p = 0.001) and cognitive function (p = 0.013), and long-term outcome (p = 0.002) and cognitive function (p < 0.001). Compared with Hp1-1 as the reference value, Hp2-2 significantly increased the risk of 6-month poor outcome (OR: 7.868, 95% CI: 1.764-35.093) and cognitive impairment (OR: 8.056, 95% CI: 1.020-63.616), and long-term poor outcome (HR: 5.802, 95% CI: 1.795-18.754) and cognitive impairment (HR: 7.434, 95% CI: 2.264-24.409). Long-term cognitive impairment based on the Hp phenotype was significantly higher in patients under 65 years of age (p < 0.001) and female gender (p < 0.001). A lower relative α1/albumin intensity (OR: 0.010, 95% CI: 0.000-0.522) was associated with poor outcome at 6 months but not cognitive impairment in patients with SAH expressing Hp2-1. Conclusion: Hp2-2 increased the risk of poor neurological outcomes and cognitive impairment compared with Hp1-1. For Hp2-1, higher relative α1 intensities were related to 6-month favorable outcomes.

Association Between Copeptin and Six-Month Neurologic Outcomes in Patients With Moderate Traumatic Brain Injury.

Background: Copeptin has been reported as a predictive biomarker for the prognosis after traumatic brain injury (TBI). However, most of them were in patients with severe TBI and limited value in predicting outcomes in patients with moderate TBI defined as Glasgow Coma Scale (GCS) score from 9 to 12. We aimed to investigate the predictive value of copeptin in assessing the neurologic outcome following moderate TBI. Methods: Patients were prospectively enrolled between May 2017 and November 2020. We consecutively measured plasma copeptin within 24 h after trauma, days 3, 5, and 7 using ELISA. The primary outcome was to correlate plasma copeptin levels with poor neurologic outcome at 6 months after moderate TBI. The secondary outcome was to compare the prognostic accuracy of copeptin and C-reactive protein (CRP) in assessing the outcome of patient. Results: A total of 70 patients were included for the final analysis. The results showed that 29 patients (41.4%) experienced a poor neurologic outcome at 6 months. Multivariable logistic regression analysis revealed that increased copeptin (odds ration [OR] = 1.020, 95% CI: 1.005-1.036), GCS score of 9 or 10 (OR = 4.507, 95% CI: 1.266-16.047), and significant abnormal findings on CT (OR = 4.770; 95% CI: 1.133-20.076) were independent risk factors for poor outcomes. Consecutive plasma copeptin levels were significantly different according to outcomes (p < 0.001). Copeptin on day 7 exhibited better prognostic performance than CRP with an area under receiver operating characteristic curve (AUROC) difference of 0.179 (95% CI: 0.032-0.325) in predicting 6-month poor outcomes. Conclusion: Plasma copeptin level can be a useful marker in predicting 6-month outcomes in patients with moderate TBI.

Acute respiratory symptoms and evacuation-related behavior after exposure to chlorine gas leakage.

BACKGROUND: A study was performed on the accidental chlorine gas leakage that occurred in a factory of printed circuit boards manufactured without chlorine. Health examination was performed for all 52 workers suspected of exposure to chlorine gas, and their evacuation-related behaviors were observed in addition to analyzing the factors that affected the duration of their acute respiratory symptoms. METHODS: Behavioral characteristics during the incidence of the accidental chlorine gas leakage, the estimated time of exposure, and the duration of subjective acute respiratory symptoms were investigated. In addition, clinical examination, chest radiography, and dental erosion test were performed. As variables that affected the duration of respiratory symptoms, dose group, body weight, age, sex, smoking, work period, and wearing a protective gear were included and analyzed by using the Cox proportional hazard model. RESULTS: Of 47 workers exposed to chlorine gas, 36 (77 %) developed more than one subjective symptom. The duration of the subjective symptoms according to exposure level significantly differed, with a median of 1 day (range, 0-5 days) in the low-exposure group and 2 days (range, 0-25 days) in the high-exposure group. Among the variables that affected the duration of the acute respiratory symptoms, which were analyzed by using the Cox proportional hazard model, only exposure level was significant (hazard ratio 2.087, 95 % CI = 1.119, 3.890). Regarding the evacuation-related behaviors, 22 workers (47 %) voluntarily evacuated to a safety zone immediately after recognizing the accidental exposure, but 25 workers (43 %) delayed evacuation until the start of mandatory evacuation (min 5, max 25 min). CONCLUSIONS: The duration of the subjective acute respiratory symptoms significantly differed between the low- and high-exposure groups. Among the 27 workers in the high-exposure group, 17 misjudged the toxicity after being aware of the gas leakage, which is a relatively high number.

Overlap syndrome with Sjögren's syndrome and systemic sclerosis in a steel rolling mill worker: a case report.

BACKGROUND: There are few reports about work-related factors associated with Sjögren's syndrome. We report a case of overlap syndrome with Sjögren's syndrome and systemic sclerosis. CASE PRESENTATION: A 54-year-old man was admitted due to dyspnea on exertion. The results of physical examination and laboratory findings were compatible with Sjögren's syndrome with systemic sclerosis. The patient had no pre-existing autoimmune disease, and denied family history of autoimmune disease. The patient worked in the large-scale rolling department of a steel manufacturing company for 25 years. Hot rolling is a rolling process performed at between 1100 °C and 1200 °C, generating a high temperature and a large amount of fumes, involving jet-spraying of water throughout the process to remove the instantaneously generated oxide film and prevent the high generation of fumes. In this process, workers could be exposed to silica produced by thermal oxidation. Other potential toxic substances including nickel and manganese seemed to be less likely associated with the patient's clinical manifestations. CONCLUSIONS: Occupational exposure to silica seemed to be associated with the patient's clinical manifestations of overlap syndrome with Sjögren's syndrome and systemic sclerosis. Although the underlying mechanism is still unclear, autoimmune disease including Sjögren's syndrome affects women more often than men and there was no family history of autoimmune disease. These suggested that there was an association between occupational silica exposure and the disease of the patient. Future research about the association between long-term low dose exposure to silica and the development of autoimmune diseases should be encouraged.

Higher Serum Heavy Metal May Be Related with Higher Serum gamma-Glutamyltransferase Concentration in Koreans: Analysis of the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1, 2, 2010, 2011).

BACKGROUND: Abnormal serum gamma-glutamyltransferase (γ-GT) may be an early and sensitive marker for oxidative stress. This study was performed to evaluate the association between serum heavy metals and γ-GT concentration. METHODS: This study is a cross-sectional analysis based on data from Korean National Health and Nutrition Examination Survey (V-1, 2, 2010, 2011) regarding serum heavy metal concentrations (lead, mercury, and cadmium) as well as serum γ-GT. Serum heavy metals were categorized into tertiles, and serum γ-GT concentration was compared using an analysis of covariance test after relevant variable adjustments. In addition, we evaluated the odds ratio (OR) of having the highest tertile of serum γ-GT in each heavy metal tertile using logistic regression. RESULTS: The mean serum lead, mercury, and cadmium concentrations were 2.67, 5.08, and 1.02 µg/dL in men and 1.95, 3.60, and 1.21 µg/dL in women, respectively. Partial correlation showed a significant positive relation between each heavy metal and serum γ-GT concentration. Comparing serum γ-GT concentration by the tertile of each heavy metal, serum γ-GT concentration showed a significant increase as the tertiles of serum mercury and cadmium in men and that of serum mercury in women increased, but not with lead. The OR of having the highest tertile of serum γ-GT was significant for cadmium in men (OR, 4.02; 95% confidence interval [CI], 2.54 to 6.35) and mercury in women (OR, 2.00; 95% CI, 1.29 to 3.10) in the top tertile of each heavy metal. CONCLUSION: Higher serum heavy metal concentration may be related with higher serum γ-GT concentration. In particular, serum cadmium in men and mercury in women showed significant correlation with serum γ-GT concentration.

The Relationship between Serum 25-Hydroxyvitamin D, Parathyroid Hormone and the Glomerular Filtration Rate in Korean Adults: The Korea National Health and Nutrition Examination Survey between 2009 and 2011.

BACKGROUND: The glomerular filtration rate (GFR) decreases with age, while parathyroid hormone (PTH) increases. There are a few reports only on the relationship between GFR and PTH under the category of serum 25-hydroxyvitamin D (25[OH]D) concentration. METHODS: Using the Korea National Health and Nutrition Examination Survey (KNHANES) data, a cross-sectional study was conducted on the association between serum 25(OH)D concentration, GFR and PTH in Korean adults aged 50 years or older. Serum PTH concentration was compared to the tertiles of GFR after adjustment for relevant variables. In addition, the serum PTH concentration was compared with the GFR under the category of serum 25(OH) D concentration (<20, 20-30, >30 ng/mL). RESULTS: The mean estimated GFR (eGFR) was 74.8 mL/min in men and 73.1 mL/min in women. The mean PTH and 25(OH) D was 66.8 pg/mL, 20.5 ng/mL in men and 69.0 pg/mL, 18.2 ng/mL in women. The serum PTH concentration showed a significant negative correlation with the serum 25(OH) D and eGFR in both genders. The serum PTH concentration significantly increased at the lower tertile of eGFR in male adults In addition, a decrease of serum PTH concentration was marked in the vitamin D sufficient male adults (>30 ng/mL). CONCLUSION: This present study demonstrated that serum PTH concentration showed negative correlation with eGFR, however, serum PTH increase may be minimized by maintaining proper serum 25(OH)D concentrations under similar eGFR status in Korean adults aged 50 and above.

The association between shift work and hyperuricemia in steelmaking male workers.

OBJECTIVES: The aim of this study was to examine the association between shift work and hyperuricemia among steel company workers. METHODS: We examined 1,029 male workers at a Korean steel company between June 6 and June 28, 2013. We conducted anthropometric measurements, questionnaire surveys, and blood tests. Hyperuricemia was defined as a serum uric acid concentration of ≥7.0 mg/dL. Logistic regression analyses were performed. In the full model, analysis was adjusted for covariates including age, body mass index, lifestyle factors, and comorbidities. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all models. RESULTS: The participants included 276 daytime workers and 753 shift workers. Among daytime workers, 72 (26.1%) individuals had hyperuricemia, as did 282 (37.5%) individuals among shift workers (p <0.001). There was a statistically significant association between shift work and hyperuricemia. In the unadjusted model, the OR of shift work was 1.70 (95% CI 1.25-2.31) for hyperuricemia. In the full model, the OR of shift work was also statistically significant after adjustment for covariates (OR 1.41, 95% CI 1.02-1.96). CONCLUSIONS: Among male steel workers, a significant association between shift work and hyperuricemia was observed.

The relevance of hyperuricemia and metabolic syndrome and the effect of blood lead level on uric Acid concentration in steelmaking workers.

OBJECTIVES: Uric acid concentration is known to increase the prevalence of metabolic syndrome by affecting its components, resulting in increased risk of cerebrovascular and cardiovascular diseases, and long-term lead exposure is known to affect this serum uric acid level. In this study, we aimed to examine the association between the causes of hyperuricemia and metabolic syndrome, and to determine whether an increased blood lead level affects hyperuricemia. METHOD: Anthropometric measurements, surveys, and blood tests were conducted between May and June 2012 in 759 men working in the steelmaking process at a domestic steel company. Workers were divided into 2 groups according to the presence or absence of hyperuricemia, and an analysis was performed to examine its association with metabolic syndrome. In addition, the workers were divided into 3 groups according to the blood lead level to analyze the association between blood lead and hyperuricemia. RESULTS: The geometric mean (standard deviation) of the blood lead levels in the hyperuricemia group was significantly higher than that of the healthy group (3.8 [1.8] vs. 3.3 [1.8] µg/dL). The adjusted odds ratio for metabolic syndrome of the hyperuricemia group increased significantly to 1.787 (1.125-2.839) compared with the healthy group. In addition, the adjusted odds ratios for the occurrence of hyperuricemia in the tertile 2 (2.61-4.50 µg/dL) and tertile 3 groups (>4.50 µg/dL) according to blood lead level significantly increased to 1.763 (1.116-2.784) and 1.982 (1.254-3.132), respectively, compared with the tertile 1 group (< 2.61 µg/dL). CONCLUSION: Hyperuricemia is believed to function as an independent risk factor for metabolic syndrome, while lead seems to increase the serum uric acid level even at a considerably low blood level. Therefore, attention should be given to patients with hyperuricemia and metabolic syndrome who are prone to lead exposure, and a prospective study should be conducted to identify their causal relationship.

Mechanical dyssynchrony assessed by tissue Doppler imaging is a powerful predictor of mortality in congestive heart failure with normal QRS duration.

OBJECTIVES: We sought to test whether the mechanical dyssynchrony assessed by tissue Doppler imaging (TDI) is a predictor of cardiac events in patients with congestive heart failure (CHF) and QRS duration < or =120 ms. BACKGROUND: The prevalence and prognostic value of mechanical dyssynchrony in patients with CHF and normal QRS duration have not been well clarified. METHODS: A total of 106 patients (age 63 +/- 11 years) with CHF and ejection fraction (EF) <35% were followed serially; TDI was performed using four basal and four mid-left ventricular segments to assess the time to peak systolic point from R-wave on electrocardiogram (Ts). The standard deviation of Ts (Ts-SD) and the maximal temporal difference of Ts (Ts-diff) of eight segments were used as an indicator of mechanical dyssynchrony. Clinical events included readmission due to worsening of CHF, cardiac transplantation, and death. RESULTS: After 17 +/- 11 months of follow-up, the clinical event rate was 33% including all-cause mortality of 19%. Prolonged Ts-SD (>37 ms) and Ts-diff (>91 ms) were associated with a significant increase in all clinical events. By multivariate analysis, Ts-diff (>91 ms) was an independent risk factor of clinical events and mortality regardless of age, EF, QRS duration, and use of beta-blocking agents. Mean event-free survival was 16.3 months (95% confidence interval [CI] 11.9 to 20.7) in patients with Ts-diff >91 ms and 31.6 months (95% CI 28.0 to 35.1) in those with Ts-diff < or =91 ms, respectively (p < 0.001). CONCLUSIONS: Myocardial dyssynchrony assessed by TDI is a powerful predictor of clinical events in CHF with normal QRS.

Effect of preexisting statin use on expression of C-reactive protein, adhesion molecules, interleukin-6, and antioxidized low-density lipoprotein antibody in patients with unstable angina undergoing coronary stenting.

BACKGROUND: Statins are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol lowering effect. HYPOTHESIS: We studied the effect of statins on expression of C-reactive protein (CRP), interleukin-6 (IL-6), adhesion molecules, and antioxidized low-density lipoprotein antibody (anti-oxLDL Ab) in patients with unstable angina (Braunwald class IIb or IIIb) undergoing coronary stenting. METHODS: Consecutive 50 patients with unstable angina were included in the study. We classified the study subjects as patients using statins (Group A, n=20, men 10, mean age 62 years) and patients not using statins (Group B, n=30, men 15, mean age 60 years). RESULTS: Baseline levels of inflammatory markers were similar in the two groups. However, 24 h after coronary stenting, serum levels of CRP (2.00 vs. 4.63 mg/l, p < 0.05), intercellular adhesion molecule-1 (ICAM-1) (217 vs. 261 ng/ml, p < 0.01), and anti-oxLDL Ab (8.97 vs. 12.96 U/ml, p < 0.05) were significantly higher in Group B than in Group A. Furthermore, 72 h after coronary stenting, serum levels of CRP (3.00 vs. 5.50 mg/l, p < 0.01) and ICAM-1 (222 vs. 277 ng/ml, p < 0.05) were significantly higher in Group B than in Group A. CONCLUSIONS: Preexisting statin therapy plays a role in reducing the serum levels of CRP, ICAM-1, and anti-oxLDL Ab after coronary stenting in patients with unstable angina. These data support an anti-inflammatory or plaque-stabilizing effect of statin therapy.