Background: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. Objectives: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. Methods: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. Results: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. Conclusions These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

A 42-year-old man presented with severe pancytopenia and uncontrolled epistaxis. The diagnosis of SLE was made and the pancytopenia was found to be due to myelofibrosis. The pulse therapy with methylprednisolone and maintenance therapy with prednisolone reversed both pancytopenia and myelofibrosis. Although myelofibrosis has been described in SLE, this coexistence must be very rare since there has been only 19 cases showing this combination. We report a case of SLE with myelofibrosis which was reversed by the treatment with glucocorticoid.
Adult ; Diagnosis ; Epistaxis ; Humans ; Lupus Erythematosus, Systemic* ; Methylprednisolone ; Pancytopenia ; Prednisolone ; Primary Myelofibrosis*

BACKGROUND: The neuropathy disability score (NDS) is a type of clinical grading method for diabetic polyneuropathy. In clinical practice, a nerve conduction study (NCS) is routinely employed as a non-invasive test for the evaluation of polyneuropathy. However, the consensus regarding the degree of abnormalities in NCS as a parameter for the severity of the disease is lacking. The objective of our study is to assess the relation between NDS and NCS parameters and thus verifying the reliability of our new NCS grading method in the representation of objective neurological defects. METHODS: Seventy three patients (man 31, women 42) with diabetes mellitus were included in the study. The NDS was scored in each patient by a single examiner and a NCS was performed on one side of extremities by an experiencedtechnician. Also, the gastrocnemius-soleus H-reflex was performed and analysed for the representation of a deep tendon reflex. The observed values of CMAP and CNAP were transformed into square root and log values. The transformed individual amplitudes and nerve conduction velocities were graded in relation to the mean normal values and standard deviations of our control group study. Then, the sum of the graded score was calculated in each individual and was correlated to the NDS using correlational analysis. RESULTS: There has been a significant linear relationship between NDS and our new NCS scoring system (Pearson's correlation coefficient r=0.703, p<0.01) CONCLUSIONS: The study showed significant correlations between NDS and our new grading system for NCS. Thus, NCS appears to reliably represent theobjective neurologic findings. In asddition, the quantititive grading of NCS would be useful in determining the grade of peripheral polyneuropathy in diabetic patients.
Consensus ; Diabetes Mellitus ; Diabetic Neuropathies* ; Extremities ; Female ; H-Reflex ; Humans ; Neural Conduction ; Neurologic Manifestations ; Polyneuropathies ; Reference Values ; Reflex, Stretch

Glutamate is a representative excitatory neurotransmitter. However, excessive glutamate exposure causes neuronal cell damage by generating neuronal excitotoxicity. Excitotoxicity in neonates caused by glutamate treatment induces neurological deficits in adults. The 14–3-3 family proteins are conserved proteins that are expressed ubiquitously in a variety of tissues. These proteins contribute to cellular processes, including signal transduction, protein synthesis, and cell cycle control. We proposed that glutamate induces neuronal cell damage by regulating 14–3-3 protein expression in newborn animals. In this study, we investigated the histopathological changes and 14–3-3 proteins expressions as a result of glutamate exposure in the neonatal cerebral cortex. Rat pups at post-natal day 7 were intraperitoneally administrated with vehicle or glutamate (10 mg/kg). Animals were sacrificed 4 h after treatment, and brain tissues were fixed for histological study. Cerebral cortices were isolated and frozen for proteomic study. We observed serious histopathological damages including shrunken dendrites and atypical neurons in glutamate-treated cerebral cortices. In addition, we identified that 14–3-3 family proteins decreased in glutamate-exposed cerebral cortices using a proteomic approach. Moreover, Western blot analysis provided results that glutamate treatment in neonates decreased 14–3-3 family proteins expressions, including the β/α, ζ/δ, γ, ε, τ, and η isoforms. 14–3-3 proteins are involved in signal transduction, metabolism, and anti-apoptotic functions. Thus, our findings suggest that glutamate induces neonatal neuronal cell damage by modulating 14–3-3 protein expression.

Background: Retinoic acid is a major metabolite of vitamin A and exerts beneficial effects including anti-oxidant and anti-inflammatory activities in neurons. The ubiquitin–proteasome system is an important biological system that regulates cell survival. Ubiquitination regulates protein degradation and plays an important role in oxidative stress. Deubiquitinating enzymes cleave ubiquitin from proteins and control ubiquitination-induced degradation. We detected decreases in ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic damage. In this study, we investigated whether retinoic acid regulates the expression of deubiquitinating enzymes ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic injury. Right middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemic damage in male rats. Retinoic acid (5 mg/kg) or vehicle was intraperitoneally injected every day from 4 days before surgery. Neurological behavioral tests were performed 24 h after MCAO, and right cerebral cortical tissues were collected. Results: MCAO damage caused neurological behavioral dysfunction, and retinoic acid alleviated these deficits. The identified proteins decreased in MCAO animals with vehicle, while retinoic acid treatment attenuated these decreases.The results of proteomic study were confirmed by a reverse transcription-PCR technique. Expressions of ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 were decreased in MCAO animals treated with vehicle. Retinoic acid treatment alleviated these MCAO-induced reductions. The ubiquitin–proteasome system plays an essential role in maintaining cell function and preserving cell shape against ischemic damage. Conclusions These findings suggest that retinoic acid regulates ubiquitin- and proteasome-related proteins including ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in a brain ischemia model. Changes in these proteins are involved in the neuroprotective effects of retinoic acid.

Background: and Purpose Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy– Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. Methods: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). Results: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. Conclusions These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

Broncholithiasis is uncommon in patients with silicosis. Bronchoesophageal fistula complicated by broncholithiasis is especially rare and only one case has been reported in Korea. Surgical treatment of broncholithiasis should be as conservative as possible to preserve the adequate pulmonary function. Meticulous dissection and division of the fistula with the interposition of viable tissues will prevent recurrence. We report a rare case of bronchoesophageal fistula complicated by broncholithiasis in a patient with silicosis.

Background: In the face of the unexpected coronavirus disease 2019 (COVID-19) pandemic, every country has struggled with insufficient human resources and medical supplies. This study aims to provide the statistical information necessary for discussing how to model stockpiles of medical resources. Methods: This study was conducted at the Hallym University Kangnam Sacred Heart Hospital, in South Korea. The study duration was 2 weeks, centered on March 16, 2022, when the number of daily confirmed patients with COVID-19 in Korea peaked. The number of human resources was obtained by counting the number of healthcare workers using CCTV. Drug prescriptions and medical device usage were obtained from electronic medical records. Results: In total, 117 inpatients and 26,485 outpatients were managed at this hospital during the 2-week study period. Daily visits were highest among nurses in all units, followed by doctors and radiology technicians. The mean daily consumption of personal protective equipment (PPE) per bed was 4.3 sets in the intensive care unit (ICU), 1.8 in the semi-ICU, and 1.4 in the ward. Despite the four-fold difference in the number of patients, there was no statistically significant difference between the two wards in the number of daily visits. Drug prescription rates were higher among inpatients than at-home patients. Conclusions The higher the COVID-19 severity, the higher the consumption of PPE per patient. Among healthcare workers, nurses had the highest number of inpatient treatment visits for COVID-19. To efficiently utilize, PPE, structures containing more isolation beds in a single negative pressure isolation system would be preferred.

BACKGROUND AND OBJECTIVES: Both carotid intima-media thickness (CIMT) and carotid plaque are important factors in the primary prevention of cardiac disease. However, it is unclear which one is more important for prognosis, especially in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: In total, 1426 consecutive CAD patients, proven by angiography, were followed-up for a mean of 85 months. The study population was divided into four groups depending on the CIMT (> or =0.83 mm, >95 percentile in Korea) and the presence or absence of carotid plaque. RESULTS: Patients with carotid plaque and thick CIMT (n=237, 16.6%) had a higher prevalence of hypertension, diabetes mellitus, and dyslipidemia than those had plaque and thin CIMT (n=213, 14.9%), those without plaque and thick CIMT (n=265, 18.6%) and those without plaque and thin CIMT (n=711, 49.9%). The patients with carotid plaque and thick CIMT group had a higher cardiac mortality rate (20.7% vs. 13.1%, 9.4% and 3.9%, respectively, p<0.001) and higher major adverse cardiovascular events (MACE) including death, acute myocardial infarction, and stroke (27.8% vs. 18.8%, 15.5% and 9.3%, respectively, p<0.001) than any other groups. Multivariate Cox regression analysis showed that the presence of carotid plaque with thick CIMT had the highest hazard ratio (HR) compared to other groups (HR 2.23 vs. 1.81, 2.01) for cardiac mortality. Also, carotid plaque had a higher HR than CIMT for mortality (HR 1.56 vs. 1.37) and MACE (HR 1.54 vs. 1.36) in the total study population. CONCLUSION: Carotid plaque is a more important prognostic factor than CIMT in patients with CAD, and adding a thick CIMT to carotid plaque increases the prognostic power for cardiac events.
Angiography ; Carotid Intima-Media Thickness ; Carotid Stenosis ; Coronary Artery Disease* ; Diabetes Mellitus ; Dyslipidemias ; Follow-Up Studies* ; Heart Diseases ; Humans ; Hypertension ; Mortality ; Myocardial Infarction ; Prevalence ; Primary Prevention ; Prognosis ; Stroke ; Ultrasonography*

Recent genomewide association studies of large samples have identified genes that are associated with blood pressure. The Global Blood Pressure Genetics (Global BPgen) and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortiums identified 14 loci that govern blood pressure on a genomewide significance level, one of which is CASZ1 confirmed in both Europeans and Asians. CASZ1 is a zinc finger transcription factor that controls apoptosis and cell fate and suppresses neuroblastoma tumor growth by reprogramming gene expression, like a tumor suppressor. To validate the function of CASZ1 in blood pressure, we decreased Casz1 mRNA levels in mice by siRNA. Casz1 siRNA reduced mRNA levels by 59% in a mouse cell line. A polyethylenimine-mixed siRNA complex was injected into mouse tail veins, reducing Casz1 mRNA expression to 45% in the kidney. However, blood pressure in the treated mice was unaffected, despite a 55% reduction in Casz1 mRNA levels in the kidney on multiple siRNA injections daily. Even though Casz1 siRNA-treated mice did not experience any significant change in blood pressure, our study demonstrates the value of in vivo siRNA injection in analyzing the function of candidate genes identified by genomewide association studies.
Aging ; Animals ; Apoptosis ; Asian Continental Ancestry Group ; Blood Pressure ; Cell Line ; Cohort Studies ; Gene Expression ; Genome ; Heart ; Humans ; Kidney ; Mice ; Neuroblastoma ; RNA, Messenger ; RNA, Small Interfering ; Transcription Factors ; Veins ; Zinc Fingers