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Cyclophilin A (CypA), a cytosolic binding protein of cyclosporine A, is an immunosuppressive drug. In this study, CypA cDNA was cloned from the two-spotted cricket Gryllus bimaculatus (gCypA). The protein encoded by gCypA comprises 165 amino acids with a molecular mass of 19.23 kDa and an isoelectric point of 9.38 and possesses three N-glycosylation sites and 17 phosphorylation sites. The secondary and tertiary structures of gCypA were identified, and homology analysis revealed that it shares around 73%-81% sequence identities with other CypA proteins. When the researchers analyzed the expression levels of gCypA mRNA in various tissues, they found that the foregut exhibited nearly the same expression level as that of the dorsal longitudinal flight muscle (the control). However, gCypA mRNA expression in the fat body, Malpighian tubes, and midgut was less than half of that in the dorsal longitudinal flight muscle. Under endoplasmic reticulum stress conditions, gCypA mRNA expression was highest in Malpighian tubules (about two times higher than the expression in the control). Under starvation conditions, gCypA mRNA expression increased to three times that of the dorsal longitudinal flight muscle 6 days after starvation. Nonetheless, its expression levels decreased in Malpighian tubules under all starvation conditions. This study provides insights into the physiological role of gCypA in G. bimaculatus.

Thyroglobulin (Tg) is essential for thyroid hormone synthesis and thyroid function. Its levels are regulated by external environmental changes. Zinc is widely involved in cellular processes as a cofactor of enzymes and participates in metabolic processes. Here we investigated whether zinc depletion affected Tg production and secretion through the endoplasmic reticulum (ER) in the PCCL3 thyroid cell line exposed to the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (Tpen). Although zinc depletion did not affect the gene expression of ER chaperones (BiP and PDI), it increased the expression of ER transmembrane signaling proteins (PKR-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6)). This resulted in the activation of downstream factors as shown by the increase of eIF2-α phosphorylation, X-box binding protein 1 mRNA splicing, and ATF6 fragmentation. Zinc depletion induced an inhibition of Tg expression and secretion and activated apoptosis in PCCL3 cells. Moreover, a reduction of secreted T4 levels and histologically abnormal thyroid follicle structures were found after zinc depletion. Therefore, zinc depletion likely inhibited the biosynthesis and extracellular secretion of Tg through ER stress signaling. These findings provide valuable insight into zinc potential as a treatment of hyperthyroidism.

Although glibenclamide is an oral hypoglycemic agent used in type 2 diabetes, skeletal muscle wasting has been reported as a side effect. To understand how to reduce this side effect, we determined whether glibenclamide induces endoplasmic reticulum (ER) stress in skeletal muscle cells and which myokine expression changes at this time. The ER chaperone genes do not show a significant change by glibenclamide, but the ER stress sensor genes are upexpressed approximately twice, and those downstream [ATF6 (activating transcription factor 6) fragmentation, eIF2α (eukaryotic initiation factor-2α) phosphorylation, and XBP1 (Xbox DNA-binding protein) mRNA splicing] are activated. Additionally, the myokine gene expression was up- or downregulated by glibenclamide. These results will serve as useful data for overcoming the side effects of sarcopenia caused by glibenclamide.

Ultrasonography is an effective diagnostic tool for testicular torsion (TT), which is typically characterized by the absence of blood flow in the affected testicle on color Doppler mode. However, there are a few reported cases of TT with symmetrical preserved flow. We report a case of TT with the preserved intratesticular flow on color Doppler ultrasound.A 14-year-old boy was admitted due to sudden-onset right scrotal pain. Point-of-care ultrasound (POCUS) revealed that the right testicle was larger than the left. The intratesticular flow in both testicles was preserved. Radiology-performed ultrasound confirmed the preserved intratesticular flow observed on POCUS, but also demonstrated a whirlpool sign of the right spermatic cord. TT was confirmed surgically. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should investigate the presence of intratesticular blood flow and the whirlpool sign of the spermatic cord or other ultrasound features suggestive of TT, even if testicular blood flow is preserved. Suspicion of TT from POCUS findings warrants further evaluation to preserve the patient's fertility.

Background Aconitine is well-known for its potential analgesic, anti-inflammatory, and circulation promoting effects and has been widely used as a folk medicine in South Korea. Owing to its extremely toxic nature and relatively low safety margin, intoxication is sometimes fatal. The toxic compound mainly affects the central nervous system, heart, and muscle, resulting in cardiovascular complications. Purpose To determine the exact relationship between blood concentration of aconitine and clinical manifestation. Basic procedures The National Forensic Service (NFS) was commissioned to assist in a quantitative analysis of highly toxic aconitine and corresponding blood concentrations by analyzing the body fluids of three patients who were suspected of aconitine poisoning. Main findings Aconitine blood values tested by the NFS showed that patients with a blood concentration below a certain level developed symptoms slowly and showed a high severity of clinical manifestation. There was no correlation between blood concentration and symptoms or ECG results. Conclusions In case of suspected aconitine poisoning, an emergency care department should be visited, even with symptomatic improvement, and the patient should be monitored for at least 24 h, depending on the level of recovery and changes in ECG results.

Aim We presented the cut-off value of a diffusion-weighted image (DWI) scoring system to predict poor neurologic outcome using DWI taken 72−96 h after out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). Methods This was a prospective single-centre observational study, conducted from March 2018 to April 2020 in OHCA patients after TTM. Neurological status was assessed 6 months after return of spontaneous circulation (ROSC) using the Glasgow-Pittsburgh cerebral performance categories (CPC) scale. CPC of 1–2 demonstrated good neurologic outcomes whilst a CPC of 3–5 was related to poor neurologic outcomes. The receiver operating characteristic curves and DeLong method were used to evaluate the cut-off value of the DWI scoring system to predict poor neurologic outcome. Results The good and poor neurologic outcome groups consisted of 38 (54.3%) and 32 (45.7%) patients, respectively. The area under the receiver operating characteristic curve (AUROC) of the overall, cortex, deep grey nuclei, and cortex plus deep grey nuclei scores, white matter, brainstem, and cerebellum measured 72−96 h after ROSC were 0.96, 0.96, 0.97, 0.96, 0.95, 0.95, and 0.93 respectively. For 100.0% specificity to predict poor neurologic outcome, the overall scores of the DWI scoring system measured 72−96 h after ROSC with a cut-off value of 52 had a sensitivity of 81.3% (95% CI: 63.6–92.8). Conclusion This study demonstrated that the DWI scoring systems measured between 72 and 96 h after ROSC were valuable tools to predict poor neurologic outcome in post-OHCA patients treated with TTM.

Aim In a previous study, low and high-normal arterial carbon dioxide tension (PaCO2) were not associated with serum neuron-specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO2 on NSE in cerebrospinal fluid (CSF) and serum. Methods This was a retrospective study. PaCO2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum–maximum (Min–Max). These subgroups were divided into low (LCO2) and high PaCO2 (HCO2) groups defined as PaCO2 ≤ 35.3 and PaCO2 > 43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE24,48,72 and cNSE24,48,72) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO2 and the NSE measured at 24 h after ROSC. Results Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO2 in TWA subgroup was associated with cNSE24,48,72, while PaCO2 in the other subgroup were only associated with cNSE24. PaCO2 and cNSE in qES subgroup showed good correlation (r = −0.61; p Conclusion Association was found between NSE and PaCO2 using CSF, despite including normocapnic ranges; TWA of PaCO2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.

Aim This study examined whether the presence of cortical necrosis (CN) on ultra-early diffusion-weighted imaging (DWI) and the severity of cytotoxic oedema (CytE) with cerebral oedema (CbrE), measured using quantitative analysis of apparent diffusion coefficient (ADC), could predict neurological outcomes before targeted temperature management in out-of-hospital cardiac arrest survivors (OHCAs). Methods In this retrospective study, the first DWI with ADC scans was performed within 6 h; the second was obtained between 72 and 96 h after return of spontaneous circulation. The primary outcome was neurological outcomes at 6 months after OHCA. The % voxels of ADC value (PV) was calculated; CbrE and CytE values were > or Results Thirty-six patients were included. CN (area under receiver operating characteristic curve [AUC] = 0.800), thld-CytE (PV420; AUC = 0.730), and thld-CbrE (PV1090; AUC = 0.775) showed meaningful performance, and the combined score showed best performance for poor outcome prediction (AUC = 0.956). DWI findings of CN patients was worse at the second DWI. ΔPV significantly increased in the poor outcome group, CN patients, and the group including both, thld-CytE and thld-CbrE. Conclusions In OHCAs, ultra-early DWI with ADC could successfully predict poor neurological outcomes by combining scores of CN, thld-CytE, and thld-CbrE.

We compared the cut-off and prognostic value of serum neuron-specific enolase (NSE) between groups with and without severe blood–brain barrier (BBB) disruption to reveal that a cause of various serum NSE cut-off value for neurological prognosis is severe BBB disruption in out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). This was a prospective, single-centre study conducted from January 2019 to June 2021. Severe BBB disruption was indicated using cerebrospinal fluid-serum albumin quotient values > 0.02. The area under the receiver operating characteristic curve of serum NSE obtained on day 3 of hospitalisation to predict poor outcomes was used. In patients with poor neurologic outcomes, serum NSE in those with severe BBB disruption was higher than in those without (P = 0.006). A serum NSE cut-off value of 40.4 μg/L for poor outcomes in patients without severe BBB disruption had a sensitivity of 41.7% and a specificity of 96.0%, whereas a cut-off value of 34.6 μg/L in those with severe BBB disruption had a sensitivity of 86.4% and a specificity of 100.0%. We demonstrated that the cut-off and prognostic value of serum NSE were heterogeneous, depending on severe BBB disruption in OHCA patients treated with TTM.

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf-stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site-selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p-MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague-Dawley rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p-MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p-MN for the heparin-pretreated SD rat model is demonstrated by intravenous injection in vivo. This article is protected by copyright. All rights reserved.

The diarylheptanoid, 5-hydroxy-7-(4”-hydroxy-3”-metho-xyphenyl)-1-phenyl-3-heptanone (HPH), is isolated from rhizomes of Alpinia officinarum. There is no reported biological function for this compound other than the inhibition of pancreatic lipase. Cell viability, the expression of endoplasmic reticulum (ER) stress genes, the activation of ER stress sensors, and the induction of apoptosis and autophagy were confirmed following HPH treatment of PC12 cells. No cytotoxicity was observed when the cells were treated with 50 μg/ml HPH, but 40% cell death was observed using MTT assays with 100 μg/ml HPH. Although HPH did not change the expression of the ER chaperones PDI, binding BiP, and calnexin, it upregulated the expression of genes for the ER stress sensors ATF6, eIF2α, and PERK. HPH also induced apoptosis via the activation of ATF6 fragmentation, the phosphorylation of eIF2α, and XBP1 mRNA splicing. Eventually, the results of this study demonstrated that HPH induces apoptosis through upregulation of gene expression of ER stress sensors, which may provide a basis for the development of new drugs using HPH.

Studies on the prognostic performance of optic nerve sheath diameter (ONSD) in out-of-hospital cardiac arrest survivors (OHCA) have reported conflicting results. We aimed to investigate the usefulness of ONSD measured using magnetic resonance imaging (MRI) to estimate its association with intracranial pressure (ICP) and 6-month neurological outcomes in CA survivors treated with targeted temperature management (TTM).This retrospective study included 37 CA survivors who underwent TTM from January 2018 to December 2018. ICP was measured by lumbar catheter during TTM on Days 0, 1, 2, and 3. ONSD was measured using MRI on Days 0 and 3. The primary outcome was the correlation between ONSD and ICP associated with neurological outcomes obtained after 6 months.The median (interquartile range [IQR]) ONSD was not significantly different between the good and poor neurological outcome group on Day 0 (5.2 mm [4.8-5.8] vs 5.2 mm [4.8-5.6]; p = 0.948) and Day 3 (5.0 mm [4.8-5.2] vs 5.5 mm [4.4-5.9]; p = 0.105). ONSD and ICP had excellent correlation on Day 3 (r = 0.90, p 0.001). ONSD showed excellent correlation with increased ICP (IICP) defined as ICP above 20 mmHg (r = 0.89, p 0.001). ONSD cut-off of 5.99 mm was used with a sensitivity of 90.0% and specificity of 98.0% to identify IICP.The ONSD on Days 0 or 3 did not show differences in neurological outcomes in OHCA patients treated with TTM. However, ONSD had an excellent correlation with ICP on Day 3 and with IICP. Further studies are required to confirm our results.

Aim We evaluated the optimal timing of optic nerve sheath diameter (ONSD) measurement to predict neurologic outcome in post-cardiac arrest patients treated with target temperature management (TTM). Methods This was a prospective single-centre observational study from April 2018 to March 2019. Good outcome was defined as the Glasgow-Pittsburgh cerebral performance categories (CPC) 1 or 2, and poor outcome as a CPC between 3 and 5. ONSD was measured initially after return of spontaneous circulation (ROSC) (ONSDinitial), at 24 h (ONSD24), 48 h (ONSD48), and 72 h (ONSD72) using ultrasonography. The receiver operating characteristic (ROC) curves and DeLong method were used to compare the values for predicting neurologic outcomes. Results Out of the 36 patients enrolled, 18 had a good outcome. ONSD24, ONSD48, and ONSD72 were higher in the poor outcome group. The area under ROC curve of ONSD24 was 0.91 (95% confidence interval 0.77–0.98) in predicting poor neurologic outcomes. With a cut off value of 4.90 mm, ONSD24 had a sensitivity of 83.3% and a specificity of 94.4% in predicting poor neurologic outcomes. Conclusion Our findings demonstrate ONSD24 as a valuable tool to predict the neurologic outcome in post-cardiac arrest patients treated with TTM. Therefore, we recommend performing ONSD measurement using ultrasonography at 24 h after ROSC, rather than immediately after ROSC, to predict neurologic outcome in post-cardiac arrest patients treated with TTM.

Purpose Brain swelling post-cardiac arrest may affect cerebrospinal fluid volume. We aimed to investigate the prognostic performance of the proportion of cerebrospinal fluid volume (pCSFV) using brain computed tomography (CT) in cardiac arrest survivors. Materials and Methods This retrospective multicentre study included adult comatose cardiac arrest survivors who underwent brain CT scan prior to target temperature management (TTM) from 2015 to 2016. Grey-to-white matter ratio (GWR) and pCSFV values were calculated. pCSFV analysis was performed using automated quantitative analysis programming. The primary outcome was a 6-month neurological outcome. Results Of 251 patients (median age, 57 years), 173 (68.9%) were male, 87 (34.7%) had a shockable rhythm, and 160 (63.7%) had unfavourable neurological outcomes. GWR but not pCSFV was significantly higher in terms of favourable neurological outcomes (p = .015). pCSFV prognostic performances were similar to GWR, and were poor overall, (0.521; 95% confidence interval [CI], 0.446–0.694 vs. 0.515; 95% CI, 0.441–0.589). After adjusting for covariates, pCSFV but not GWR was independently associated with neurological outcome 6 months following cardiac arrest (p = .049). Conclusion pCSFV was independently associated with neurological outcome 6 months following cardiac arrest, however prognostic performance was not good.

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general

Background The use of personal protective equipment for respiratory infection control during cardiopulmonary resuscitation (CPR) is a physical burden to healthcare providers. The duration for which CPR quality according to recommended guidelines can be maintained under these circumstances is important. We investigated whether a 2-min shift was appropriate for chest compression and determined the duration for which chest compression was maintained in accordance with the recommended guidelines while wearing personal protective equipment. Methods This prospective crossover simulation study was performed at a single center from September 2020 to October 2020. Five indicators of CPR quality were measured during the first and second sessions of the study period. All participants wore a Level D powered air-purifying respirator (PAPR), and the experiment was conducted using a Resusci Anne manikin, which can measure the quality of chest compressions. Each participant conducted two sessions. In Session 1, the sequence of 2 min of chest compressions, followed by a 2-min rest, was repeated twice; in Session 2, the sequence of 1-min chest compressions followed by a 1-min rest was repeated four times. Results All 34 participants completed the study. The sufficiently deep compression rate was 65.9 ± 31.1% in the 1-min shift group and 61.5 ± 30.5% in the 2-min shift group. The mean compression depth was 52.8 ± 4.3 mm in the 1-min shift group and 51.0 ± 6.1 mm in the 2-min shift group. These two parameters were significantly different between the two groups. There was no significant difference in the other values related to CPR quality. Conclusions Our findings indicated that 1 min of chest compressions with a 1-min rest maintained a better quality of CPR while wearing a PAPR.

Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade.This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (0.007).Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 μg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P.01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort.Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.

This retrospective cohort study aimed to compare the effectiveness of conventional treatment and ultra-early application of negative pressure wound therapy (NPWT) in patients with snakebites. Patients who visited the emergency department within 24 hours after a snakebite were assigned to the non- NPWT or NPWT group. Swelling resolution time and rates of necrosis, infection, and operations were compared between the 2 groups. The Stony Brook Scar Evaluation Scale was used to measure short- and long-term wound healing results. Among the included 61 patients, the swelling resolution time was significantly shorter in the NPWT group than in non- NPWT group (P = .010). The NPWT group showed lower necrosis (4.3% versus 36.8%; P = .003) and infection (13.2% and 4.3%; P = .258) rates than the non- NPWT group. The median Stony Brook Scar Evaluation Scale scores were higher in the NPWT group than in the non- NPWT group (P

Pectolinarin, [5,7-Dihydroxy 4',6-dimethoxyflavone 7-rutinoside, 7-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl] oxy]-5-hydroxy-6-methoxy-2-(4-ethoxyphenyl)-4H-1-benzopyran-4-one], has been stated one of the major compounds in Cirsium nipponicum (Maxim.) Makino. It is characterized by biological functions of hepatoprotective, anti-inflammatory and antiobesity activities. In this research, it was explained that pectolinarin causes apoptosis in PC12 cells conducted by DNA fragmentation and formation on apoptotic bodies through the activation of ER stress sensors (ATF6 fragmentation and eIF2α phosphorylation). The result of treating the PC12 cells with 50 μM pectolinarin for 24 h has come to increase ATF6 mRNA expression up to 1.6 times, PERK expression up to 1.7 times and IRE1 expression up to 1.4 times, respectively, compared to those of the control. ATF6 fragmentation by pectolinarin treatment was increased about 2 times compared with its control, and phosphorylation of eIF2α was increased 2.5 times. The results proposed that the perception of the molecular mechanisms underlying pectolinarin-caused apoptosis may be useful in new natural medicinal products and health supplements for the apoptosis-related diseases.

Aim We aimed to evaluate the onset of severe blood-brain barrier (BBB) disruption using cerebrospinal fluid/serum albumin quotient (Qa) in cardiac arrest patients treated with target temperature management (TTM). Methods This was a prospective single-centre observational cohort study from October 2017 to September 2018 with the primary endpoint being the onset of severe BBB disruption, determined based on Qa in cardiac arrest patients treated with TTM. Enrolled patients were grouped according to neurologically good and poor outcomes using the cerebral performance category (CPC) at 3 months after return of spontaneous circulation (ROSC). Severe BBB disruption was evaluated using Qa measured immediately (Qa0) and at 24 h (Qa24), 48 h (Qa48), 72 h (Qa72) after ROSC. Results Of 21 patients enrolled, poor outcome group had 10 patients. Qa0 was 0.019 (0.008∼0.024) in the poor outcome group and 0.006 (0.003∼0.008) in the good outcome group (p = 0.09). Qa24 was 0.045 (0.025∼0.115) in the poor outcome group and 0.006 (0.003∼0.006) in the good outcome group (p = 0.03). Qa48 was 0.055 (0.023∼0.276) in the poor outcome group and 0.006 (0.006∼0.009) in the good outcome group (p = 0.02). Qa72 was 0.047 (0.026∼0.431) in the poor outcome group and 0.007 (0.005∼0.011) in the good outcome group (p = 0.02). Conclusion Qa was significantly higher in the poor outcome group at 24 h, 48 h, and 72 h. Severe BBB disruption indicated by Qa ≥ 0.02 in poor outcome group treated with TTM occurred within the first 24 h after ROSC.

Clusterin (CLU) is a heterodimeric glycoprotein involved in a range of biological processes. We investigated the function of CLU as a novel regulator of adipogenesis. CLU expression increased during 3T3-L1 preadipocyte differentiation. CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). Conversely, knockdown of CLU attenuated adipogenesis and reduced transcript levels of Pparg and Cebpa. However, the promoter activities of both the Pparg and the Cebpa gene were not affected by alteration of CLU expression on its own. Additionally, the protein level of Kruppel-like factor 5 (KLF5), an upstream transcription factor of Pparg and Cebpa involved in adipogenic differentiation, was upregulated by CLU overexpression, although the mRNA level of Klf5 was not altered by changes in the expression level of CLU. Cycloheximide chase assay showed that the increased level of KLF5 by CLU overexpression was due to decreased degradation of KLF5 protein. Interestingly, CLU increased the stability of KLF5 by decreasing KLF5 ubiquitination. CLU inhibited the interaction between KLF5 and F-box/WD repeat-containing protein 7, which is an E3 ubiquitin ligase that targets KLF5. The adipogenic role of CLU was also addressed in mesenchymal stem cells (MSCs) and Clu-/- mouse embryonic fibroblasts (MEFs). Furthermore, CLU enhanced KLF5-mediated transcriptional activation of both the Cebpa and the Pparg promoter. Taken together, these results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5.

Incidences of brain death due to nicotine overdose by e-cigarettes have been increasing. In such cases, liver donation has been not reported because of the secondary damage to the liver due to metabolism of large amounts of nicotine. However, kidneys have been considered acceptable for transplant. Here, we present a successful case of liver transplant from a brain-dead donor due to intentional nicotine ingestion who did not have extensive steatosis. To the best of our knowledge, this is the first report of such a case.

Aim The optimal time to measure serum albumin concentration (SAC) to predict prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the relationships between time-related SAC, optic nerve sheath diameter (ONSD), intracranial pressure (ICP), and neurological prognosis in CA survivors. Methods We undertook a retrospective study examining CA patients treated with target temperature management (TTM). ICP was measured using cerebrospinal fluid (CSF) pressure and ONSD was obtained before TTM. SAC was measured repeatedly at 4–6 h intervals from the hospital arrival time. We analysed CSF pressure, ONSD, and minimum SAC (MSAC) separately, or in combination, to predict poor neurological outcome. Results Of 83 patients enrolled, the good outcome group comprised 25 (34%) patients. MSAC at 24 h (MSAC24) had a higher area under the receiver operating characteristic curve (AUC) (0.687; 95% confidence interval (CI), 0.668–0.926) than other time points. CSF pressure showed a higher AUC (0.973; 95% CI, 0.911–0.996) than MSAC24 and ONSD (0.677; 95% CI, 0.565–0.776). In contrast to using MSAC24 and ONSD separately, the combination of both modalities resulted in a better AUC, thus improving the prediction of the neurological outcome (0.734; 95% CI, 0.626–0.825) and ICP (0.758; 95% CI, 0.651–0.845) after return of spontaneous circulation (ROSC) from CA. Conclusion A higher ICP was strongly associated with and seemed predictive of poor outcome. Furthermore, the MSAC24/ONSD combination may be a useful predictor of high ICP and poor neurological outcome. Prospective studies should be conducted to confirm these results.

OBJECTIVE Patients are often transported within the hospital, especially in cases of critical illness for which computed tomography (CT) is performed. Since increased transport time increases the risks of complications, reducing transport time is important for patient safety. This study aimed to evaluate the ability of our newly invented device, the Easy Tube Arrange Device (ETAD), to reduce transport time for CT evaluation in cases of critical illness. METHODS This prospective randomized control study included 60 volunteers. Each participant arranged five or six intravenous fluid lines, monitoring lines (noninvasive blood pressure, electrocardiography, central venous pressure, arterial catheter), and therapeutic equipment (O2 supply device, Foley catheter) on a Resusci Anne mannequin. We measured transport time for the CT evaluation by using conventional and ETAD method. RESULTS The median transport time for CT evaluation was 488.50 seconds (95% confidence interval [CI], 462.75 to 514.75) and, 503.50 seconds (95% CI, 489.50 to 526.75) with 5 and 6 fluid lines using the conventional method and 364.50 seconds (95% CI, 335.00 to 388.75), and 363.50 seconds (95% CI, 331.75 to 377.75) with ETAD (all P

In this study, we evaluated the effects of various hypothermic conditions (32℃), including lithium chloride treatment, on insulin-like growth factor 1 (IGF-1) gene expression in PC12 cells. The results show that short-term hypothermic treatment ( 1 day). Repeated switching between normal temperature and hypothermia every 2 h increased IGF-1 gene expression approximately 3-4-fold. These findings indicate that hypothermia dynamically regulates IGF-1 gene expression. This study could be helpful for the development of treatment and diagnostic strategies for ischemia.

Insulin secretion from pancreatic islet β-cells is primarily regulated by the blood glucose level, and also modulated by a number of biological factors produced inside the islets or released from remote organs. Previous studies have shown that angiopoietin-like protein 4 (Angptl4) controls glucose and lipid metabolism through its actions in the liver, adipose tissue, and skeletal muscles. In this present study, we investigated the possible role of Angptl4 in the regulation of insulin secretion from pancreatic islets. Angptl4 was found to be highly expressed in the α-cells but not β-cells of rodent islets. Moreover, treatment of rodent islets with Angptl4 peptide potentiated glucose-stimulated insulin secretion through a protein kinase A-dependent mechanism. Consistently, Angptl4 knockout mice showed impaired glucose tolerance. In the cultured islets from Angptl4 knockout mice, glucose-stimulated insulin secretion was significantly lower than in islets from wild type mice. Angptl4 peptide replacement partially reversed this reduction. Moreover, Angptl4 knockout mice had dysmorphic islets with abnormally distributed α-cells. In contrast, the β-cell mass and distribution were not significantly altered in these knockout mice. Our current data collectively suggest that Angptl4 may play a critical role in the regulation of insulin secretion and islet morphogenesis.

Aim We evaluated the prognostic value of serum- and cerebrospinal fluid (CSF)-ubiquitin carboxyl-terminal esterase L1 protein (UCHL1) measurements in post- post-out of hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM), to predict neurologic outcome. Methods This was a prospective single-centre observational cohort study, conducted from April 2018 to September 2019. Serum- and CSF-UCHL1 were obtained immediately (UCHL1initial), 24 h (UCHL124), 48 h (UCHL148), and 72 h (UCHL172) after return of spontaneous circulation (ROSC). The area under the receiver operating characteristic curves (AUROC) and Delong method were used to identify cut-off values of serum- and CSF-UCHL1initial, UCHL124, UCHL148, UCHL172 for predicting neurologic outcomes. Results Of 38 patients enrolled, 16 comprised the poor outcome group. The AUROCs for serum- and CSF-UCHL1initial were 0.71 and 0.93 in predicting poor neurological outcomes, respectively (p = 0.01). The AUROCs for serum- and CSF-UCHL124 were 0.85 and 0.91 (p = 0.24). The AUROCs for serum- and CSF-UCHL148 were 0.90 and 0.97 (p = 0.07). The AUROCs for serum- and CSF-UCHL172 were 0.94 and 0.98 (p = 0.25). Conclusion Findings of this study demonstrate that CSF-UCHL1 measured immediately, 24, 48, and 72 h after ROSC is a valuable predictor for evaluating neurologic outcomes, whereas serum-UCHL1 measured at 24, 48, and 72 h after ROSC showed a significant performance in the prognostication of poor outcomes in post-OHCA patients treated with TTM.

Purpose Cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) levels increase in patients with brain injury. We investigated neurologic outcomes associated with CSF LDH levels in out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). Materials and methods This was a prospective single-centre observational study from April 2018 to May 2019 on a cohort of 41 patients. CSF and serum LDH samples were obtained immediately (LDH0) and at 24 (LDH24), 48 (LDH48), and 72 h (LDH72) after return of spontaneous circulation (ROSC). Neurologic outcomes were assessed at 3 months after ROSC using the Cerebral Performance Category scale. Results Twenty-one patients had a poor neurologic outcome. CSF LDH levels were significantly higher in the poor neurologic outcome group at each time point. The area under the curve (AUC) of CSF LDH48 was 0.941 (95% confidence interval [CI], 0.806–0.992). With a cut off value of 250 U/L, CSF LDH48 had a high sensitivity (94.1%; 95% CI, 71.3–99.9) at 100% specificity. Conclusions CSF LDH level at 48 h was a highly specific and sensitive marker for 3-month poor neurologic outcome. This may constitute a useful predictive marker for neurologic outcome in OHCA survivors treated with TTM.

Aim Cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels increase ahead of serum NSE levels in patients with severe brain injury. We examined the prognostic performance between CSF NSE and serum NSE levels in out-of-cardiac arrest (OHCA) survivors who had undergone target temperature management (TTM). Methods This single-centre prospective observational study included OHCA patients who had undergone TTM. NSE levels were assessed in blood and CSF samples obtained immediately (Day 0), and at 24 h (Day 1), 48 h (Day 2), and 72 h (Day 3) after return of spontaneous circulation (ROSC). The primary outcome was the 6-month neurological outcome. Results We enrolled 34 patients (males, 24; 70.6%), and 16 (47.1%) had a poor neurologic outcome. CSF NSE and serum NSE values were significantly higher in the poor outcome group compared to the good outcome group at each time point, except for serum Day 0. CSF NSE and serum NSE had an area under curve (AUC) of 0.819–0.972 and 0.648–0.920, respectively. CSF NSE prognostic performances were significantly higher than serum NSE levels at Day 1 and showed excellent AUC values (0.969; 95% confidence interval [CI] 0.844–0.999) and high sensitivity (93.8%; 95% CI 69.8–99.8) at 100% specificity. Conclusion We found CSF NSE values were highly predictive and sensitive markers of 6-month poor neurological outcome in OHCA survivors treated with TTM at Day 1 after ROSC. Therefore, CSF NSE levels at day 1 after ROSC can be a useful early prognosticator in OHCA survivors.

This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. We retrospectively analyzed non-traumatic OHCA survivors treated with TTM. The primary outcome was poor neurological outcome at 3 months after return of spontaneous circulation (cerebral performance category, 3–5). We compared neurological prognostic performance using existing models after adding objective data obtained before TTM from computed tomography (CT), magnetic resonance imaging (MRI), and biomarkers to replace the no-flow time component of the OHCA and CAHP models. Among 106 patients, 61 (57.5%) had poor neurologic outcomes. The area under the receiver operating characteristic (AUROC) curve for the OHCA and CAHP models was 0.89 (95% confidence interval (CI) 0.81–0.94) and 0.90 (95% CI 0.82–0.95), respectively. The prediction of poor neurological outcome improved after replacing no-flow time with a grey/white matter ratio measured using CT, high-signal intensity (HSI) on diffusion-weighted MRI (DWI), percentage of voxel using apparent diffusion coefficient value, and serum neuron-specific enolase levels. When replaced with HSI on DWI, the AUROC and sensitivity of the OHCA and CAHP models were 0.96 and 74.5% and 0.97 and 83.8%, respectively (100% specificity). Prognoses concerning neurologic outcomes improved compared with existing OHCA and CAHP models by adding new objective variables to replace no-flow time. External validation is required to generalize these results in various contexts.

Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy. The results indicated that luteolin induces the upregulation of the unfolded protein response pathway through the ER stress sensors, which helps as an influential regulator for the apoptosis pathway in PC12 cells. The results suggested that the understanding of the molecular mechanisms underlying luteolin‑induced apoptosis may be useful in cancer therapeutics, chemoprevention and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.

Objective Critically ill patients sometimes require transport to another location. Longer intra-hospital transport time increases the risk of hemodynamic instability and associated complications. Therefore, reducing intra-hospital transport time is critical. Our objective was to evaluate whether or not a new device the easy tube arrange device (ETAD) has the potential to reduce intra-hospital transport time of critically ill patients. Methods We enrolled volunteers for this prospective randomized controlled study. Each participant arranged four, five, and six fluid tubings, monitoring lines, and therapeutic equipment on a cardiopulmonary resuscitation training mannequin (Resusci Anne). The time required to arrange the fluid tubings for intra-hospital transport using two different methods was evaluated. Results The median time to arrange four, five, and six fluid tubings was 86.00 (76.50 to 98.50), 96.00 (86.00 to 113.00), and 115.50 (93.00 to 130.75) seconds, respectively, using the conventional method and 60.50 (52.50 to 72.75), 69.00 (57.75 to 80.80), and 72.50 (64.75 to 90.50) seconds using the ETAD (all P

Monoacylglycerol O-acyltransferase 2 (MOGAT2) plays critical roles in lipid homeostasis. We reported a cDNA designed BmMOGAT2 encoding an MOGAT2 homologue cloned from the fat body of the silkworm Bombyx mori, by using conserved domain homology search method. The resultant BmMOGAT2 was translated to a protein encoding 352 amino acids with a theoretical isoelectric point of 9.04 and a molecular weight of 39,944.48 Da. Homology analysis revealed that BmMOGAT2 exhibits higher similarity on the amino acid level to those of other species already reported; 48% identity with Homo sapiens, 46% with Mus musculus, 50% with Danio rerio, and 42% with Drosophila melanogaster. The expression of BmMOGAT2 was detected in all tissues tested with 2-fold higher expression in the post-silk gland, as compared to others, and stronger expression of the larval fat body at 1st instar, as compared with other stages. The BmMOGAT2 is a predicted endoplasmic reticulum (ER) transmembrane protein with two ER transmembrane domains; BmMOGAT2 gene expression increases in response to ER stress-inducible drugs. To our knowledge, this is the first report of Bombyx mori MOGAT2 cDNA, BmMOGAT2, and its associated molecular characterization.

OBJECTIVE We investigated whether patients with out-of-hospital cardiac arrest (OHCA) due to an acute myocardial infarction without cardiogenic shock required higher doses of vasopressors with low targeted temperature management (TTM) after return of spontaneous circulation. METHODS We included consecutive comatose patients resuscitated from OHCA between January 2011 and December 2013. Patients with return of spontaneous circulation, regional wall motion abnormality on echocardiography, and coronary artery stenosis of ≥70% on percutaneous coronary artery angiography were enrolled. These patients received 36°C TTM or 33°C TTM following approval of TTM by patients' next-of-kin (36°C and 33°C TTM groups, respectively). The cumulative vasopressor index was compared between groups. RESULTS During induction phase, dose of vasopressors did not differ between groups. In the maintenance phase, the norepinephrine dose was 0.37±0.57 and 0.26±0.91 µg·kg-1·min-1 in the 33°C and 36°C TTM groups, respectively (P

We examined whether combining biomarkers measurements and brain images early after the return of spontaneous circulation improves prognostic performance compared with the use of either biomarkers or brain images for patients with cardiac arrest following target temperature management (TTM). This retrospective observational study involved comatose out-of-hospital cardiac arrest survivors. We analyzed neuron-specific enolase levels in serum (NSE) or cerebrospinal fluid (CSF), grey-to-white matter ratio by brain computed tomography, presence of high signal intensity (HSI) in diffusion-weighted imaging (DWI), and voxel-based apparent diffusion coefficient (ADC). Of the 58 patients, 33 (56.9%) had poor neurologic outcomes. CSF NSE levels showed better prognostic performance (area under the curve (AUC) 0.873, 95% confidence interval (CI) 0.749&ndash, 0.950) than serum NSE levels (AUC 0.792, 95% CI 0.644&ndash, 0.888). HSI in DWI showed the best prognostic performance (AUC 0.833, 95% CI 0.711&ndash, 0.919). Combining CSF NSE levels and HSI in DWI had better prognostic performance (AUC 0.925, 95% CI 0.813&ndash, 0.981) than each individual method, followed by the combination of serum NSE levels and HSI on DWI and that of CSF NSE levels and the percentage of voxels of ADC (AUC 0.901, 95% CI 0.792&ndash, 0.965, AUC 0.849, 95% CI 0.717&ndash, 0.935, respectively). Combining CSF/serum NSE levels and HSI in DWI before TTM improved the prognostic performance compared to either each individual method or other combinations.

The present study aimed to compare the ventricular enhancement time between humeral intraosseous access (HIO) and brachial intravenous access (BIV) during cardiopulmonary resuscitation (CPR) in adult humans. To our knowledge, this is the first such study during CPR in adult humans.This prospective single-centre observational cohort study assessed the medical records of patients who underwent CPR between January 2018 and March 2018. The primary endpoints were the left and right ventricular enhancement (LVE and RVE, respectively) times after administration of a microbubble contrast agent via HIO or BIV. Continuous variables are reported as means and standard deviations depending on normal distribution, while categorical variables are reported as frequencies and percentages. The paired t-test and analysis of variance were used to compare HIO and BIV. Differences were considered significant at a P-value0.05.The study included 10 patients. The HIO time (15.60 ± 6.45 s) was significantly lower than the BIV time (20.80 ± 7.05 s; P = 0.009). The RVE time was significantly lower with HIO (5.60 ± 1.71 s) than with BIV (15.40 ± 3.24 s; P 0.001). Additionally, the LVE time was significantly lower with HIO (120.20 ± 4.18 s) than with BIV (132.00 ± 3.09 s; P 0.001).Our results indicated that the arrival times of a drug at the right and left ventricles are significantly lower with HIO than with BIV in an adult cardiac arrest model.

The effects of hypothermic treatment (32℃) on recovery from ischemia are controversial because the precise mechanisms of hypothermia remain unclear. We demonstrated previously that hypothermia induces beta-catenin-interacting protein 1 (CTNNBIP1) gene expression in vitro. In this study, we evaluated the effects of various hypothermic conditions, including lithium chloride treatment, on CTNNBIP1 gene expression. The results show that short-term hypothermic treatment resulted in relatively higher CTNNBIP1 gene expression than that of a longer treatment. These findings indicate that hypothermia controls CTNNBIP1 gene expression, which may provide clues to develop treatments to recover from and diagnose ischemia.

Clusterin (also known as apolipoprotein J) is a highly conserved glycoprotein involved in various biological processes, including attenuation of complement activity, sperm maturation, apoptosis, and reverse lipid transport. Although clusterin is reportedly associated with metabolic diseases, the metabolic regulation of clusterin expression is largely unknown. We investigated the effect of insulin on hepatic clusterin expression and its underlying mechanisms. Insulin increased the mRNA and protein levels of clusterin in primary hepatocytes and hepatoma cell lines. Serial deletion and mutant analysis of the clusterin promoter demonstrated that insulin-stimulated transactivation is mediated via a non-canonical E-box (NCE-box) motif in the proximal upstream region. Interestingly, sterol regulatory element binding protein-1c (SREBP-1c) co-transfection showed the same transactivation pattern as insulin stimulation in serial deletion and mutant promoter analysis. In contrast, co-transfection with a dominant negative form of SREBP-1c inhibited insulin-stimulated clusterin expression. Furthermore, insulin increased the recruitment of SREBP-1c to the NCE-box of the clusterin promoter region. Taken together, our results suggest that an NCE-box within the clusterin promoter is necessary for insulin-stimulated hepatic expression of clusterin via SREBP-1c.

There are several studies that show hypothermia improves cellular ischemia damages on experimental and clinical bases. However, its exact molecular mechanisms are unclear. In this study, we demonstrate that hypothermia induced insulin-like growth factor 1 (IGF1) gene expression, and its expression was dramatically decreased under ischemic insults. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both the phosphorylation of eIF2α (eukaryotic translation initiation factor 2 alpha) and ATF6 (activating transcription factor-6) proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. We suggest that hypothermia-treated IGF1 gene expression after ischemia may show a good possibility for the development of treatments and diagnostic methods in cerebral ischemic damages.

The endoplasmic reticulum (ER) in the eukaryotic cells is the f irst compartment in the secretory pathway. Almost secretory proteins and membrane proteins are secreted through the ER, in which post-translational modifications occur via diverse signals from the ER lumen to the cytoplasm and nucleus. Only then are correctly-folded proteins secreted to the outside cells. Unfolded proteins that accumulate in the ER cause a kind of intracellular stress, ER s tress, and activate an unfolded protein response (UPR) system. The 3 major transducers of the UPR are inositol requiring 1 (IRE1), PKR-like ER kinase (PERK) and activating transcription factor 6 (ATF6), all of which are ER transmembrane proteins. Recently, novel types of a new ATF6 family have been identified. Those commonly have an ER-transmembrane domain, a transcription-activation domain and a basic leucine zipper (bZIP) do- main―Luman, OASIS, BBF2H7, CREBH and CREB4. Each factor functions by regulating the UPR in specific organs and tissues. Alth ough the detailed molecular mechanisms of OASIS family members are unknown, in this study we comprehensively introduce these molecular signals.

In this study, we show that INS-1 pancreatic β-cells treated for 2 h with hemolymph of larvae of rhinoceros beetle, Allomyrina dichotoma, secreted about twice as much insulin compared to control cells without such treatment. Activating transcription factor 3 (ATF3) was the highest upregulated gene in DNA chip analysis. The A. dichotoma hemolymph dose-dependently induced increased expression levels of genes encoding ATF3 and insulin. Conversely, treatment with ATF3 siRNA inhibited expression levels of both genes and curbed insulin secretion. These results suggest that the A. dichotoma hemolymph has potential for treating and preventing diabetes or diabetes-related complications.

Although an endoplasmic reticulum (ER) induction by calcium-channel blocker has been reported, the mechanism of ER stress-mediated apoptosis by nicardipine is unknown. Here, we demonstrated induction of apoptosis by nicardipine in PC12 cells. It was accompanied by the formation of apoptotic bodies via activation of ER-stress sensor, inositol-requiring enzyme 1 (IRE1). IRE1 induces the downregulation of key anti-apoptotic Bcl-2 expression in apoptosis. However, the altered expression of ER chaperones was not observed following nicardipine treatment. The results suggest that insight into the molecular mechanisms underlying nicardipineinduced apoptosis may facilitate the reduction of side effects and active treatment.

Purpose: To investigate and analyse the role of practice-assisting manpower in the emergency care centers of teaching hospitals for more efficient allocation of the workload in hospitals to provide better medical care. Methods: We enrolled a total of eight practice-assisting manpower in four emergency care centers of teaching hospitals located in Daejeon Metropolitan City and Chungcheong Province areas. The current demographics and conditions of practice-assisting manpower and their work schedules were surveyed and collected. Board-certified emergency physicians from each hospital observed tasks performed by practice-assisting manpower for 60 minutes during both day and night shifts, and data collected were analysed by time-motion study method. Results: The practice-assisting manpower participants were of certified first-ranked Emergency Medical Technician (EMT). The mean working hours per week were 42.5 ± 3.3 h. The total number of performed tasks during the study period was 275 items (day shift: 141, night shift: 134) in total observation time. Tasks performed were divided into three categories: procedure-assisting (87 items), treatment-assisting (169 items), and personal activities (19 items). The time consumed for procedure-assisting tasks, treatment-assisting tasks, and personal activities were recorded as 8 h 35 min 47 s, 4 h 27 min 41 s, and 2 h 56 min 32 s, relatively. Conclusion: Though some items in both procedure-assisting and treatment-assisting tasks were classified as beyond the scope of work of EMT, it is observed that the role of practice-assisting manpower in emergency care is critical and significant for efficient patient care in the emergency care settings. This further suggests reconsidering the functions of practice-assisting manpower and reallocates duties among the workforce of emergency medical service providers for the present and future.