Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling.

Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP-60/HSPD1, a major mitochondrial chaperone, boosts anti-bacterial immunity through the up-regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP-60 is necessary and sufficient to increase resistance to PA14. We show that HSP-60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti-bacterial immune pathway, is down-regulated by genetic inhibition of hsp-60, and up-regulated by increased expression of hsp-60 Overexpression of HSPD1, the mammalian ortholog of hsp-60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol-localized HSP-60 physically binds and stabilizes SEK-1/MAP kinase kinase 3, which in turn up-regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up-regulating cytosolic p38 MAPK signaling.

Fabrication of a Micro/Nano-Net Membrane Using Cellulose Nanocrystals Derived from Seaweed.

We have successfully extracted cellulose nanocrystals (CNCs) from seaweed by removing unwanted materials via our modified process. The prepared CNCs were mixed with two biocompatible polymers (polyethylene oxide (PEO)/Eudragit S100). We used the most popular electrospinning method to fabricate a micro/nano-net membrane. The formation of nano-webs between fundamental micro/nanofibers was observed via SEM and TEM, according to the mixing ratio of the solution (PEO:Eudragit: 1:1, 2:1, 3:1 wt:wt%) with 0, 5, 10% CNCs per polymer weight. We found the optimal condition to fabricate nano-net in the membrane and expect it to be applicable for wound healing, tissue engineering, and various filter applications.

Preliminary Study for Measurement of Shear Stress and Hemocompatibility Using Commercialized Lab on a Chip.

We have investigated the effect of flow rate on shear stress and in turn thrombus formation on a lab-on-a-chip with a microchannel that is suitable for cell culture and growth. Using a combination of Arduino UNO, Arduino Motor Shield, and a SERVO stepper motor, we created a pump system that closely mimics the in vivo conditions of the human body. With this system, we achieved continuous flow of blood and observed attached platelets at the bottom of the collagen coated microslide, confirming that with shear stress, thrombus formation increases.

Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival. METHODS: This prospective observational study and retrospective review included adult out-of-hospital cardiac arrest survivors who were treated by hypothermia-targeted temperature management. Serum NGAL was assessed at 0, 24, 48, and 72h after return of spontaneous circulation. The primary outcome was poor outcome at six months after cardiac arrest, defined as cerebral performance category score of 3-5. The secondary outcome was six-month mortality. RESULTS: In total, 76 patients were analyzed. The patients with poor outcomes showed significantly higher NGAL levels at 24, 48 and 72h after cardiac arrest than the patients with good outcomes. Long-term survival rates were significantly lower in the high-NGAL group than in the low-NGAL group at each time point. Subgroup analysis of patients who survived 72h showed that only serum NGAL 72h after cardiac arrest had prognostic value for long-term outcomes (area under the receiver operating characteristic curve=0.72; p=0.02). CONCLUSIONS: Post-cardiac arrest serum NGAL is associated with long-term outcomes and survival; particularly, three days post-cardiac arrest is the optimal time point for predicting long-term outcomes. However, the predictive power of NGAL is unsatisfactory, and it should be regarded as an additional prognostic modality.

A Wireless ExG Interface for Patch-Type ECG Holter and EMG-Controlled Robot Hand.

This paper presents a wearable electrophysiological interface with enhanced immunity to motion artifacts. Anti-artifact schemes, including a patch-type modular structure and real-time automatic level adjustment, are proposed and verified in two wireless system prototypes of a patch-type electrocardiogram (ECG) module and an electromyogram (EMG)-based robot-hand controller. Their common ExG readout integrated circuit (ROIC), which is reconfigurable for multiple physiological interfaces, is designed and fabricated in a 0.18 µm CMOS process. Moreover, analog pre-processing structures based on envelope detection are integrated with one another to mitigate signal processing burdens in the digital domain effectively.

Traumatic lumbar artery rupture after lumbar spinal fracture dislocation causing hypovolemic shock: An endovascular treatment.

Recently, we observed a case of lumbar artery injury after trauma, which was treated by endovascular embolization. A 67-year-old woman who was injured in a traffic accident was brought to the emergency room. She was conscious and her hemodynamic condition was stable, but she had paraplegia below L1 dermatome. Contrast-enhanced computed tomography scan of abdomen and pelvis revealed fracture dislocation of L3/4 along with retroperitoneal hematomas. However, there was no evidence of traumatic injury in both thoracic and abdominal cavity. At that time, her blood pressure suddenly decreased to 60/40 mmHg and her mental status deteriorated. Also, her hemoglobin level was 5.4 g/dl. While her hemodynamic condition stabilized with massive fluid resuscitation including blood transfusion, an angiography was immediately performed to look for and embolize site of retroperitoneal hemorrhage. On the angiographic images, there was an active extravasation from ruptured left 3rd lumbar artery, and we performed complete embolization with GELFOAM and coil. Lumbar artery injury after trauma is rare and endovascular treatment is useful in case of hemodynamic instability.

Identification of co-occurring transcription factor binding sites from DNA sequence using clustered position weight matrices.

Accurate prediction of transcription factor binding sites (TFBSs) is a prerequisite for identifying cis-regulatory modules that underlie transcriptional regulatory circuits encoded in the genome. Here, we present a computational framework for detecting TFBSs, when multiple position weight matrices (PWMs) for a transcription factor are available. Grouping multiple PWMs of a transcription factor (TF) based on their sequence similarity improves the specificity of TFBS prediction, which was evaluated using multiple genome-wide ChIP-Seq data sets from 26 TFs. The Z-scores of the area under a receiver operating characteristic curve (AUC) values of 368 TFs were calculated and used to statistically identify co-occurring regulatory motifs in the TF bound ChIP loci. Motifs that are co-occurring along with the empirical bindings of E2F, JUN or MYC have been evaluated, in the basal or stimulated condition. Results prove our method can be useful to systematically identify the co-occurring motifs of the TF for the given conditions.

Proteomic evaluation to identify biomarkers for carpal tunnel syndrome: a comparative serum analysis.

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment, causing pain, impairment, and disability. To identify proteins of CTS comprehensively, a comparative serum analysis of CTS patients and normal control subjects was performed. The two-dimensional electrophoresis patterns of serum obtained from six CTS patients and six normal control subjects were compared. We found 10 proteins that were significantly altered in the serum of CTS patients, among which four were upregulated and six were downregulated. The upregulated spots were identified as Chain A, heat shock 70-kDa protein, 42-kDa ATPase N-terminal domain; glutathione-insulin transhydrogenase (216AA); cAMP-dependent protein kinase inhibitor alpha; and mutant ß-globin. The downregulated spots were identified as vitamin D-binding protein (VDBP), fibrinogen gamma chain, apolipoprotein A-IV (ApoA-IV), clusterin, heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), and one unidentified protein. The information obtained from this proteomic analysis will be very useful in understanding the pathophysiology of CTS and in finding suitable proteins that can serve as new diagnostic biomarkers of CTS.

Combination treatment with 17ß-estradiol and therapeutic hypothermia for transient global cerebral ischemia in rats.

OBJECTIVE: Therapeutic hypothermia is now regarded as the only effective treatment of global ischemic injury after cardiac arrest. Numerous studies of the neuroprotective effects of 17ß-estradiol have yielded conflicting results depending on administration route and dose. Herein, we investigated the neuroprotective effect of postischemic 17ß-estradiol administration combined with therapeutic hypothermia. METHODS: Twenty-one rats were randomly divided into 4 groups: control (group I), therapeutic hypothermia (group II), 17ß-estradiol treatment (group III), and therapeutic hypothermia combined with 17ß-estradiol treatment (group IV). One rat was assigned to a sham operation group. With the exception of the sham-operated rat, all animals underwent transient global cerebral ischemia for 20 minutes by the 4-vessel occlusion method. Hypothermia was maintained at 33°C for 2 hours in groups II and IV, and 17ß-estradiol (10 µg/kg) was intraperitoneally administered to rats in groups III and IV. Neurologic deficit scores and hippocampal cornu ammonis 1 neuronal injury were assessed 72 hours postischemia. RESULTS: The neurologic deficit score was not significantly different among the groups. The percentage of normal neurons in the hippocampal cornu ammonis 1 was 7.32% ± 0.88% in group I, 53.65% ± 2.52% in group II, 51.6% ± 3.44% in group III, and 79.79% ± 1.6% in group IV. The neuroprotective effect in the combined treatment group was markedly greater than in the single treatment groups, which suggests that hypothermia and 17ß-estradiol work synergistically to exert neuroprotection. CONCLUSION: Postischemic administration of low-dose 17ß-estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.

Therapeutic hypothermia complicated by spontaneous brain stem hemorrhage.

Hypothermia increases clotting time, which is known as hypothermic coagulopathy. However, prothrombin time and activated partial thromboplastin time prolongation associated with therapeutic hypothermia is usually mild and thus, hypothermic coagulopathy is not considered to cause clinically significant bleeding. On the other hand, PT and aPTT do not seem to reflect the severity of hypothermic coagulopathy. Serious bleeding complications of therapeutic hypothermia has not been reported previously. Herein, we introduce a case of spontaneous brain stem hemorrhage as a complication of therapeutic hypothermia-induced coagulopathy.

An Unusual Case of Traumatic Cervical Epidural Hematoma in an Infant.

Spinal epidural hematoma (SEH) is exceedingly rare, especially in children. Acute cervical epidural hematoma presents suddenly, with progressive neurologic deficits. However, it is difficult to diagnose in infants, which results in delayed diagnosis. We report a case of rapid diagnosis of traumatic cervical epidural hematoma in an infant with successful hematoma evacuation. An 11-month-old patient was brought to the emergency department after falling backward from a o30cm-high bed. The child, who previously was able to stand without support, could not stand alone and frequently fell prone when he sat down. The brain magnetic resonance imagingshowed no abnormalities. On the spinal MRI, an acute epidural hematoma located at the C3-T1 level and pressed against the spinal cord was confirmed. Three months after surgical evacuation, the Korean version of the Bayley Scales of Infant and Toddler Development -III (K-Bayley-III) assessment was performed, and a developmental quotient (DQ) of 95 or higher was demonstrated for all parameters, including motor functions. This report described an exceedingly rare case of acute cervical epidural hematoma in an infant, induced by trauma. The diagnosis and treatment were performed within one day of injury. This process was significantly faster than other reported infantile cases of cervical epidural hematoma, which were diagnosed within 4 days to 2 months.

Moyamoya syndrome following growth hormone-secreting pituitary adenoma.

We report a case of Moyamoya syndrome developing in association with growth hormone-secreting pituitary adenoma. A 31-year-old female presented with acromegalic features. Magnetic resonance imaging revealed a 1 × 2 cm tumor in the sella turcica and MR angiography demonstrated unremarkable findings. Blood growth hormone and insulin-like growth factor I levels were elevated to 74.1 ng/ml and over 1 575 ng/ml, respectively. The diagnosis was growth hormone-secreting pituitary adenoma, and the tumor was removed through a transsphenoidal approach. Four years after surgery, she visited the outpatient department due to left side weakness for 2 months. Magnetic resonance images showed acute and old infarcted lesions in the basal ganglia and subcortical area and residual small pituitary adenoma in the sellar area. MR angiography demonstrated stenosis of the bilateral distal internal carotid arteries with basal collateral vessels. Conventional cerebral angiography showed complete obstruction in the right internal carotid artery and severe stenosis of the left internal carotid artery, middle cerebral artery, and anterior cerebral artery with basal collateral vessels. Her blood growth hormone and insulin-like growth factor I levels were 15.3 ng/ml and 1 055 ng/ml, respectively. We believe that excess systemic exposures of growth hormone and insulin-like growth factor I may participate in the development of Moyamoya syndrome.

A simulation-based continuing professional development course for the first 5 minutes of cardiac arrest in the resource-limited local clinics.

PURPOSE: Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. METHODS: Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant's responses to the course using a questionnaire. RESULTS: During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. CONCLUSION: A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.

Fabrication of conductive silver paste recovered from leaching of waste catalyst using hydrochloric acid.

Transition metal compounds based on silver (Ag) and palladium (Pd) are extensively used as catalysts in the petrochemical industries. The catalytic activities of Ag and Pd decrease over time and hence need to be discarded. The recovery of elements like Ag from waste catalyst is essential because of its limited availability and cost, and it is environmentally beneficial with regards to recycling. In this study, Pd and Ag were leached from waste catalyst providing an alternative source suitable for a Ag paste electrode. Through an efficient reduction process, AgCl particles were obtained which serve as a precursor to synthesize Ag using ammonia as the solvent. The obtained Ag was fabricated to Ag paste by using mixed dispersion and solvent. The electrical resistivity of the Ag paste was recorded as 6.14 µΩ cm at 417 °C in a hydrogen atmosphere.

Comparing Door-To-Balloon Time between ST-Elevation Myocardial Infarction Electrocardiogram and Its Equivalents.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (pPCI), longer door-to-balloon (DTB) time is known to be associated with an unfavorable outcome. A percentage of patients with acute coronary occlusion present with atypical electrocardiographic (ECG) findings, known as STEMI-equivalents. We investigated whether DTB time for STEMI-equivalent patients was delayed. METHODS: This is a retrospective study including patients arriving at an emergency department with the acute coronary syndrome in whom emergent pPCI was performed. ECGs were classified into STEMI and STEMI-equivalent groups. We compared DTB time, with its components, between the groups. We also investigated whether STEMI-equivalent ECG was an independent predictor of DTB time delayed for more than 90 min. RESULTS: A total of 180 patients were included in the present study, and 23 patients (12.8%) presented with STEMI-equivalent ECGs. DTB time was significantly delayed in patients with STEMI-equivalent ECGs (89 (80-122) vs. 81 (70-88) min, p = 0.001). Multivariable logistic regression analysis showed that STEMI-equivalent ECG was an independent predictor of delayed DTB time (odds ratio: 4.692; 95% confidence interval: 1.632-13.490, p = 0.004). CONCLUSIONS: DTB time was significantly delayed in patients presenting with STEMI-equivalent ECGs. Prompt recognition of STEMI-equivalent ECGs by emergency physicians and interventional cardiologists might reduce DTB time and lead to a better clinical outcome.

Calcineurin, Calcium-Dependent Serine-Threonine Phosphatase Activation by Prion Peptide 106-126 Enhances Nuclear Factor-κB-Linked Proinflammatory Response through Autophagy Pathway.

Prion diseases are mortal neurodegenerative pathologies that are caused by the accumulation of abnormal prion protein (PrPSc) in the brain. Recent advances reveal that calcineurin may play a critical role in regulating nuclear factor kappa B (NF-κB) in the calcium-calmodulin pathway. However, the exact mechanism by calcineurin remains unclear. In the present study, we observed that the prion peptide induces calcineurin and autophagy activation. Also, NF-κB and proinflammatory cytokines like interleukin (IL)-6 and tumor necrosis factor (TNF)-α are upregulated upon exposure to prion peptide in human neuroblastoma. The results show that the prion peptide induces calcineurin activation, leading to the activation of NF-κB transcription factor via autophagy signaling. Expression of TNF-α and IL-6 was increased by calcineurin activation and blocked by calcineurin inhibitor and autophagy inhibitor treatments. Collectively, these findings indicate that calcineurin activation mediated by prion protein induces NF-κB-driven neuroinflammation via autophagy pathway, suggesting that calcineurin and autophagy may be possible therapeutic targets for neuroinflammation in neurodegeneration diseases including prion disease.

HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model.

It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model. However, neuroprotective mechanisms of such combined treatment of valproic acid with hypothermia remains unclear. We hypothesized that epigenetic regulation of HSP70 by histone acetylation could increase HSP70-mediated neuroprotection suppressed under hypothermia. Male Sprague-Dawley rats that achieved return of spontaneous circulation (ROSC) from asphyxial cardiac arrest were randomized to four groups: normothermia (37°C ± 1°C), hypothermia (33°C ± 1°C), normothermia + VPA (300 mg/kg IV initiated 5 minutes post-ROSC and infused over 20 min), and hypothermia + VPA. Three hours after ROSC, acetyl-histone H3 was highly expressed in VPA-administered groups (normothermia + VPA, hypothermia + VPA). Four hours after ROSC, HSP70 mRNA expression levels were significantly higher in normothermic groups (normothermia, normothermia + VPA) than in hypothermic groups (hypothermia, hypothermia + VPA). The hypothermia + VPA group showed significantly higher HSP70 mRNA expression than the hypothermia group. Similarly, at five hours after ROSC, HSP70 protein levels were significantly higher in normothermic groups than in hypothermic groups. HSP70 levels were significantly higher in the hypothermia + VPA group than in the hypothermia group. Only the hypothermia + VPA group showed significantly attenuated cleaved caspase-9 levels than the normothermia group. Hypothermia can attenuate the expression of HSP70 at transcriptional level. However, VPA administration can induce hyperacetylation of histone H3, leading to epigenetic transcriptional activation of HSP70 even in a hypothermic status. Combining VPA treatment with hypothermia may compensate for reduced activation of HSP70-mediated anti-apoptotic pathway.

Endotracheal intubation using a GlideScope video laryngoscope by emergency physicians: a multicentre analysis of 345 attempts in adult patients.

OBJECTIVE: To investigate the use and success rates of the GlideScope (GVL) by emergency physicians (EPs) during the initial two years after its introduction. METHODS: We performed an observational study using registry data of five emergency departments. The success rates in adult patients were evaluated and compared with those of conventional laryngoscope (CL). RESULTS: The GVL was used in 345 (10.7%) of 3233 intubation attempts by EPs. The overall success rate of the GVL was not higher than a CL (79.1% vs 77.6%, p=0.538). The success rate for the patients with difficult airway was higher in the GVL than a CL (80.0% vs 50.4%, p<0.001). CONCLUSION: The GVL was not used frequently by EPs during the initial two years after its introduction. Although the GVL provides a better glottic view, the overall success rates were similar to a CL. The GVL may be useful in patients with difficult airway.

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.

BACKGROUND: Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. METHODS: This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 µg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia. RESULTS: Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01). CONCLUSIONS: Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.

High HbA1c is associated with decreased 6-month survival and poor outcomes after out-of-hospital cardiac arrest: a retrospective cohort study.

BACKGROUND: To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-hospital cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM). METHODS: This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3-5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modeling were used for data analysis. RESULTS: Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%, p < 0.001) and 6-month outcomes (89.2% vs. 73.0%, p = 0.001) than the non-high HbA1c group. Kaplan-Meier analysis and the log-rank test showed that the survival time was significantly shorter in the patients with HbA1c > 6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c > 6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26-15.12, p < 0.001) and poor outcomes (OR 4.18, 95% CI 1.41-12.40, p < 0.001). CONCLUSIONS: This study showed that HbA1c higher than 6% at admission was associated with increased 6-month mortality and poor outcomes in OHCA survivors treated with hypothermic TTM. Poor long-term glycemic management may have prognostic significance after cardiac arrest.