SNP Diagnosis in Elite Athletes by Korean Athletic Performance

PURPOSE The purpose of this study is to analyze SNPs related to performance (maximal strength vs. cardiovascular endurance) of world-class Korean elite athletes using the Genome-Wide Human SNP Array 6.0 and to determine genotypes related to maximal strength and cardiovascular endurance performance that are unique to “ Koreans”. METHODS Using the Genome-Wide Human SNP Array 6.0, we analyzed SNPs obtained from 54 world-class Korean elite athletes (Olympic participants/World Championship medalists). The group was divided into the 16 maximal strength group (12 males and 4 females weightlifters who had won medals at the Olympic and World Championships), 12 cardiovascular endurance group (12 males marathon runners who had run within 2 hours and 12 minutes in international competitions), and 26 individuals from the general population (25 males and 1 female). All the obtained SNPs were subjected to quality control (QC), and a total of 867,982 SNPs were analyzed between the marathon runners and general population subjects (641,040 SNPs) and between weightlifters and general population subjects (634,418 SNPs). RESULTS The number of SNPs with more than two SNPs within 100 kb, which satisfied the threshold of sample QC and significance level of p<.0001, was 60 in marathoners and 18 in weightlifters compared to the general population subjects. When the genomic features of SNPs of each performance trait were analyzed, the 60 SNPs for cardiovascular endurance with two or more SNPs within 100 kb that met the p<.0001 threshold for significance were distributed across 15 regions, and the 18 SNPs for maximal strength were distributed across 7 regions. CONCLUSIONS In conclusion, SNPs related to cardiovascular endurance and maximal strength suggest the possibility of producing gene chips to derive genotypes unique to “ Koreans” in the future. Additionally, this study provides important basic data for further research

Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury

Overproduction of hydrogen peroxide (H2O2) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H2O2-activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti-inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H2O2 and release HBA (p-hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H2O2-stimulated cells by suppressing the generation of ROS and pro-inflammatory cytokines. In mouse models of hepatic I/R and cardiac I/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H2O2-scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H2O2-activatable antioxidant prodrug for the treatment of I/R injuries

Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

<p>Abstract</p> <p>Background</p> <p>A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX).</p> <p>Methods</p> <p>We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells.</p> <p>Results</p> <p>We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. <it>In vitro </it>invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells.</p> <p>Conclusions</p> <p>We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in the Cox-2-induced invasion of MCF-7/DOX cells. Therefore, not only Cox-2 but also EP1 and EP3 could be important targets for chemosensitization and inhibition of metastasis in breast cancers that are resistant to chemotherapy.</p

Understanding of Ovarian Cancer Cell-Derived Exosome Tropism for Future Therapeutic Applications

Exosomes, a subtype of extracellular vesicles, ranging from 50 to 200 nm in diameter, and mediate cell-to-cell communication in normal biological and pathological processes. Exosomes derived from tumors have multiple functions in cancer progression, resistance, and metastasis through cancer exosome-derived tropism. However, there is no quantitative information on cancer exosome-derived tropism. Such data would be highly beneficial to guide cancer therapy by inhibiting exosome release and/or uptake. Using two fluorescent protein (mKate2) transfected ovarian cancer cell lines (OVCA4 and OVCA8), cancer exosome tropism was quantified by measuring the released exosome from ovarian cancer cells and determining the uptake of exosomes into parental ovarian cancer cells, 3D spheroids, and tumors in tumor-bearing mice. The OVCA4 cells release 50 to 200 exosomes per cell, and the OVCA8 cells do 300 to 560 per cell. The uptake of exosomes by parental ovarian cancer cells is many-fold higher than by non-parental cells. In tumor-bearing mice, most exosomes are homing to the parent cancer rather than other tissues. We successfully quantified exosome release and uptake by the parent cancer cells, further proving the tropism of cancer cell-derived exosomes. The results implied that cancer exosome tropism could provide useful information for future cancer therapeutic applications

Introduction of Infection Prevention Tracheal Intubation Protocol during the COVID-19 Pandemic Is Not Associated with First-Pass Success Rates of Endotracheal Intubation in the Emergency Department: A Before-and-After Comparative Study

Aerosols and droplets have put healthcare workers performing airway management at high risk of contracting coronavirus disease 2019 (COVID-19). Experts have developed endotracheal intubation (ETI) guidelines and protocols to protect intubators from infection. We aimed to determine whether changes in the emergency department (ED) intubation protocol to prevent COVID-19 infection were associated with first-pass success (FPS) rates in ETI. We used data from the airway management registries in two academic EDs. The study was divided into pre-pandemic (January 2018 to January 2020) and pandemic (February 2020 to February 2022) periods. We selected 2476 intubation cases, including 1151 and 1325 cases recorded before and during the pandemic, respectively. During the pandemic, the FPS rate was 92.2%, which did not change significantly, and major complications increased slightly but not significantly compared with the pre-pandemic period. The OR for the FPS of applying infection prevention intubation protocols was 0.72 (p = 0.069) in a subgroup analysis, junior emergency physicians (PGY1 residents) had an FPS of less than 80% regardless of pandemic protocol implementation. The FPS rate of senior emergency physicians in physiologically difficult airways decreased significantly during the pandemic (98.0% to 88.5%). In conclusion, the FPS rate and complications for adult ETI performed by emergency physicians using COVID-19 infection prevention intubation protocols were similar to pre-pandemic conditions

Hydrogen Peroxide‐Responsive Nanoparticle Reduces Myocardial Ischemia/Reperfusion Injury

Background: During myocardial ischemia/reperfusion (I/R), a large amount of reactive oxygen species (ROS) is produced. In particular, overproduction of hydrogen peroxide (H2O2) is considered to be a main cause of I/R‐mediated tissue damage. We generated novel H2O2‐responsive antioxidant polymer nanoparticles (PVAX and HPOX) that are able to target the site of ROS overproduction and attenuate the oxidative stress‐associated diseases. In this study, nanoparticles were examined for their therapeutic effect on myocardial I/R injury. Methods and Results: The therapeutic effect of nanoparticles during cardiac I/R was evaluated in mice. A single dose of PVAX (3 mg/kg) showed a significant improvement in both cardiac output and fraction shortening compared with poly(lactic‐coglycolic acid) (PLGA) particle, a non‐H2O2‐activatable nanoparticle. PVAX also significantly reduced the myocardial infarction/area compared with PLGA (48.7±4.2 vs 14.5±2.1). In addition, PVAX effectively reduced caspase‐3 activation and TUNEL‐positive cells compared with PLGA. Furthermore, PVAX significantly decreased TNF‐α and MCP‐1 mRNA levels. To explore the antioxidant effect of PVAX by scavenging ROS, dihydroethidium staining was used as an indicator of ROS generation. PVAX effectively suppressed the generation of ROS caused by I/R, whereas a number of dihydroethidium‐positive cells were observed in a group with PLGA I/R. In addition, PVAX significantly reduced the level of NADPH oxidase (NOX) 2 and 4 expression, which favors the reduction in ROS generation after I/R. Conclusions: Taken together, these results suggest that H2O2‐responsive antioxidant PVAX has tremendous potential as a therapeutic agent for myocardial I/R injury

Recurrent Pulseless Ventricular Tachycardia Induced by Commotio Cordis Treated with Therapeutic Hypothermia

The survival rate of commotio cordis is low, and there is often associated neurological disability if return of spontaneous circulation (ROSC) can be achieved. We report a case of commotio cordis treated with therapeutic hypothermia (TH) that demonstrated a favorable outcome. A 16-year-old female was transferred to our emergency department (ED) for collapse after being struck in the chest with a dodgeball. She has no history of heart problems. She was brought to our ED with pulseless ventricular tachycardia (VT), and ROSC was achieved with defibrillation. She was comatose at our ED and was treated with TH at a target temperature of 33°C for 24 hours. After transfer to the intensive care unit, pulseless VT occurred, and defibrillation was performed twice. She recovered to baseline neurologic status with the exception of some memory difficulties

The Prognostic Value of Optic Nerve Sheath Diameter/Eyeball Transverse Diameter Ratio in the Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients

Background and objectives: The optic nerve sheath diameter (ONSD) is indicative of elevated intracranial pressure. However, the usefulness of the ONSD for predicting neurologic outcomes in cardiac arrest survivals has been debatable. Reportedly, the ONSD/eyeball transverse diameter (ETD) ratio is a more reliable marker for identifying intracranial pressure than sole use of ONSD. Materials and Methods: This retrospective study aimed to investigate the prognostic value of the ONSD/ETD ratio in out-of-hospital cardiac arrest (OHCA) patients. We studied the brain computed tomography scans of adult OHCA patients with return of spontaneous circulation, who visited a single hospital connected with a Korean university between January 2015 and September 2020. We collected baseline characteristics and patient information from electronic medical records and ONSD and ETD were measured by two physicians with a pre-defined protocol. According to their neurologic outcome upon hospital discharge, patients were divided into good neurologic outcome (GNO; cerebral performance category [CPC] 1&ndash;2) and poor neurologic outcome (PNO; CPC 3&ndash;5) groups. We evaluated the ONSD/ETD ratio between the GNO and PNO groups to establish its prognostic value for neurologic outcomes. Results: Of the 100 included patients, 28 had GNO. Both the ONSD and ETD were not significantly different between the two groups (ONSD, 5.48 mm vs. 5.66 mm, p = 0.054; ETD, 22.98 mm vs. 22.61 mm, p = 0.204). However, the ONSD/ETD ratio was significantly higher in the PNO group in the univariate analysis (0.239 vs. 0.255, p = 0.014). The area under the receiver operating characteristic curve of ONSD/ETD ratio for predicting PNO was 0.66 (95% confidence interval, 0.56&ndash;0.75; p = 0.006). There was no independent relationship between the ONSD/ETD ratio and PNO in multivariate analysis (aOR = 0.000; p = 0.173). Conclusions: The ONSD/ETD ratio was more reliable than sole use of ONSD and might be used to predict neurologic outcomes in OHCA survivors

Comparisons of the Pentax-AWS, Glidescope, and Macintosh Laryngoscopes for Intubation Performance during Mechanical Chest Compressions in Left Lateral Tilt: A Randomized Simulation Study of Maternal Cardiopulmonary Resuscitation

. Purpose. Rapid advanced airway management is important in maternal cardiopulmonary resuscitation (CPR). This study aimed to compare intubation performances among Pentax-AWS (AWS), Glidescope (GVL), and Macintosh laryngoscope (MCL) during mechanical chest compression in 15 ∘ and 30 ∘ left lateral tilt. Methods. In 19 emergency physicians, a prospective randomized crossover study was conducted to examine the three laryngoscopes. Primary outcomes were the intubation time and the success rate for intubation. Results. The median intubation time using AWS was shorter than that of GVL and MCL in both tilt degrees. The time to visualize the glottic view in GVL and AWS was significantly lower than that of MCL (all &lt; 0.05), whereas there was no significant difference between the two video laryngoscopes (in 15 ∘ tilt, = 1; in 30 ∘ tilt, = 0.71). The progression of tracheal tube using AWS was faster than that of MCL and GVL in both degrees (all &lt; 0.001). Intubations using AWS and GVL showed higher success rate than that of Macintosh laryngoscopes. Conclusions. The AWS could be an appropriate laryngoscope for airway management of pregnant women in tilt CPR considering intubation time and success rate

Comparison of the Pentax Airwayscope, Glidescope Video Laryngoscope, and Macintosh Laryngoscope During Chest Compression According to Bed Height

We aimed to investigate whether bed height affects intubation performance in the setting of cardiopulmonary resuscitation and which type of laryngoscope shows the best performance at each bed height. A randomized crossover manikin study was conducted. Twenty-one participants were enrolled, and they were randomly allocated to 2 groups: group A (n = 10) and group B (n = 11). The participants underwent emergency endotracheal intubation (ETI) using the Airwayscope (AWS), Glidescope video laryngoscope, and Macintosh laryngoscope in random order while chest compression was performed. Each ETI was conducted at 2 levels of bed height (minimum bed height: 68.9 cm and maximum bed height: 101.3 cm). The primary outcomes were the time to intubation (TTI) and the success rate of ETI. The P value for statistical significance was set at 0.05 and 0.017 in post-hoc test. The success rate of ETI was always 100% regardless of the type of laryngoscope or the bed height. TTI was not significantly different between the 2 bed heights regardless of the type of laryngoscope (all P &gt; 0.05). The time for AWS was the shortest among the 3 laryngoscopes at both bed heights (13.7 +/- 3.6 at the minimum bed height and 13.4 +/- 4.7 at the maximum bed height) (all P &lt; 0.017). The TTI of Glidescope video laryngoscope was not significantly shorter than that of Macintosh laryngoscope at the minimum height (17.6 +/- 4.0 vs 19.6 +/- 4.8; P = 0.02). The bed height, whether adjusted to the minimum or maximum setting, did not affect intubation performance. In addition, regardless of the bed height, the intubation time with the video laryngoscopes, especially AWS, was significantly shorter than that with the direct laryngoscope during chest compression.This research was supported by the Civil research projects for solving social problems through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2015M3C8A7A02027410)