1.Use of Darunavir-Cobicistat as a Treatment Option for Critically Ill Patients with SARS-CoV-2 Infection
Eun Jin KIM ; Sun Ha CHOI ; Jae Seok PARK ; Yong Shik KWON ; Jaehee LEE ; Yeonjae KIM ; Shin Yup LEE ; Eun Young CHOI
Yonsei Medical Journal 2020;61(9):826-830
We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who wereadmitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receivedarunavir-cobicistat (800–150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 receivedother antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and thecrude mortality rate of all patients in the darunavir-cobicistat group was lower than that in the controls [odds ratio (OR) 0.20, 95%confidence interval (CI) 0.04–0.89, p=0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistatgroup, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortalitythan the controls (OR 0.07, 95% CI 0.01–0.52, p=0.009). In conclusion, darunavir-cobicistat therapy was found to be associatedwith a significant survival benefit in critically ill patients with SARS-CoV-2 infection.
2.The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung KIM ; Jae-Han JEON ; Sung-Woo KIM ; Jun Sung MOON ; Nan Hee CHO ; Eugene HAN ; Ji Hong YOU ; Ji Yeon LEE ; Miri HYUN ; Jae Seok PARK ; Yong Shik KWON ; Yeon-Kyung CHOI ; Ki Tae KWON ; Shin Yup LEE ; Eon Ju JEON ; Jin-Woo KIM ; Hyo-Lim HONG ; Hyun Hee KWON ; Chi Young JUNG ; Yin Young LEE ; Eunyeoung HA ; Seung Min CHUNG ; Jian HUR ; June Hong AHN ; Na-young KIM ; Shin-Woo KIM ; Hyun Ha CHANG ; Yong Hoon LEE ; Jaehee LEE ; Keun-Gyu PARK ; Hyun Ah KIM ; Ji-Hyun LEE
Diabetes & Metabolism Journal 2020;44(4):602-613
Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. Compared with the non-DM group ( DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.
3.Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo
Sehwan KIM ; Gyeong Joon MOON ; Yong Seok OH ; Jungha PARK ; Won Ho SHIN ; Jae Yeong JEONG ; Kwang Shik CHOI ; Byung Kwan JIN ; Nikolai KHOLODILOV ; Robert E BURKE ; Hyung Jun KIM ; Chang Man HA ; Seok Geun LEE ; Sang Ryong KIM
Experimental & Molecular Medicine 2018;50(2):e440-
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson’s disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.
4.The relationship between low survival and acute increase of tumor necrosis factor α expression in the lung in a rat model of asphyxial cardiac arrest.
Yoonsoo PARK ; Hyun Jin TAE ; Jeong Hwi CHO ; In Shik KIM ; Taek Geun OHK ; Chan Woo PARK ; Joong Bum MOON ; Myoung Cheol SHIN ; Tae Kyeong LEE ; Jae Chul LEE ; Joon Ha PARK ; Ji Hyeon AHN ; Seok Hoon KANG ; Moo Ho WON ; Jun Hwi CHO
Anatomy & Cell Biology 2018;51(2):128-135
Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.
Animals
;
Blotting, Western
;
Brain
;
Eosine Yellowish-(YS)
;
Heart
;
Heart Arrest*
;
Hematoxylin
;
Humans
;
Immunohistochemistry
;
Inflammation
;
Lung*
;
Models, Animal*
;
Mortality
;
Rats*
;
Survival Rate
;
Tumor Necrosis Factor-alpha*
5.Effects of Oncostatin M on Invasion of Primary Trophoblasts under Normoxia and Hypoxia Conditions.
Jeong ha WIE ; Hyun Sun KO ; Sae Kyung CHOI ; In Yang PARK ; Ahyoung KIM ; Ho Shik KIM ; Jong Chul SHIN
Yonsei Medical Journal 2018;59(7):879-886
PURPOSE: To investigate the effect of oncostatin M (OSM) on protein expression levels and enzymatic activities of matrix metalloprotainase (MMP)-2 and MMP-9 in primary trophoblasts and the invasiveness thereof under normoxia and hypoxia conditions. MATERIALS AND METHODS: Protein expression levels and enzymatic activities of MMP-2 and MMP-9 in primary trophoblasts under normoxia and hypoxia conditions were examined by Western blot and zymography, respectively. Effects of exogenous OSM on the in vitro invasion activity of trophoblasts according to oxygen concentration were also determined. Signal transducer and activator of transcription 3 (STAT3) siRNA was used to determine whether STAT3 activation in primary trophoblasts was involved in the effect of OSM. RESULTS: OSM enhanced protein expression levels and enzymatic activities of MMP-2 and MMP-9 in term trophoblasts under hypoxia condition, compared to normoxia control (p < 0.05). OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly suppressed by STAT3 siRNA silencing under normoxia and hypoxia conditions (p < 0.05). Hypoxia alone or OSM alone did not significantly increase the invasiveness of term trophoblasts. However, the invasion activity of term trophoblasts was significantly increased by OSM under hypoxia, compared to that without OSM treatment under normoxia. CONCLUSION: OSM might be involved in the invasiveness of extravillous trophoblasts under hypoxia conditions via increasing MMP-2 and MMP-9 enzymatic activities through STAT3 signaling. Increased MMP-9 activity by OSM seems to be more important in primary trophoblasts.
Anoxia*
;
Blotting, Western
;
In Vitro Techniques
;
Oncostatin M*
;
Oxygen
;
RNA, Small Interfering
;
STAT3 Transcription Factor
;
Trophoblasts*
6.First Blindness Cases of Horses Infected with Setaria Digitata (Nematoda: Filarioidea) in the Republic of Korea.
Jihun SHIN ; Kyu Sung AHN ; Guk Hyun SUH ; Ha Jung KIM ; Hak Sub JEONG ; Byung Su KIM ; Eunsang CHOI ; Sung Shik SHIN
The Korean Journal of Parasitology 2017;55(6):667-671
Ocular setariases of cattle were reported but those of equine hosts have never been reported in the Republic of Korea (Korea). We found motile worms in the aqueous humor of 15 horses (Equus spp.) from 12 localities in southern parts of Korea between January 2004 and November 2017. After the affected animals were properly restrained under sedation and local anesthesia, 10 ml disposable syringe with a 16-gauge needle was inserted into the anterior chamber of the affected eye to successfully remove the parasites. The male worm that was found in 7 of the cases showed a pair of lateral appendages near the posterior terminal end of the body. The papillar arrangement was 3 pairs of precloacal, a pair of adcloacal, and 3 pairs of postcloacal papillae, plus a central papilla just in front of the cloaca. The female worms found in the eyes of 8 horses were characterized by the tapering posterior terminal end of the body with a smooth knob. Worms were all identified as Setaria digitata (von Linstow, 1906) by the morphologic characteristics using light and electron microscopic observations. This is the first blindness cases of 15 horses infected with S. digitata (Nematoda: Filarioidea) in Korea.
Anesthesia, Local
;
Animals
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Anterior Chamber
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Aqueous Humor
;
Blindness*
;
Cattle
;
Cloaca
;
Female
;
Horses*
;
Humans
;
Korea
;
Male
;
Needles
;
Parasites
;
Republic of Korea*
;
Setariasis
;
Syringes
7.Molecular Prevalence of Acarapis Mite Infestations in Honey Bees in Korea.
Ah Jin AHN ; Kyu Sung AHN ; Jin Hyeong NOH ; Young Ha KIM ; Mi Sun YOO ; Seung Won KANG ; Do Hyeon YU ; Sung Shik SHIN
The Korean Journal of Parasitology 2015;53(3):315-320
Acarapis mites, including Acarapis woodi, Acarapis externus, and Acarapis dorsalis, are parasites of bees which can cause severe damage to the bee industry by destroying colonies and decreasing honey production. All 3 species are prevalent throughout many countries including UK, USA, Iran, Turkey, China, and Japan. Based on previous reports of Acarapis mites occurring in northeast Asia, including China and Japan, we investigated a survey of Acarapis mite infestations in honey bees in Korean apiaries. A total of 99 colonies of Apis mellifera were sampled from 5 provinces. The head and thorax of 20 bees from each colony were removed for DNA extraction. PCR assays were performed with 3 primer sets, including T, A, and K primers. Results indicated that 42.4% (42/99) of samples were Acarapis-positive by PCR assay which were sequenced to identify species. Each sequence showed 92.6-99.3% homology with reference sequences. Based on the homology, the number of colonies infected with A. dorsalis was 32 which showed the highest infection rate among the 3 species, while the number of colonies infected with A. externus and A. woodi was 9 and 1, respectively. However, none of the Acarapis mites were morphologically detected. This result could be explained that all apiaries in the survey used acaricides against bee mites such as Varroa destructor and Tropilaelaps clareae which also affect against Acarapis mites. Based on this study, it is highly probable that Acarapis mites as well as Varroa and Tropilaelaps could be prevalent in Korean apiaries.
Animals
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Bees/*parasitology
;
Mites/classification/*genetics/physiology
;
Molecular Sequence Data
;
Phylogeny
;
Prevalence
;
Republic of Korea
8.Discordance between ambulatory versus clinic blood pressure according to global cardiovascular risk group.
Jinho SHIN ; Sung Ha PARK ; Ju Han KIM ; Sang Hyun IHM ; Kwang Il KIM ; Woo Shik KIM ; Wook Bum PYUN ; Yu Mi KIM ; Sung Il CHOI ; Soon Kil KIM
The Korean Journal of Internal Medicine 2015;30(5):610-619
BACKGROUND/AIMS: The detection of white coat hypertension (WCH), treated normalized hypertension, and masked hypertension (MH) is important to improve the effectiveness of hypertension management. However, whether global cardiovascular risk (GCR) profile has any effect on the discordance between ambulatory blood pressure (ABP) and clinic blood pressure (CBP) is unknown. METHODS: Data from 1,916 subjects, taken from the Korean Multicenter Registry for ABP monitoring, were grouped according to diagnostic and therapeutic thresholds for CBP and ABP (140/90 and 135/85 mmHg, respectively). GCR was assessed using European Society of Hypertension 2007 guidelines. RESULTS: The mean subject age was 54.1 ± 14.9 years, and 48.9% of patients were female. The discordancy rate between ABP and CBP in the untreated and treated patients was 32.5% and 26.5%, respectively (p = 0.02). The prevalence of WCH or treated normalized hypertension and MH was 14.4% and 16.0%, respectively. Discordance between ABP and CBP was lower in the very high added-risk group compared to the moderate added-risk group (odds ratio [OR], 0.649; 95% confidence interval [CI], 0.487 to 0.863; p = 0.003). The prevalence of WCH or treated normalized hypertension was also lower in the very high added-risk group (OR, 0.451; 95% CI, 0.311 to 0.655). CONCLUSIONS: Discordance between ABP and CBP was observed more frequently in untreated subjects than in treated subjects, and less frequently in the very high added-risk group, which was due mainly to the lower prevalence of WCH or treated normalized hypertension.
Adult
;
Aged
;
*Blood Pressure
;
*Blood Pressure Monitoring, Ambulatory
;
Chi-Square Distribution
;
Cross-Sectional Studies
;
Female
;
Humans
;
Logistic Models
;
Male
;
Masked Hypertension/*diagnosis/epidemiology/physiopathology
;
Middle Aged
;
Multivariate Analysis
;
Observer Variation
;
Odds Ratio
;
*Office Visits
;
Predictive Value of Tests
;
Prevalence
;
Registries
;
Reproducibility of Results
;
Republic of Korea/epidemiology
;
Risk Assessment
;
Risk Factors
;
White Coat Hypertension/*diagnosis/epidemiology/physiopathology
9.Efficacy of silver ions against Sacbrood virus infection in the Eastern honey bee Apis cerana.
Ah Jin AHN ; Kyu Sung AHN ; Guk Hyun SUH ; Jin Hyeong NOH ; Young Ha KIM ; Mi Sun YOO ; Seung Won KANG ; Sung Shik SHIN
Journal of Veterinary Science 2015;16(3):289-295
Although silver is known to be a broad-spectrum biocidal agent, the effects of this metal against Sacbrood virus have not yet been investigated. In this study, we evaluated the efficacy of silver ions against natural Korean sacbrood virus (KSBV) infection of Apis (A.) cerana. Ten KSBV-infected colonies containing A. cerana with similar strength and activity were selected from an apiary located in Bosung-gun (Korea). Among these, five colonies were randomly assigned to the treatment group that was fed sugar syrup containing 0.2 mg/L silver ions. The other colonies were assigned to the untreated control group in which bees were given syrup without the silver ions. To assess the efficacy of the silver ions, colony strength, colony activity, and the number of dead larvae per hive were measured. During the experimental period, the test group maintained its strength and activity until day 32 while those of bees in the control group decreased sharply after day 8 to 16. Survival duration of the test group was significantly longer (40 days) than that of the control group (21 days). These results strongly indicated that silver ions are effective against KSBV infection in A. cerana.
Animals
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Antiviral Agents/*pharmacology
;
Beekeeping
;
Bees/*virology
;
Ions/pharmacology
;
RNA Viruses/*drug effects
;
Republic of Korea
;
Silver/*pharmacology
10.An Autochthonous Case of Canine Visceral Leishmaniasis in Korea.
Dong Ha BHANG ; Ul Soo CHOI ; Hyun Jeong KIM ; Kyoung Oh CHO ; Sung Shik SHIN ; Hee Jeong YOUN ; Cheol Yong HWANG ; Hwa Young YOUN
The Korean Journal of Parasitology 2013;51(5):545-549
A 12-year-old spayed female mixed-bred dog presented with nasal bleeding of 2 days duration and a skin nodule in the left flank. No abnormalities were found in coagulation profiles and blood pressure. Cytological evaluation of the nodule revealed numerous characteristic round organisms having a nucleus and a bar within macrophages and in the background, consistent with leishmaniasis. In vitro culture was unsuccessful but PCR of the nodular aspirate identified the organisms as Leishmania infantum, and the final diagnosis was canine leishmaniasis. No history of travel to endemic countries was noted. Because the dog had received a blood transfusion 2 years before the illness, serological screening tests were performed in all donor dogs of the commercial blood bank using the commercial Leishmania ELISA test kit, and there were no positive results. Additional 113 dogs with hyperglobulinemia from Seoul were also screened with the same kits but no positive results were obtained. To the best of the author's knowledge this is the first autochthonous case of canine leishmaniasis in Korea.
Animals
;
Base Sequence
;
DNA, Protozoan/chemistry/genetics
;
DNA, Ribosomal/chemistry/genetics
;
Dog Diseases/*diagnosis/epidemiology
;
Dogs
;
Enzyme-Linked Immunosorbent Assay/veterinary
;
Female
;
Giant Cells/pathology
;
Leishmania infantum/genetics/immunology/*isolation & purification
;
Leishmaniasis, Visceral/diagnosis/*veterinary
;
Molecular Sequence Data
;
Polymerase Chain Reaction/veterinary
;
Protozoan Proteins/genetics
;
Republic of Korea
;
Sequence Analysis, DNA/veterinary
;
Serologic Tests/veterinary

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