Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to ...date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ABSTRACT
Aim
Although a National Health Screening Program (NHSP) for chronic kidney disease (CKD) has been implemented in Korea since 2002, its cost‐effectiveness has never been determined. This ...study aimed to estimate the cost‐utility of NHSP for CKD in Korea.
Methods
A Markov decision analytic model was constructed to compare CKD screening strategies of the NHSP with no screening. We developed a model that simulated disease progression in a cohort aged 20–120 years or death from the societal perspective.
Results
Biannual screening starting at age 40 for CKD by proteinuria (dipstick) and estimated glomerular filtration ratio had an ICUR of $66 874/QALY relative to no screening. The targeted screening strategy had an ICUR of $37 812/QALY and $40 787/QALY for persons with diabetes and hypertension, respectively. ICURs improved with lower cost strategies. The most influential parameter that might make screening more cost‐effective was the effectiveness of treatment on CKD to decrease disease progression and mortality.
Conclusions
The Korean NHSP for CKD is more cost‐effective for patients with diabetes or hypertension than the general population, consistent with prior studies. Although it is too early to conclude the cost‐effectiveness of the Korean NHSP for CKD, this study provides evidence that is useful in evaluating the cost‐effectiveness of CKD interventions.
Summary at a Glance
The authors successfully demonstrate that the Korean National Health Screening Program (NHSP) for CKD is more cost‐effective for patients with diabetes or hypertension than the general population.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Equine parvovirus‐hepatitis (EqPV‐H) and equine hepacivirus (EqHV) are etiologically associated with Theiler's disease (TD), causing fulminant equine hepatitis, but the transmission route and ...co‐infection effect remain unclear. We determined EqPV‐H and EqHV prevalence and coinfection rate in 160 serum and 114 faecal samples using nested polymerase chain reaction. Amino acid and nucleotide analyses were performed and phylogenetic trees were constructed. By measuring liver‐specific parameters (AST, GGT, TBIL and A/G ratio), hepatopathological changes in viremia status were compared. We found a high prevalence (EqPV‐H: 10.6% in serum, 5.3% in faeces; EqHV: 8.1% in serum) and coinfection rate (35.3% in EqPV‐H) of TD‐causing agents. The newly identified EqPV‐H genomes showed high nucleotide and amino acid similarities with previously reported strains in the USA, China and Austria. In phylogenetic tree and recombination analysis, a natural recombination event was confirmed between Chinese and Korean strains. In the EqPV‐H or EqHV viremic horses, AST was significantly elevated and at least two liver‐specific parameters were outside the reference intervals in 43.5% (10/23) of horses. To our knowledge, this is the first prevalence field study of EqPV‐H and EqHV using both serum and faeces, providing further evidence of faecal‐oral transmission of TD. These epidemiologic and clinicopathologic analyses specify the risk factors of TD infection and promote disease prevention strategy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Hemophilia is a hereditary disease that remains incurable. Although innovative treatments such as gene therapy or bispecific antibody therapy have been introduced, substantial unmet needs still exist ...with respect to achieving long-lasting therapeutic effects and treatment options for inhibitor patients. Antithrombin (AT), an endogenous negative regulator of thrombin generation, is a potent genome editing target for sustainable treatment of patients with hemophilia A and B. In this study, we developed and optimized lipid nanoparticles (LNPs) to deliver Cas9 mRNA along with single guide RNA that targeted AT in the mouse liver. The LNP-mediated CRISPR-Cas9 delivery resulted in the inhibition of AT that led to improvement in thrombin generation. Bleeding-associated phenotypes were recovered in both hemophilia A and B mice. No active off-targets, liver-induced toxicity, and substantial anti-Cas9 immune responses were detected, indicating that the LNP-mediated CRISPR-Cas9 delivery was a safe and efficient approach for hemophilia therapy.
Equine parvovirus‐hepatitis (EqPV‐H) is one of the etiological agents of Theiler's disease, causing fulminant hepatitis; however, its transmission route and pathogenesis remain unclear. In the ...present study, we aimed to determine EqPV‐H shedding in oral/nasal/vaginal swabs or semen samples from horses living in Korea using nested polymerase chain reaction. We then used the data obtained to investigate various risk factors associated with EqPV‐H including viral shedding, hepatopathological changes, and genetic diversity. Our data revealed occurrence of EqPV‐H shedding in these animals (oral: 3/102 2.9%; nasal: 3/102 2.9%; semen: 1/9 11.1%) and identified that both age and country of foaling were significantly associated with EqPV‐H shedding (p < .05). In addition, we noted that one of the newly isolated strains clustered separately from the other strains in the phylogenetic tree, revealing unique nucleotide and amino acid substitutions. This is a field surveillance study providing evidence of natural and venereal shedding of EqPV‐H and describing its presence in both oral/nasal fluids and semen. This epidemiological and clinical analysis may help specify the clinicopathological features of EqPV‐H and facilitate the development of novel disease prevention strategies.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine ...transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2–infected dogs, particularly involving blood–brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2–associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sarcopenia is an important factor of functional impairment related to aging. This study is conducted to investigate the prevalence of sarcopenia and sarcopenic obesity in Korean population.
...Representative Korean men (4,486) and women (5,999) aged 20 years or older were analyzed from the Fourth Korean National Health and Nutritional Examination Surveys. Sarcopenia was classified into Class I defined relative skeletal muscle mass loss within 1-2 SD of the gender-specific mean for healthy young adults and Class II below 2 SD. Relative skeletal muscle mass was represented by the appendicular skeletal muscle mass adjusted by height and body weight. Sarcopenic obesity was considered present in Class II sarcopenic participants whose waist circumference was more than or equal to 90 cm for men and more than or equal to 85 cm for women, respectively.
The prevalence of Class II sarcopenia in the Korean elderly population was 12.4% for men and 0.1% for women by height-adjusted definition and 9.7% for men and 11.8% for women by weight-adjusted definition. The prevalence of sarcopenic obesity was 7.6% for men and 9.1% for women by weight-adjusted definition but nearly zero for men and women by height-adjusted definition. The prevalence of sarcopenia increased with age for men but for women only when applied with weight-adjusted definition.
The prevalence of sarcopenia and sarcopenic obesity differs by gender and definition criteria. The height-adjusted definition may tend to underestimate the prevalence of sarcopenia and sarcopenic obesity, especially in women.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 269 million people and killed more than 5.3 million people worldwide. Although fomite transmission of SARS-CoV-2 ...has been continuously reported, few studies have been conducted on food contact surfaces. Therefore, this study aimed to investigate the viability of coronaviruses on food contact surfaces and to remove SARS-CoV-2 contaminated on food contact surfaces with disinfectants. At 20 °C, SARS-CoV-2 was inactivated within 48 h on all food contact surfaces. At 4 °C, it was inactivated at 48 h on kraft paper and 96 h on parchment paper, but it was viable up to 5 days in low-density polyethylene (LDPE). At −20 °C, SARS-CoV-2 did not decrease by even 1 log on all food contact surfaces until 5 days. Treatment with 70% ethanol or 1000 ppm sodium hypochlorite for 5 min was sufficient to completely remove SARS-CoV-2 from 6 food contact surfaces. Similarly, UV-C irradiation at 60 mJ/cm2 eliminated SARS-CoV-2 contaminated on food contact surfaces. Also, the wiping test showed that even wiping an area contaminated with SARS-CoV-2 with a cloth moistened with 70% ethanol or 1000 ppm sodium hypochlorite, it took 5 min to inactivate the virus. Our findings suggested that SARS-CoV-2 contaminated on food contact surfaces in local retail may be viable enough to be transported home. However, if the type and method of use of the disinfectant suggested in this study are followed, it is possible to sufficiently control the fomite transmission of SARS-CoV-2 through food contact surfaces at home.
•SARS-CoV-2 survived up to 5 d under different temperatures on food packaging surfaces.•SARS-CoV-2 was more susceptible to ethanol than sodium hypochlorite.•Inactivation of SARS-CoV-2 was dependent on sufficient exposure time after wiping with disinfectants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Highlights•A nanogel vaccine encapsulating rabbit HEV capsid protein was developed. •The nanogel vaccine induced anti-HEV antibodies, IL-12, and IFN-γ. •The nanogel vaccine completely protected ...rabbits from HEV infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Equine parvovirus-hepatitis (EqPV-H) is a newly identified etiologic agent of Theiler's disease (TD). We present a case of EqPV-H-related fulminant hepatitis in a 14-year-old thoroughbred mare in ...Korea. The mare had acute hepatopathy and gastrointestinal symptoms, with abnormal liver-related blood parameters. The horse was born in the USA and imported to Korea in 2017, with no history of administration of equine biological products after entry into Korea. The horse was diagnosed with EqPV-H-associated hepatitis after abdominal ultrasonography, laparotomy, and nested polymerase chain reaction (PCR) and in situ hybridization (ISH) assays. The serum, nasal swab, oral swab, and liver biopsy were positive for EqPV-H according to the PCR assay. Genetic analysis of the partial NS1 gene of EqPV-H showed a unique nucleotide substitution, distinct from that in previously deposited strains. EqPV-H DNA was found not only in hepatocytes but also in bile duct epithelium and Kupffer cells, particularly via ISH. To the best of our knowledge, this is the first case of EqPV-H-associated TD in Asia, providing the first clinical evidence for viral shedding from the mouth and nose, and identification of EqPV-H in the liver. This study contributes to a better understanding of the pathological features of EqPV-H-associated TD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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