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Purpose@#Necrotizing enterocolitis (NEC) is a devastating disease that can cause mortality in preterm babies. NEC may develop through an apoptotic pathway that is known to be inhibited by vascular endothelial growth factor (VEGF). This study determined whether VEGF exerted a protective effect against the development of NEC and apoptosis in rats. @*Methods@#To determine the effect of VEGF in NEC rats, neonatal rats were randomized into 4 groups: the control group, the NEC group, the NEC + intraperitoneal VEGF (50 ng/kg) group (NEC + VEGF IP group), and the NEC + oral VEGF (50 ng/ kg) group (NEC + VEGF OR group). NEC was induced by lipopolysaccharide/hypoxia and cold stress. The animals were sacrificed 72 hours later. After laparotomy, we obtained a region of the proximal small bowel from the ileocecal valve about 18 cm in length. @*Results@#The NEC histological grade, apoptosis histological score, and caspase-3 activity were lower in the NEC + VEGF IP and OR groups than in the NEC group. In the NEC + VEGF IP and OR groups, the messenger RNA expression of apoptotic and inflammatory genes, such as Bax, NF-κB, p53, Fas, FasL, and PAF-R, but not that of Bcl-2, was decreased, as was the Bax/Bcl-2 protein ratio. Histological analysis revealed that the apoptosis-blocking effect of VEGF was more effective in the NEC + VEGF IP group than in the NEC + VEGF OR group. @*Conclusion@#We identified apoptotic and inflammatory genes to confirm the preventive effect of VEGF pretreatment on NEC in rats. This study presents a novel approach to prevent apoptosis via VEGF pretreatment in rats with lipopolysaccharide/ hypoxia-induced NEC.
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Purpose@#This study examined the incidence and time of onset of retinopathy in premature infants in Korea. @*Methods@#The medical records of premature infants admitted to the neonatal intensive care unit from 2006 to 2018 were reviewed retrospectively. Stages 1 and 2 were classified as mild retinopathy and stages 3 and 4 were considered severe. The incidence, severity, time of diagnosis, associations between retinopathy and birth weight and also gestational age, and clinical characteristics of the treated infants were analyzed. @*Results@#The incidence of retinopathy was 10.9% with an average time of diagnosis at 34.92 weeks postmenstrual age; the frequency of severe retinopathy was 44.97%. Birth weight and gestational age were significantly lower in premature infants with retinopathy than in normal infants. In addition, birth weight was significantly lower in those with severe retinopathy than in those with mild retinopathy. For birth weight and gestational age, the incidence and severity of retinopathy tended to be higher in those with birth weights less than 1,000 g and gestational ages of less than 27 weeks. Of the infants, 4.51% underwent laser photocoagulation; the times of diagnosis, progression to type 1 retinopathy, and treatment were 33.75, 35.06, and 36.04 weeks postmenstrual age, respectively. @*Conclusions@#The incidence and severity of retinopathy of premature infants increased in those with birth weights less than 1,000 g and gestational ages less than 27 weeks. Such infants should be monitored carefully between 32 to 36 weeks of postmenstrual age, when retinopathy is mainly diagnosed.
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Purpose@#To investigate the effects of vascular endothelial growth factor (VEGF) on yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ), a Hippo pathway-related transcription factor, and the role of YAP/TAZ induced by trabecular meshwork stimulation. @*Methods@#Human trabecular meshwork cells were cultured and treated with various VEGF concentrations to verify cell cytotoxicity using the CCK-8 solution. Transforming growth factor β-2 (TGFβ2; 5 ng/mL) and VEGF (30 ng/mL) were applied and YAP/TAZ expression was assessed by western blotting, reverse transcription quantitative polymerase chain reaction and immunocytochemistry. Fibronectin, collagen 1, and myocilin expression were also assessed by western blotting. The cells were stained using Alexa Fluor 488-phalloidin to observe F-actin changes. @*Results@#YAP and TAZ expression increased following TGFβ2 and VEGF treatment for 24 hours. Fibronectin and collagen 1 increased significantly in all three treatment groups, while myocilin increased in the TGFβ2 and TGFβ2+VEGF groups. The F-actin staining showed increased cross-linking in the trabecular meshwork cells. @*Conclusions@#VEGF induced YAP/TAZ signaling and increased trabecular meshwork cell fibrosis. Based on the functional changes caused by VEGF, it is suggested that VEGF and YAP/TAZ may increase aqueous humor outflow resistance in trabecular meshwork cells.
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BACKGROUND/OBJECTIVES@#This study aimed to analyze the potential of school meals in South Korea as a sustainable tool to reduce carbon emissions by focusing on animal- vs.plant-based protein foods.MATERIALS/METHODS: By using a stratified proportional allocation method, 536 out of the 11,082 schools nationwide were selected including 21 kindergartens, 287 elementary-, 120 middle- and 108 high schools. A total of 2,680 meals served for 5 consecutive days (June 21–25, 2021) were collected. We analyzed the average serving amounts of protein foods (animal- vs. plant-based) per meal and then, calculated the estimated average amounts of carbon emission equivalents per meal by applying the conversion coefficients. The t-test and analysis of variance were used for statistical analyses (α = 0.05). @*RESULTS@#The average serving amount of animal-based protein foods per meal was 12.5 g, which was approximately 3 times higher than that of plant-based ones (3.8 g) (P < 0.001); the Meat-group had the highest average amount of 17.0 g, followed by Egg-group (9.6 g), Fishgroup (7.6 g), and Beans-and-Nuts-group (3.8 g) (P < 0.05). Specifically, pork (25.1 g) was ranked first, followed by poultry (19.6 g), processed meat products (18.0 g). The estimated average amount of carbon emission equivalents of animal-based protein foods per meal was 80.1 g CO 2 e, which was approximately 31 times higher than that of plant-based ones (2.6 g CO 2 e) (P < 0.001); the Meat-group had the highest average amount of 120.3 g CO 2 e, followed by Fish-group (44.5 g CO 2 e), Egg-group (25.9 g CO 2 e), and Beans-and-Nuts-group (2.6 g CO 2 e) (P < 0.05). Specifically, processed meat products (270.8 g CO 2 e) were ranked first, followed by pork (91.7 g CO 2 e), and processed fish products (86.6 g CO 2 e). @*CONCLUSIONS@#The results implied that school meals with plant-based alternatives could be a sustainable tool to improve carbon footprint.
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Human microbiome refers to the genetic material of approximately 1013 microorganisms present in the human body. These microbiomes interact significantly with the physiological, metabolic, and immune systems, particularly during pregnancy. Microbiome dysbiosis in pregnant women and their fetuses is associated with obstetric complications and poor neonatal outcomes. Oral and gut microbiomes can influence the placenta, uterus, and fetus via hematogenous translocation. Through ascending translocation, vaginal microbiota can directly affect the uterine environment. Current research focuses on the presence of the placental microbiome, which is characterized by low biomass. However, more well-controlled studies are required to specifically address the contamination issues. Use of antibiotics during pregnancy and the mode of delivery, specifically cesarean section, have been linked to the establishment of the neonatal gut microbiome. Probiotic supplementation may be beneficial during pregnancy, particularly for women receiving antibiotic treatment.
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Background@#Serotonin syndrome is a life-threatening disease if not appropriately treated. This study aimed to investigate the prescription status of contraindicated drug combinations that cause serotonin syndrome and identify the related factors. @*Methods@#A cross-sectional study was conducted using nationwide claims data. Adult patients taking serotonergic drugs with Parkinson’s disease or mental disorders were selected. Based on international medical databases (MDBs) and the Korean Drug Utilization Review (DUR), the status of prescribing contraindicated drug combinations that induce serotonin syndrome, the related factors, and the difference between international MDBs and the Korean DUR were analyzed. @*Results@#Of the 49,773 study subjects, 163 (0.3%) were prescribed contraindicated serotonergic drug combinations based on international MDBs, and among them, only 105 (64.4%) were contraindicated by the Korean DUR. Positive influencing factors for prescribing contraindicated drug combinations include patient age between 65 and 74 and physician’s specialties (neurologists, and orthopedists). Negative influencing factors were physician’s specialty (internists) and medical institution (primary institutions). @*Conclusion@#Despite the implementation of DUR, 3 out of 1,000 study subjects received contraindicated drug combinations that caused serotonin syndrome. Hence, it is necessary to comply with the DUR and improve it in accordance with international MDBs.
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Purpose@#Although there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimal gland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes taking place on the contralateral eye after unilateral LGE to determine whether it is useful as a control. @*Methods@#Seven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGE groups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea, conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive control animals. @*Results@#Compared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctival goblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface became more pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detected in the contralateral LGs of the LGE model. @*Conclusions@#Considering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model may not offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may be regulatory feedback or crosstalk system between both eyes activated in response to LGE.
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Objectives@#. We evaluated changes in income levels in a hearing-impaired population. @*Methods@#. The study subjects were selected from the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 of Koreans ≥40 years old. In total, 5,857 hearing-impaired subjects were matched with 23,428 comparison participants. Differences between the initial income level and income levels at 1, 2, 3, 4, and 5 years post-enrollment were compared between the hearing-impaired and comparison groups. The interaction of time and hearing impairment/comparison was estimated. @*Results@#. Both the hearing-impaired group and the comparison group showed increased income levels over time. In the hearing-impaired group, the income levels at 4 and 5 years post-enrollment were higher than the initial income level (each P<0.001). In the comparison group, the income levels of all the participants after 1–5 years were higher than the initial income level (each P<0.001). The interaction of time and hearing impairment was statistically significant (P=0.021). @*Conclusion@#. The increase in income over time was relatively lower in the hearing-impaired adult population; therefore, the income gap widened between this population and the normal-hearing population.
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Objectives@#. We evaluated changes in income levels in a hearing-impaired population. @*Methods@#. The study subjects were selected from the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 of Koreans ≥40 years old. In total, 5,857 hearing-impaired subjects were matched with 23,428 comparison participants. Differences between the initial income level and income levels at 1, 2, 3, 4, and 5 years post-enrollment were compared between the hearing-impaired and comparison groups. The interaction of time and hearing impairment/comparison was estimated. @*Results@#. Both the hearing-impaired group and the comparison group showed increased income levels over time. In the hearing-impaired group, the income levels at 4 and 5 years post-enrollment were higher than the initial income level (each P<0.001). In the comparison group, the income levels of all the participants after 1–5 years were higher than the initial income level (each P<0.001). The interaction of time and hearing impairment was statistically significant (P=0.021). @*Conclusion@#. The increase in income over time was relatively lower in the hearing-impaired adult population; therefore, the income gap widened between this population and the normal-hearing population.
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Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.
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Background@#Evidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes. @*Methods@#We used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death. @*Results@#Among 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11–23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1–28%; FLI-NAFLD 95% CI, 2–27%; and claims-based NAFLD 95% CI, 2–31%) and a 35–41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8–83%; FLI-NAFLD 95% CI, 5–71%; and claims-based NAFLD 95% CI, 1–92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort. @*Conclusion@#Patients with pre-existing NAFLDs have a higher likelihood of testing SARSCoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic.
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Purpose@#The aim of this study was to examine the validity and reliability of the Korean version of the self-efficacy for managing chronic disease 6-item scale (SECD-6-K). @*Methods@#The English version of the Self-Efficacy for Managing Chronic Disease 6-item Scale first underwent forward and backward translation procedures. The SECD-6-K was then used to collect data from 350 adults diagnosed with chronic diseases. Content, construct, convergent, discriminant, and criterion validity were all evaluated. Reliability was assessed using Cronbach’s α. SPSS 25.0 and the data were analyzed using AMOS 26.0 software. @*Results@#The SECD-6-K consists of six items in two domains: disease management and health behavior. The results for construct, convergent, and discriminant validity were good. Exploratory factor analysis produced eigen values between 2.27 and 3.28, with factors total explained cumulative variance of 91.1%. Confirmatory factor analysis supported goodness of fit and reliability for the modified SECD-6-K model. The criterion validity also showed significant correlation with both the Patient Health Questionnaire and 12-item Short-Form Health Survey version 2. Finally, reliability was found to be excellent. @*Conclusion@#This study identified the high reliability and validity of SECD-6-K. The SECD-6-K is an appropriate tool for determining Korean patients’ self-efficacy in managing their chronic conditions. Therefore, this scale may be used in clinical settings as well as in educational and research settings.
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Purpose@#This study was conducted to investigate the effects of a community-based death education program for older adults. @*Methods@#The study was conducted as a quasi-experimental study with a non-equivalent control group and pretest-posttest design. The subjects were community elders aged over 65 registered at a community health center and were convenience sampled. The experimental group consisted of 33 participants and the control group consisted of 32 participants. Experiments are conducted from June 18 to July 24, 2020. We tested our hypothesis using an independent t-test, and paired t-test. @*Results@#The experimental group had significantly higher scores for psychological well-being than the control group after treatment (t=2.24, p=.028). In general attitude toward the use of life-sustaining technology, however, only the experimental group had a significant difference before and after the experiment with lower scores compared to the control group (t=-5.41, p<.001). @*Conclusion@#We found that the community-based death education program developed in this study was partially effective in improving older adults’ psychological well-being and general attitude toward the use of life-sustaining technology.
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Objective@#External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. @*Methods@#In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. @*Results@#The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. @*Conclusion@#The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer.
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In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro- inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.
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BACKGROUND/OBJECTIVES@#Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages.MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2 ), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. @*RESULTS@#The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2 , which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. @*CONCLUSIONS@#Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.
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BackgroundData on SARS-CoV-2 transmission from a pediatric index patient to others at the school setting are limited. Epidemiologic data on pediatric COVID-19 cases after school opening is warranted. MethodsWe analyzed data of the pediatric patients with COVID-19 collected from the press release of the Korea Centers for Disease Control and Prevention. Information on the school opening delay and re-opening policies were achieved from the press release from Korean Ministry of Education. FindingsThe school openings were delayed three times in March 2020. Online classes started from April 9, and off-line classes started from May 20 to June 8 at four steps in different grades of students. There was no sudden increase in pediatric cases after the school opening, and the proportion of pediatric cases remained around 7.0% to 7.1%. As of July 11, 45 children from 40 schools and kindergartens were diagnosed with COVID-19 after off-line classes started. More than 11,000 students and staff were tested; only one additional student was found to be infected in the same classroom. Among those 45, 32 (71.1%) patients had available information for the source of infection. Twenty-five (25/45, 55.6%) were infected by the family members. The proportions of pediatric patients without information on infection sources were higher in older age group (middle and high school students) than in younger age group (kindergarten and elementary school students) (47.6% vs 12.5%, p=0.010). In the younger age group, 79.1% of children were infected by family members, while only 28.6% of adolescents in the older age group were infected by family members (p<0.001). InterpretationKorea had a successful transition from school closure to re-opening with online and off-line classes. Although partial, off-line school opening did not cause significant school-related outbreak among pediatric population although young children and adolescents may have different epidemiologic features. FundingNone.
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Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 M, 0.12 M, and 26.4 M, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.
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Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.
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Purpose@#This study aimed to determine whether the diagnosis, treatment approach, and prognosis of multiple myeloma (MM) vary according to the presence and type of disability. @*Materials and Methods@#Demographic, socioeconomic, and medical data were obtained from the National Disability Database, the Korean Central Cancer Registry, and the Korean National Health Insurance claims database. An age- and sex-matched cohort was established using a 1:3 ratio constituted with 2,776,450 people with disabilities and 8,329,350 people without disabilities. Adult patients diagnosed with MM were subsequently selected from this cohort. Disabilities were categorized as physical, communication, intellectual or psychological, and affecting the major internal organs. @*Results@#The cohort included 4,090 patients with MM, with a significantly lower rate per 100,000 persons among people with disabilities than among people without disabilities (29.1 vs. 39.4, p < 0.001). People with disabilities were more likely to undergo dialysis treatment at the time of diagnosis (16.3% vs. 10.0%, p < 0.001), but were less likely to undergo autologous stem cell transplantation (37.5% vs. 43.7%, p=0.072). This trend was more evident among patients with intellectual or psychological disabilities. The median overall survival among patients with disabilities was significantly shorter than that among patients without disabilities (36.8 months vs. 51.2 months, p < 0.001). @*Conclusion@#In Korea, people with disabilities generally have a lower rate of MM diagnosis, receive less intensive treatment, and have a lower survival rate than people without disabilities.
