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Background The abuse of nitrous oxide (N 2 O) as a recreational drug has become a growing concern, manifesting in various medical complications. Here, we report the first Korean case of cerebral venous thrombosis (CVT) and pulmonary thromboembolism (PTE) caused by nitrous oxide abuse and anti-phospholipid syndrome. Case presentation A 24-year-old Korean man studying abroad in the USA presented to the emergency department with altered sensorium, gait disturbance, and involuntary leg movements. His history revealed escalating nitrous oxide inhalation from occasional use to daily intake of 100 balloons over six months. The patient’s symptoms were initially attributed to cobalamin deficiency due to N 2 O abuse, leading to hyperhomocysteinemia and subsequent venous thrombosis, particularly CVT and PTE. However, the presence of Lupus Anticoagulant (LA) indicated a potential autoimmune or inflammatory process contributing to thrombotic complications, complicating the diagnosis. The patient’s treatment involved cobalamin supplementation, anticoagulation therapy, and addressing associated substance abuse and depression. Notably, subsequent tests revealed persistent positive LA, highlighting the complexity of the case and the multifactorial nature of N 2 O-induced complications. Conclusions The mechanisms underlying N 2 O-induced thrombotic complications are elucidated, primarily involving the oxidation of cobalamin to its inactive form, leading to hyperhomocysteinemia and endothelial dysfunction. The association with LA suggests a potential autoimmune or inflammatory component, adding another layer of complexity to pathophysiology. This case underscores the importance of recognizing and managing the systemic thrombotic risk associated with N 2 O abuse. It highlights the need for heightened vigilance in diagnosing and managing associated complications, including CVT, and emphasizes the importance of comprehensive diagnostic and treatment approaches addressing both medical and psychiatric aspects. In conclusion, this case serves as a poignant reminder of the serious medical consequences of N 2 O abuse and underscores the importance of early recognition, comprehensive management, and ongoing surveillance to mitigate its adverse effects on individual health and public well-being.

Climate change and nutrient pollution are among the most urgent environmental issues. Enhancing the abundance and/or the activity of beneficial organisms is an attractive strategy to counteract these problems. Dissimilatory nitrate reduction to ammonium (DNRA), which theoretically improves nitrogen retention in soils, has been suggested as a microbial process that may be harnessed, especially since many DNRA-catalyzing organisms have been found to possess nosZ genes and the ability to respire N2O. However, the selective advantage that may favor these nosZ-harboring DNRA-catalyzing organisms is not well understood. Here, the effect of N2O on Nrf-mediated DNRA was examined in a soil isolate, Bacillus sp. DNRA2, possessing both nrfA and nosZ genes. The DNRA metabolism of this bacterium was observed in the presence of C2H2, a NosZ inhibitor, with or without N2O, and the results were compared with C2H2-free controls. Cultures were also exposed to repeated oxic-anoxic transitions in the sustained presence of N2O. The NO2 −-to-NH4 + reduction following oxic-to-anoxic transition was significantly delayed in NosZ-inhibited C2H2-amended cultures, and the inhibition was more pronounced with repeated oxic-anoxic transitions. The possibility of C2H2 involvement was dismissed since the cultures continuously flushed with C2H2/N2 mixed gas after initial oxic incubation did not exhibit a similar delay in DNRA progression as that observed in the culture flushed with N2O-containing gas. The findings suggest a possibility that the oft-observed nosZ presence in DNRA-catalyzing microorganisms secures an early transcription of their DNRA genes by scavenging N2O, thus enhancing their capacity to compete with denitrifiers at oxic-anoxic interfaces. IMPORTANCE Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) is a microbial energy-conserving process that reduces NO3 − and/or NO2 − to NH4 +. Interestingly, DNRA-catalyzing microorganisms possessing nrfA genes are occasionally found harboring nosZ genes encoding nitrous oxide reductases, i.e., the only group of enzymes capable of removing the potent greenhouse gas N2O. Here, through a series of physiological experiments examining DNRA metabolism in one of such microorganisms, Bacillus sp. DNRA2, we have discovered that N2O may delay the transition to DNRA upon an oxic-to-anoxic transition, unless timely removed by the nitrous oxide reductases. These observations suggest a novel explanation as to why some nrfA-possessing microorganisms have retained nosZ genes: to remove N2O that may otherwise interfere with the transition from O2 respiration to DNRA.

Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

Climate change and nutrient pollution are among the most urgent environmental issues. Enhancing the abundance and/or the activity of beneficial organisms is an attractive strategy to counteract these problems. Dissimilatory nitrate reduction to ammonium (DNRA), which theoretically improves nitrogen retention in soils, has been suggested as a microbial process that may be harnessed, especially since many DNRA-catalyzing organisms have been found to possess nosZ genes and the ability to respire N 2 O. However, the selective advantage that may favor these nosZ -harboring DNRA-catalyzing organisms is not well understood. Here, the effect of N 2 O on Nrf-mediated DNRA was examined in a soil isolate, Bacillus sp. DNRA2, possessing both nrfA and nosZ genes. The DNRA metabolism of this bacterium was observed in the presence of C 2 H 2, a NosZ inhibitor, with or without N 2 O, and the results were compared with C 2 H 2 -free controls. Cultures were also exposed to repeated oxic-anoxic transitions in the sustained presence of N 2 O. The NO 2 − -to-NH 4 + reduction following oxic-to-anoxic transition was significantly delayed in NosZ-inhibited C 2 H 2 -amended cultures, and the inhibition was more pronounced with repeated oxic-anoxic transitions. The possibility of C 2 H 2 involvement was dismissed since the cultures continuously flushed with C 2 H 2 /N 2 mixed gas after initial oxic incubation did not exhibit a similar delay in DNRA progression as that observed in the culture flushed with N 2 O-containing gas. The findings suggest a possibility that the oft-observed nosZ presence in DNRA-catalyzing microorganisms secures an early transcription of their DNRA genes by scavenging N 2 O, thus enhancing their capacity to compete with denitrifiers at oxic-anoxic interfaces. Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) is a microbial energy-conserving process that reduces NO 3 − and/or NO 2 − to NH 4 + . Interestingly, DNRA-catalyzing microorganisms possessing nrfA genes are occasionally found harboring nosZ genes encoding nitrous oxide reductases, i.e., the only group of enzymes capable of removing the potent greenhouse gas N 2 O. Here, through a series of physiological experiments examining DNRA metabolism in one of such microorganisms, Bacillus sp. DNRA2, we have discovered that N 2 O may delay the transition to DNRA upon an oxic-to-anoxic transition, unless timely removed by the nitrous oxide reductases. These observations suggest a novel explanation as to why some nrfA -possessing microorganisms have retained nosZ genes: to remove N 2 O that may otherwise interfere with the transition from O 2 respiration to DNRA.

YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.

South Korea is one of the few countries that has succeeded in flattening the curve of new COVID-19 cases and avoiding a second outbreak by implementing multiple strategies, ranging from an individual level to the population level. We aim to discuss the unique strategies and epidemiological characteristics of COVID-19 in South Korea and present a summary of policies implemented by the Korean government during the COVID-19 pandemic. We designed a cross-sectional study of epidemiological data published by the Korea Centers for Disease Control and Prevention on October 1, 2020. We analyzed detailed epidemiological information of COVID-19 cases, including the number of confirmed cases and resulting deaths. As of October 1, 2020, a total of 23,889 confirmed COVID-19 cases and 415 deaths were reported in South Korea. In this paper, we present data on the epidemiological characteristics and transmission of the disease and discuss how the South Korean government, health care providers, and society responded to the COVID-19 outbreak. Understanding the epidemiological characteristics of COVID-19 in South Korea and the government's successful efforts in managing the spread of the disease can provide important insights to other countries dealing with the ongoing pandemic.

Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of , , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.

(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631–2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221–0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670–5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.

Paul's rhetoric in 1 Corinthians has been the focus of scholarly argument, but not much attention is paid to his inconsistent attitude towards rhetoric. Although Paul shows a refined rhetorical skill in his discourse, he is critical of rhetoric when he states that his proclamation of the gospel is not in persuasive words. Such deprecation of rhetoric was not unfamiliar to the people of Paul's time as can be seen in philosophers and orators who responded to public critique of rhetorical manipulation by dissociating themselves from it. And why does Paul deny that he speaks “in persuasive words of wisdom”? The dominant opinion has been that Paul was critical of using rhetoric in Christian proclamation because the Corinthians so much cherished it. But considering the apparent level of education of the Corinthians—“not many of you were wise by human standards” (1 Cor 1:26)—it is unlikely that they were rhetorically skilled. Rather Paul appears to respond to the Corinthians' doubt about his using rhetoric while at the same time persuading them to set aside their spiritual freedom as a sign of factionalism and unite under his authority. This study argues that it was the Corinthians who preferred spiritually inspired speech and thought that eloquent speech did not contain the power of the Spirit. Paul, then, was the person who favored rhetoric and was criticized by them for his rhetorical skill. In the digression of 1 Cor 1:18–2:16 Paul attempts to prove himself agreeable to the Corinthian congregation by denying the persuasive power of rhetoric in his proclamation and claiming to demonstrate the spirit. Yet Paul's emphasis on intelligible speech in 1 Cor 12 and 14 contradicts this apparent preference for spiritual power over eloquent speech in 1:18–2:16. This confirms that Paul's criticism of rhetoric is a rhetorical device necessary to prepare the audience to accept his direction.