Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for Diagnosis of Invasive Aspergillosis in Patients With Hematologic Malignancy or COVID-19.

BACKGROUND: We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). METHODS: Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. RESULTS: Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. CONCLUSIONS: Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

Frequency and Risk Factor Analysis for Metronidazole-Associated Neurologic Adverse Events.

BACKGROUND: Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events. OBJECTIVE: To investigate the risk factors and frequency of metronidazole-associated neurological adverse events. DESIGN: This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022. PARTICIPANTS: In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole. MAIN MEASURES: Frequency and risk factors for metronidazole-associated neurological adverse events. KEY RESULTS: Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events. CONCLUSIONS: The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events.

Prevalence, clinical significance, and persistence of autoantibodies in COVID-19.

BACKGROUND: Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. METHODS: We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. RESULTS: A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-ß2Glycoprotein1 antibody (aß2-GPI) in 32 patients, and IgG aß2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aß2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. CONCLUSION: A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

Risk factors of pneumothorax and pneumomediastinum in COVID-19: a matched case-control study.

BACKGROUND: During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case-control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. METHODS: This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1-2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. RESULTS: 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72-0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041). CONCLUSIONS: Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Relationship between freshwater harmful algal blooms and neurodegenerative disease incidence rates in South Korea.

BACKGROUND: Due to anthropogenic activities and global warming, the severity and distribution of harmful algal blooms (HABs) have been increasing steadily worldwide, including in South Korea (S. Korea). Previous studies reported that exposure to HABs could increase the risk of HAB-related diseases. However, very few studies examined the linkage between HABs and disease occurrence, particularly in S. Korea. The objective of this study was to evaluate the potential impact of HABs on neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, and motor neuron disease, at a population level. METHODS: Thirteen-year data (2005-2017) for chlorophyll-a (chl-a) concentrations as a bloom-related parameter, annual numbers of NDs, and population information were collected. First, the entire area of S. Korea was divided into a grid of 1 km, and the population number in each 1-km grid was collected using the Statistical Geographic Information Service Plus system. Cross-sectional time series data were analyzed with two statistical models, a generalized linear mixed model and a generalized linear model. RESULTS: The results show a general trend of increasing chl-a concentration and NDs year by year. We observed positive correlations between HAB intensity and the incidence rate of NDs. Particularly, HABs seem to have the most long-term carry-over effect on Parkinson's disease. Another key finding was that a 5-km radius from the HAB location was the boundary that showed the most significant associations with three NDs. CONCLUSIONS: This study provides statistical evidence that supports the potential risk of NDs from the exposure to HAB. Thus, it is recommended to monitor a broad spectrum of cyanotoxins, including neurotoxins, in bloom-affected regions in S. Korea and epidemiological studies in the future.

Colonization of toxic cyanobacteria on the surface and inside of leafy green: A hidden source of cyanotoxin production and exposure.

Cyanobacteria are a threat to the safety of water sources for drinking, recreation, and food production, because some cyanobacteria, such as Microcystis, produce cyanotoxins. However, the colonization of plants by Microcystis and the fate of their toxin, microcystins (MCs), in agricultural environments have not been thoroughly studied. This study examined the colonization of lettuce, as a representative of leafy greens, by Microcystis and its potential impact on food safety and crop health. The surfaces of lettuce leaves were exposed to environmentally relevant concentrations of M. aeruginosa (104, 106, and 108mcyE gene copies/mL) by mimicking contamination scenarios during cultivation, such as spraying irrigation with contaminated water or deposits of airborne Microcystis. Scanning electron microscope (SEM) and droplet digital PCR were used. The results showed that M. aeruginosa colonized the surface of leaves and MCs accumulated in the edible part of the lettuce (>20 µg/kg of lettuce). Crop productivity (length, weight, and number of leaves) was negatively affected. The SEM images provide evidence that M. aeruginosa deposited on the lettuce surface can be internalized via natural opening sites of the leaves and then proliferate within the plants. Our findings imply that toxic cyanobacteria contamination in agricultural environments can be a significant cyanotoxin exposure pathway.

Anti-Inflammatory and Anti-Diabetic Effect of Black Soybean Anthocyanins: Data from a Dual Cooperative Cellular System.

Obesity is characterized by elevated infiltration of macrophages into adipose tissue, leading to the development of insulin resistance. The black soybean seed coat is a rich source of anthocyanins with antioxidative and anti-inflammatory activities. This study investigated the effects of black soybean anthocyanin extract (BSAn) on obesity-induced oxidative stress, the inflammatory response, and insulin resistance in a coculture system of hypertrophied 3T3-L1 adipocytes and RAW264 macrophages. Coculture of adipocytes with macrophages increased the production of reactive oxygen species and inflammatory mediators and cytokines (NO, MCP-1, PGE2, TNFα, and IL-6) and the release of free fatty acids but reduced anti-inflammatory adiponectin secretion. BSAn treatment (12.5, 25, 50, and 100 µg/mL) alleviated the coculture-induced changes (p < 0.001) and inhibited coculture-induced activation of JNK and ERK signaling (p < 0.01). BSAn also blocked the migration of RAW264.7 macrophages toward 3T3-L1 adipocytes. In addition, treatment with BSAn increased PPARγ expression and glucose uptake in response to insulin in hypertrophied 3T3-L1 adipocyte and RAW264.7 macrophage coculture (p < 0.01). These results demonstrate that BSAn attenuates inflammatory responses and improves adipocyte metabolic function in the coculture of hypertrophied 3T3-L1 adipocytes and RAW264.7 macrophages, suggesting the effectiveness of BSAn for obesity-induced insulin resistance.

Harmful algal blooms and liver diseases: focusing on the areas near the four major rivers in South Korea.

Freshwater harmful algal blooms (HABs) have become a global concern because blooms contain cyanotoxins that can cause liver damage and other negative health impacts. In South Korea, HABs have been frequently observed along the major rivers (Han, Geum, Nakdong, and Youngsan) in recent years. However, there are hardly any studies that report a linkage between HABs and human health, especially along the four major rivers where dams, weirs, and reservoirs were constructed, and sediments were dredged under the Four Major Rivers Project (FMRP) that ended in 2012. The goals of this study were to summarize spatial distribution patterns of HABs and investigate a potential association between HABs and liver diseases. Chlorophyll-a concentration was used to estimate bloom intensity since it was the only available bloom-related parameter that covers the entire rivers. Liver disease data (ICD-10 codes: K71-K77) were sorted by administrative districts. Generalized linear mixed model was used to analyze the bloom, liver diseases, and population data (2005-2016). The results show that chlorophyll-a levels significantly increased since 2013, except Han River region. There was a significant association between HAB intensity and incidence rate of liver diseases, except Han River area, and the extent of association significantly increased after the completion of the FMRP. For future studies, more in-depth epidemiological investigations are warranted in those areas to accurately determine more specific associations between HABs and liver diseases as well as other bloom-related diseases and symptoms. In addition, identification of major exposure pathways to cyanotoxins is needed to better protect public health in those bloom-affected areas.

Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.

Genome-wide DNA Methylation Profiles of Small Intestine and Liver in Fast-growing and Slow-growing Weaning Piglets.

Although growth rate is one of the main economic traits of concern in pig production, there is limited knowledge on its epigenetic regulation, such as DNA methylation. In this study, we conducted methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) to compare genome-wide DNA methylation profile of small intestine and liver tissue between fast- and slow-growing weaning piglets. The genome-wide methylation pattern between the two different growing groups showed similar proportion of CpG (regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence) coverage, genomic regions, and gene regions. Differentially methylated regions and genes were also identified for downstream analysis. In canonical pathway analysis using differentially methylated genes, pathways (triacylglycerol pathway, some cell cycle related pathways, and insulin receptor signaling pathway) expected to be related to growth rate were enriched in the two organ tissues. Differentially methylated genes were also organized in gene networks related to the cellular development, growth, and carbohydrate metabolism. Even though further study is required, the result of this study may contribute to the understanding of epigenetic regulation in pig growth.

Clinical and microbiological characteristics of female patients with acute pyelonephritis who experienced urinary tract infections within the previous year.

BACKGROUND: This study aimed to examine the clinical and microbiological characteristics of female patients with recurrent acute pyelonephritis (APN). METHODS: A retrospective cohort study was conducted at a tertiary care hospital in South Korea from July 2019 to December 2021. All female patients aged ≥ 19 years who were diagnosed with community-acquired APN on admission were enrolled. The recurrent group included patients with APN who experienced urinary tract infections within the previous year. The clinical characteristics, types of causative organisms, major antibiotic resistance, and molecular characteristics of Escherichia coli strains were compared between the recurrent and non-recurrent groups. RESULTS: A total of 285 patients with APN were analyzed, including 41 (14.4%) in the recurrent group. Compared to the non-recurrent group, the recurrent group had a higher Charlson Comorbidity Index (1.8 ± 2.1 vs. 1.1 ± 1.5; P = 0.01) and a higher proportion of bladder abnormalities, such as neurogenic bladder (12.2% vs. 2.0%; P = 0.001) and urinary catheterization (12.2% vs. 1.6%; P < 0.001). Escherichia coli was the most common causative organism in both groups. The proportion of Klebsiella pneumoniae (17.1% vs. 4.7%; P = 0.007) and Pseudomonas aeruginosa (5.7% vs. 0.5%; P = 0.014) as a causative organism was higher in the recurrent group. Regarding the microbiological characteristics of Escherichia coli, there were no significant differences in the proportion of antibiotic resistance, phylogenetic groups, resistance genes, and virulence factors between the two groups. Multivariable analysis showed that neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were significantly associated with recurrent APN. CONCLUSIONS: The proportion of causative organisms except Escherichia coli was higher in the recurrent group than in the non-recurrent group. Neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were risk factors for recurrent APN.

Pentraxin 3 as an Immune Recovery Marker in HIV Infection After Combination Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection causes chronic inflammation in affected individuals. Chronic inflammation may hinder immunological recovery. Treatment with combination antiretroviral therapy (cART) is insufficient to reduce inflammation. Pentraxin 3 (PTX3) is an inflammatory marker associated with cardiovascular disease, malignancy, and acute infection. This study evaluated the usefulness of serum PTX3 levels in measuring inflammation levels, which may be associated with the probability of immune recovery in people living with HIV (PLH). In this single-center prospective study, we measured serum PTX3 levels in PLH treated with cART. Clinical information on HIV status, type of cART administered, and CD4+ and CD8+ T cell counts at the initial diagnosis of HIV and at study enrollment was obtained from each participant. PLH were divided into good and poor responder groups according to their CD4+ T cell counts at enrollment. A total of 198 PLH were enrolled in this study. A total of 175 and 23 participants were assigned to the good and poor responder groups, respectively. The poor responder group exhibited higher PTX3 levels (0.53 ng/mL vs. 1.26 ng/mL, p = .032). Logistic regression analysis demonstrated that low body mass index [odds ratio (OR) = 0.8, p = .010], low initial CD4+ T cell counts at diagnosis (OR = 0.994, p = .001), and high PTX3 levels (OR = 1.545, p = .006) are clinical factors that were significantly associated with poor immune recovery in PLH. According to the Youden index, PTX3 levels >1.25 ng/mL are associated with poor immune recovery. PLH should be clinically, virologically, and immunologically evaluated. Serum PTX level is a useful inflammatory marker associated with immune recovery in PLH treated with cART.

Carbapenem-resistant Acinetobacter baumannii Outbreak in a COVID-19 Isolation Ward and Successful Outbreak Control with Infection Control Measures.

BACKGROUND: Even amid the coronavirus disease-19 (COVID-19) pandemic, the spread of multidrug-resistant bacteria and infection control are still important tasks. After recognizing the carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak that occurred in the isolation room for COVID-19, we would like to introduce what infection control measures were implemented to eradicate it. MATERIALS AND METHODS: All COVID-19 patients with CRAB in any specimen admitted to the COVID-19 isolation ward of the tertiary hospital in Korea from October to November 2021 were analyzed. RESULTS: During the outbreak, 23 patients with COVID-19 and CRAB infections were identified. The index case was an 85-year-old female referred from a long-term care facility. CRAB was identified in sputum culture in most patients (91.3%). The CRAB outbreak occurred mainly in the rooms around the index case. Environmental cultures on the floor, air inlet, air outlet, and window frame of the rooms were performed. The antimicrobial resistance patterns of CRAB from patients and the environment were identical; whole-genome sequencing analyses revealed isolated clonality. Infection control measures with enhanced environmental cleaning using 1,000 ppm sodium hypochlorite and phenolic compounds, enhanced hand hygiene, additional education, and mandatory additional gowning and gloving of COVID-19 personal protective equipment (PPE) were applied on 29 October. No CRAB infection cases occurred from 2 November for two weeks. CONCLUSION: In addition to applying PPE and COVID-19 precautions in COVID-19 isolation wards, adhering to strict contact precautions along with environmental control can help prevent the spread of multidrug-resistant bacteria.

Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants.

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.

A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19).

Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies' efficacy and long-term viability. Studies reported several antibodies, that received authorization for COVID-19 treatment, are not effective against new variants or subvariants of SARS-CoV-2, hence their distribution has to be paused. Here, the authors reviewed the status of the currently available monoclonal antibodies for COVID-19 treatment, their potential as a therapeutic agent, and the challenges ahead. To address these issues, the authors presented general information on SARS-CoV-2 and how monoclonal antibodies work against SARS-CoV-2. The authors then focus on the antibodies that have been deployed for COVID-19 treatment and their current status, as well as the evidence supporting their potential as an early intervention against COVID-19. Lastly, the authors discussed some leading obstacles that hinder the development and administration of monoclonal antibodies for the treatment of COVID-19.

Internalization of Salmonella in Leafy Vegetables during Postharvest Conditions.

The consumption of fresh produce is increasing due to its role in promoting a healthy and balanced diet. However, this trend is accompanied by increased foodborne disease cases associated with pathogens such as Escherichia, Listeria, and Salmonella. Previous studies provided evidence that the internalization of foodborne pathogens in fresh produce may be a potential contamination route and may pose a public health risk. This study investigates the combination effects of storage temperature and humidity on Salmonella internalization in six types of leafy greens (iceberg lettuce, romaine lettuce, red lettuce, green onion, spinach, and kale) during the storage stage. The results indicated that temperature plays a critical role in Salmonella internalization, with higher concentrations observed in samples stored at 25 °C compared to those stored at 7 °C. The mean concentration of internalized Salmonella in the iceberg lettuce sample was the highest and that in the green onion sample was the lowest (iceberg lettuce > red lettuce > romaine lettuce > spinach > kale > green onion). Mist conditions also had an impact on internalization. The group treated with mist showed an increase in Salmonella internalization of about 10-30% rather than the group without mist treatment. This research emphasizes the importance of understanding the factors influencing bacterial internalization in fresh produce and highlights the need for proper storage conditions to minimize the risk of contamination and ensure food safety.

Microbial communities in aerosol generated from cyanobacterial bloom-affected freshwater bodies: an exploratory study in Nakdong River, South Korea.

Toxic blooms of cyanobacteria, which can produce cyanotoxins, are prevalent in freshwater, especially in South Korea. Exposure to cyanotoxins via ingestion, inhalation, and dermal contact may cause severe diseases. Particularly, toxic cyanobacteria and their cyanotoxins can be aerosolized by a bubble-bursting process associated with a wind-driven wave mechanism. A fundamental question remains regarding the aerosolization of toxic cyanobacteria and cyanotoxins emitted from freshwater bodies during bloom seasons. To evaluate the potential health risk of the aerosolization of toxic cyanobacteria and cyanotoxins, the objectives of this study were as follows: 1) to quantify levels of microcystin in the water and air samples, and 2) to monitor microbial communities, including toxic cyanobacteria in the water and air samples. Water samples were collected from five sites in the Nakdong River, South Korea, from August to September 2022. Air samples were collected using an air pump with a mixed cellulose ester membrane filter. Concentrations of total microcystins were measured using enzyme-linked immunosorbent assay. Shotgun metagenomic sequencing was used to investigate microbial communities, including toxic cyanobacteria. Mean concentrations of microcystins were 960 µg/L ranging from 0.73 to 5,337 µg/L in the water samples and 2.48 ng/m3 ranging from 0.1 to 6.8 ng/m3 in the air samples. In addition, in both the water and air samples, predominant bacteria were Microcystis (PCC7914), which has a microcystin-producing gene, and Cyanobium. Particularly, abundance of Microcystis (PCC7914) comprised more than 1.5% of all bacteria in the air samples. This study demonstrates microbial communities with genes related with microcystin synthesis, antibiotic resistance gene, and virulence factors in aerosols generated from cyanobacterial bloom-affected freshwater body. In summary, aerosolization of toxic cyanobacteria and cyanotoxins is a critical concern as an emerging exposure route for potential risk to environmental and human health.

Interplays between cyanobacterial blooms and antibiotic resistance genes.

Cyanobacterial harmful algal blooms (cyanoHABs), which are a form of microbial dysbiosis in freshwater environments, are an emerging environmental and public health concern. Additionally, the freshwater environment serves as a reservoir of antibiotic resistance genes (ARGs), which pose a risk of transmission during microbial dysbiosis, such as cyanoHABs. However, the interactions between potential synergistic pollutants, cyanoHABs, and ARGs remain poorly understood. During cyanoHABs, Microcystis and high microcystin levels were dominant in all the nine regions of the river sampled. The resistome, mobilome, and microbiome were interrelated and linked to the physicochemical properties of freshwater. Planktothrix and Pseudanabaena competed with Actinobacteriota and Proteobacteria during cyanoHABs. Forty two ARG carriers were identified, most of which belonged to Actinobacteriota and Proteobacteria. ARG carriers showed a strong correlation with ARGs density, which decreased with the severity of cyanoHAB. Although ARGs decreased due to a reduction of ARG carriers during cyanoHABs, mobile gene elements (MGEs) and virulence factors (VFs) genes increased. We explored the relationship between cyanoHABs and ARGs for potential synergistic interaction. Our findings demonstrated that cyanobacteria compete with freshwater commensal bacteria such as Actinobacteriota and Proteobacteria, which carry ARGs in freshwater, resulting in a reduction of ARGs levels. Moreover, cyanoHABs generate biotic and abiotic stress in the freshwater microbiome, which may lead to an increase in MGEs and VFs. Exploration of the intricate interplays between microbiome, resistome, mobilome, and pathobiome during cyanoHABs not only revealed that the mechanisms underlying the dynamics of microbial dysbiosis but also emphasizes the need to prioritize the prevention of microbial dysbiosis in the risk management of ARGs.

Immunogenicity Differences of the ChAdOx1 nCoV-19 Vaccine According to Pre-Existing Adenovirus Immunity.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6-125.0) vs. 51.0 (17.9-122.3), p = 0.024), 2-3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5-926.5) vs. 555.0 (287.3-926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5-655.3) vs. 176.0 (94.3-255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

Long-term prognosis and overall mortality in patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.