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BACKGROUND: Despite the widespread use of attention-deficit hyperactivity disorder (ADHD) medications and their known sympathomimetic effects on the cardiovascular system, cardiovascular risk assessment of these medications using comprehensive global data is limited. This study investigated the association between individual ADHD medications and cardiovascular disease (CVD) using global pharmacovigilance data. METHODS: Reports from the World Health Organization international pharmacovigilance database were utilized (1967-2023; total reports, n=131,255,418). Reporting odds ratios (ROR), and information components (IC) were calculated to evaluate the association between each medication and specific CVDs. RESULTS: We identified 13,344 CVD cases related to ADHD medications out of 146,489 cases of all reports on ADHD medications. Cumulative reports on ADHD medications have shown a steady increase, notably in adults since 2010. ADHD medications were associated with a higher risk of CVD overall (ROR [95 % CI], 1.60 [1.58-1.63]; IC [IC0.25], 0.63 [0.60]), with a higher association observed in females than in males. Among specific CVDs, all drugs were associated with an increased risk of torsade de pointes/QT prolongation, cardiomyopathy, and myocardial infarction. Conversely, heart failure, stroke, and cardiac death/shock were exclusively associated with amphetamines. Lisdexamfetamine showed a weaker association with all CVDs compared to amphetamines, and methylphenidate exhibited the lowest overall association with CVD. Atomoxetine had the second-highest association with torsade de pointes/QT prolongation. CONCLUSIONS: The associations between CVDs and ADHD medications vary, with amphetamines posing a higher risk, while lisdexamfetamine and methylphenidate exhibit better safety profiles.

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BACKGROUND: The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear. METHODS: Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses. RESULTS: Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20-4.99). CONCLUSION: This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.

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INTRODUCTION: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic. METHODS: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007-2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or ß-coefficients for these factors across multiple categories. RESULTS: During the study period (2007-2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3-21.3), while among males, it was 15.6% (13.8-17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5-3.2] in 2007-2009 to 4.7% [3.9-5.4] in 2022; AR: from 11.7% [11.1-12.4] in 2007-2009 to 17.4% [16.0-18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese. CONCLUSIONS: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma.

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We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05-1.08]) and postnatal life (1.05 [1.03-1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09-1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05-1.08]) and severe outcomes (1.17 [1.09-1.26]), especially for intellectual disability (1.12 [1.07-1.17]), ADHD (1.10 [1.07-1.13]), anxiety (1.06 [1.02-1.11]), mood (1.06 [1.00-1.12]), and autism (1.03 [1.01-1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6-12) and 12 % (7-17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription.

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BACKGROUND: Type 2 diabetes poses an increasing disease burden in South Korea. The development and management of type 2 diabetes are closely related to lifestyle and socioeconomic factors, which have undergone substantial changes over the past few decades, including during the COVID-19 pandemic. OBJECTIVE: This study aimed to investigate long-term trends in type 2 diabetes prevalence, awareness, treatment, and control. It also aimed to determine whether there were substantial alterations in the trends during the pandemic and whether these changes were more pronounced within specific demographic groups. METHODS: This study examined the prevalence, awareness, treatment, and control of type 2 diabetes in a representative sample of 139,786 South Koreans aged >30 years, using data from the National Health and Nutrition Examination Survey and covering the period from 1998 to 2022. Weighted linear regression and binary logistic regression were performed to calculate weighted ß coefficients or odds ratios. Stratified analyses were performed based on sex, age, region of residence, obesity status, educational background, household income, and smoking status. ß (difference) was calculated to analyze the trend difference between the prepandemic period and the COVID-19 pandemic. To identify groups more susceptible to type 2 diabetes, we estimated interaction terms for each factor and calculated weighted odds ratios. RESULTS: From 1998 to 2022, a consistent increase in the prevalence of type 2 diabetes was observed among South Koreans, with a notable rise to 15.61% (95% CI 14.83-16.38) during the pandemic. Awareness followed a U-shaped curve, bottoming out at 64.37% (95% CI 61.79-66.96) from 2013 to 2015 before increasing to 72.56% (95% CI 70.39-74.72) during the pandemic. Treatment also increased over time, peaking at 68.33% (95% CI 65.95-70.71) during the pandemic. Control among participants with diabetes showed no substantial change, maintaining a rate of 29.14% (95% CI 26.82-31.47) from 2020 to 2022, while control among treated participants improved to 30.68% (95% CI 27.88-33.48). During the pandemic, there was a steepening of the curves for awareness and treatment. However, while the slope of control among participants being treated increased, the slope of control among participants with diabetes showed no substantial change during the pandemic. Older populations and individuals with lower educational level exhibited less improvement in awareness and control trends than younger populations and more educated individuals. People with lower income experienced a deceleration in prevalence during the pandemic. CONCLUSIONS: Over the recent decade, there has been an increase in type 2 diabetes prevalence, awareness, treatment, and control. During the pandemic, a steeper increase in awareness, treatment, and control among participants being treated was observed. However, there were heterogeneous changes across different population groups, underscoring the need for targeted interventions to address disparities and improve diabetes management for susceptible populations.

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Background/Aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of long COVID in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary outcomes and other digestive abnormalities in various follow-up periods. Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years, including those with SARS-CoV-2 infection between 2020 and 2021 matched to non-infected control patients. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with contemporary controls. Results: The discovery cohort, consisting of 10,027,506 individuals (mean age 48.4 years; 49.9% female), revealed heightened risks of gastrointestinal diseases (HR: 1.15; 95% CI: 1.08-1.22), hepatobiliary diseases (1.30; 1.09-1.55), and other digestive abnormalities (1.05; 1.01-1.10) beyond the first 30 days after infection, following exposure-driven propensity score-matching. These results indicate a pronounced association as the severity of COVID-19 increases. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. Over time, the risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort. Conclusions: The incidences of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.

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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, a global health crisis, profoundly impacted all aspects of daily life. Adolescence, a pivotal stage of psychological and social development, is heavily influenced by the psychosocial and socio-cultural context. Hence, it is imperative to thoroughly understand the psychosocial changes adolescents experienced during the pandemic and implement effective management initiatives. DATA SOURCES: We examined the incidence rates of depressive and anxiety disorders among adolescents aged 10-19 years globally and regionally. We utilized data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to compare pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Our investigation covered 204 countries and territories across the six World Health Organization regions. We conducted a comprehensive literature search using databases including PubMed/MEDLINE, Scopus, and Google Scholar, employing search terms such as "psychosocial", "adolescent", "youth", "risk factors", "COVID-19 pandemic", "prevention", and "intervention". RESULTS: During the pandemic, the mental health outcomes of adolescents deteriorated, particularly in terms of depressive and anxiety disorders. According to GBD 2021, the incidence rate of anxiety disorders increased from 720.26 [95% uncertainty intervals (UI) = 548.90-929.19] before the COVID-19 pandemic (2018-2019) to 880.87 per 100,000 people (95% UI = 670.43-1132.58) during the COVID-19 pandemic (2020-2021). Similarly, the incidence rate of major depressive disorder increased from 2333.91 (95% UI = 1626.92-3138.55) before the COVID-19 pandemic to 3030.49 per 100,000 people (95% UI = 2096.73-4077.73) during the COVID-19 pandemic. This worsening was notably pronounced in high-income countries (HICs). Rapid environmental changes, including heightened social anxiety, school closures, economic crises, and exacerbated racism, have been shown to adversely affect the mental well-being of adolescents. CONCLUSIONS: The abrupt shift to remote learning and the absence of in-person social interactions heightened feelings of loneliness, anxiety, sadness, and stress among adolescents. This change magnified existing socioeconomic disparities, posing additional challenges. These complexities profoundly impact adolescents' well-being, especially vulnerable groups like those from HICs, females, and minorities. Acknowledging the underreporting bias in low- to middle-income countries highlights the importance of addressing these mental health alterations in assessments and interventions within these regions as well. Urgent interventions are crucial as the pandemic-induced mental stress may have lasting effects on adolescents' mental health.

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Vaccine-associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large-scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long-term trends, and potential risk factors of vaccines-associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all-cause rheumatic diseases, 14 703 reports of vaccine-associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID-19 mRNA vaccine-associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC025, 1.90), followed by COVID-19 mRNA (ROR, 2.79; IC025, 1.25), anthrax (ROR, 2.52; IC025, 0.76), papillomavirus (ROR, 2.16; IC025, 0.95), encephalitis (ROR, 2.01; IC025, 0.58), typhoid (ROR, 1.91; IC025, 0.44), influenza (ROR, 1.49; IC025, 0.46), and HAV vaccines (ROR, 1.41; IC025, 0.20). From age- and sex-specific perspective, young females and old males are likely to have vaccine-associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC025, 3.13) and Sjögren's syndrome (IC025, 0.70), systemic scleroderma (IC025, 0.64), specifically while the COVID-19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID-19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians.

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BACKGROUND: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled. OBJECTIVE: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence. METHODS: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or cross-sectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant. RESULTS: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69-5.17]; CE=suggestive), Parkinson's disease (3.35 [1.72-6.53]; CE=suggestive), asthma (1.86 [1.42-2.42]; CE=weak), toxoplasmosis (1.69 [1.21-2.37]; CE=weak), hypertension (1.28 [1.02-1.60]; CE=convincing), breast cancer (1.33 [1.15-1.55]; CE=weak), obesity (1.64 [1.30-1.99]; CE=suggestive), and type 2 diabetes mellitus (1.98 [1.55-2.52]; CE=weak). CONCLUSION: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them.

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Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

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BACKGROUND: We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS: We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION: We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.

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BACKGROUND: Understanding the association between hypertension prevalence and socioeconomic and behavioral variables during a pandemic is essential, and this analysis should extend beyond short-term trends. OBJECTIVE: This study aims to examine long-term trends in the prevalence of participants diagnosed with and receiving treatment for hypertension, using data collected by a nationally representative survey from 2009 to 2022, which includes the COVID-19 pandemic era. METHODS: A nationwide, population-based, cross-sectional study used data collected from the South Korea Community Health Survey between 2009 and 2022. The study sample comprised 3,208,710 Korean adults over a period of 14 years. We aimed to assess trends in the prevalence of participants diagnosed with and receiving treatment for hypertension in the national population from 2009 to 2022, with a specific focus on the COVID-19 pandemic, using weighted linear regression models. RESULTS: Among the included 3,072,546 Korean adults, 794,239 (25.85%) were aged 19-39 years, 1,179,388 (38.38%) were aged 40-59 years; 948,097 (30.86%) were aged 60-79 years, and 150,822 (4.91%) were aged 80 years or older. A total of 1,426,379 (46.42%) were men; 761,896 (24.80%) and 712,264 (23.18%) were diagnosed with and received treatment for hypertension, respectively. Although the overall prevalence over the 14-year period increased, the upward trends of patients diagnosed with and receiving treatment for hypertension decreased during the COVID-19 pandemic era compared with the prepandemic era (ß difference for trend during vs before the pandemic -.101, 95% CI -0.107 to -0.094 vs -.133, 95% CI -0.140 to -0.127). Notably, the trends in prevalence during the pandemic were less pronounced in subgroups of older adults (≥60 years old) and individuals with higher alcohol consumption (≥5 days/month). CONCLUSIONS: This nationwide representative study found that the national prevalence of participants diagnosed with and receiving treatment for hypertension increased during the prepandemic era. However, there was a marked decrease in these trends during the prepandemic era, compared with the pandemic era, particularly among specific subgroups at increased risk of negative outcomes. Future studies are needed to evaluate the factors associated with changes in the prevalence of hypertension during the COVID-19 pandemic.

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AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.

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Due to the limitation of previous studies examining adverse reports of myocarditis and pericarditis associated with vaccines other than the COVID-19 vaccine, there are challenges in establishing a comprehensive understanding of vaccine safety on a global scale. Hence, the objective of this study was to examine the worldwide burden of vaccine-associated pericarditis and myocarditis and the vaccines associated with these indications. This study utilized the World Health Organization international pharmacovigilance database, from which records of vaccine-associated pericarditis and myocarditis between 1969 and 2023 were extracted (over 130 million reports). We calculated global reporting counts, reported odds ratios (RORs), and information components (ICs) to discern the association between 19 vaccines and the occurrence of pericarditis and myocarditis across 156 countries and territories. We identified 49 096 reports (male, n = 30 013) of vaccine-associated pericarditis and myocarditis among 73 590 reports of all-cause pericarditis and myocarditis. There has been a significant increase in reports of vaccine-related cardiac adverse events over time, with a noteworthy surge observed after 2020, attributed to cases of pericarditis associated with COVID-19 mRNA vaccines. Smallpox vaccines were associated with most pericarditis and myocarditis reports (ROR: 73.68 [95% CI, 67.79-80.10]; IC [IC0.25]: 6.05 [5.91]), followed by COVID-19 mRNA vaccine (37.77 [37.00-38.56]; 3.07 [3.05]), anthrax vaccine (25.54 [22.37-29.16]; 4.58 [4.35]), typhoid vaccine (6.17 [5.16-7.38]; 2.59 [2.29]), encephalitis vaccine (2.00 [1.48-2.71]; 0.99 [0.47]), influenza vaccine (1.87 [1.71-2.04]; 0.90 [0.75]), and Ad5-vectored COVID-19 vaccine (1.40 [1.34-1.46]; 0.46 [0.39]). Concerning age and sex-specific risks, reports of vaccine-associated pericarditis and myocarditis were more prevalent among males and in older age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (median time: 1 day) and fatality rate was 0.44%. Our analysis of global data revealed an increase in pericarditis and myocarditis reports associated with vaccines, particularly live vaccines like smallpox and anthrax, notably in young males. While these adverse events are generally rare and mild, caution is warranted, especially for healthcare workers, due to potential myocardial injury-related in-hospital mortality. Further study with validated reporting is crucial to enhance accuracy in evaluating the correlation between vaccines and cardiac conditions for preventive measures.

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OBJECTIVE: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. METHODS: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. RESULTS: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). CONCLUSION: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.

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Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.

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Although only Saccharomyces boulardii has been studied for ulcerative colitis (UC), probiotic yeasts have immense therapeutic potential. Herein, we evaluated the kefir yeast Kluyveromyces marxianus A4 (Km A4) and its anti-inflammatory effect with sulfasalazine in BALB/c mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration continued for 7 days after the mice were randomly divided into seven groups: control (CON, normal mice administered with saline), DSS-induced colitis mice administered saline (DSS), and DSS-induced colitis mice administered sulfasalazine only (S), Km A4 only (A4), Km A4 plus sulfasalazine (A4 + S), S. boulardii ATCC MYA-796 (Sb MYA-796) only (Sb), and Sb MYA-796 plus sulfasalazine (Sb + S). The ß-glucan content of Km A4 was significantly higher than that of Sb MYA-796 (P < 0.05). Body weight gain (BWG) significantly correlated with colon length, cyclooxygenase-2 (Cox-2) levels, and Bacteroides abundance (P < 0.05). In colitis-induced mice, the A4 + S group had the lowest histological score (6.00) compared to the DSS group (12.67), indicating the anti-inflammatory effects of this combination. The A4 + S group showed significantly downregulated expression of interleukin (Il)-6, tumor necrosis factor-α (Tnf-α), and Cox-2 and upregulated expression of Il-10 and occludin (Ocln) compared to the DSS group. Mice treated with A4 + S had enhanced Bacteroides abundance in their gut microbiota compared with the DSS group (P < 0.05). Bacteroides were significantly correlated with all colitis biomarkers (BWG, colon length, Il-6, Tnf-α, Il-10, Cox-2, and Ocln; P < 0.05). The anti-inflammatory effects of Km A4 could be attributed to high ß-glucan content and gut microbiota modulation. Thus, treatment with Km A4 and sulfasalazine could alleviate UC.

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Although CRISPR-dCas13, the RNA-guided RNA-binding protein, was recently exploited as a translation-level gene expression modulator, it has still been difficult to precisely control the level due to the lack of detailed characterization. Here, we develop a synthetic tunable translation-level CRISPR interference (Tl-CRISPRi) system based on the engineered guide RNAs that enable precise and predictable down-regulation of mRNA translation. First, we optimize the Tl-CRISPRi system for specific and multiplexed repression of genes at the translation level. We also show that the Tl-CRISPRi system is more suitable for independently regulating each gene in a polycistronic operon than the transcription-level CRISPRi (Tx-CRISPRi) system. We further engineer the handle structure of guide RNA for tunable and predictable repression of various genes in Escherichia coli and Vibrio natriegens. This tunable Tl-CRISPRi system is applied to increase the production of 3-hydroxypropionic acid (3-HP) by 14.2-fold via redirecting the metabolic flux, indicating the usefulness of this system for the flux optimization in the microbial cell factories based on the RNA-targeting machinery.

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Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-ß and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-ß. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers. [BMB Reports 2024; 57(7): 318-323].

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Previous studies have examined the prevalence of allergic diseases in adolescents 1-2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the ß difference (ßdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 6.89% (95% CI 6.72-7.05) in 2018-2019, then decreased slightly to 5.82% (95% CI 5.60-6.04) in 2022. Across the 14 years, middle school student status, low parent's highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.

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