Associations between vision impairment and eye diseases with dementia, dementia subtypes and cognitive impairment: An umbrella review.

Vision impairment (VI) and eye diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataract have been reported to be associated with cognitive impairment and dementia, however, to date, very little attempt has been made to collate and synthesizes such literature. Therefore, the aim of this umbrella review is to systematically assesses the credibility and certainty of evidence of associations between vision impairment (VI) and eye diseases with cognitive impairment, dementia and dementia subtypes. We conducted an umbrella review of meta-analyses by screening articles in any language in PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL and CDSR published from database inception up to May 30, 2024. Quality appraisal of each included original meta-analysis was assessed using A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2). The certainty of the evidence was based on statistical significance, study size, heterogeneity, small study effects, prediction intervals (PI), and bias. We followed an a-priori protocol registered with PROSPERO (CRD42024564249). We identified 13 meta-analyses (AMSTAR 2; high accuracy of the findings 1, moderate 10, and low 2) that included 232 original articles based on 99,337,354 participants. Overall, no evidence was highly suggestive or convincing. Suggestive evidence was found for associations between cataract and dementia (equivalent odds ratio [eOR] 1.20, 95 %CI, 1.16-1.25), cataract and Alzheimer's disease (eOR 1.21, 95 %CI, 1.15-1.28), and AMD and Alzheimer's disease (eOR 1.27, 95 %CI, 1.27-1.27). Weak evidence was found for associations between VI and dementia (eOR 1.50, 95 %CI, 1.23-1.84), DR and dementia (eOR 1.33, 95 %CI, 1.17-1.50), cataract and vascular dementia (eOR 1.26, 95 %CI, 1.09-1.45), VI identified by cross-sectional studies and cognitive impairment (eOR 2.37, 95 %CI, 2.31-2.44), and VI identified by objective measures and cognitive impairment (eOR 1.56, 95 %CI, 1.12-2.18). The observed suggestive level of evidence for the relationship between eye disease and dementia (as well as dementia subtypes) suggests that policy and interventions to aid in the prevention and management of eye disease may also aid in the prevention of dementia syndrome. Where the level of evidence is weak, further studies are needed with stronger methodological approaches.

National Trends in the Prevalence of Self-Perceived Overweight Among Adolescents Between 2005 and 2022: Nationwide Representative Study.

BACKGROUND: Despite several studies on self-evaluation of health and body shape, existing research on the risk factors of self-perceived overweight is insufficient, especially during the COVID-19 pandemic. OBJECTIVE: This study aims to identify the risk factors affecting self-perceived overweight and examine how the prevalence of self-perceived overweight has changed before and during the COVID-19 pandemic. Specifically, we analyzed the impact of altered lifestyles due to COVID-19 on this phenomenon. METHODS: The data used in the study were obtained from middle and high school students who participated in the Korean Youth Risk Behavior Web-based Survey (N=1,189,586). This survey was a 2-stage stratified cluster sampling survey representative of South Korean adolescents. We grouped the survey results by year and estimated the slope in the prevalence of self-perceived overweight before and during the pandemic using weighted linear regression, as well as the prevalence tendencies of self-perceived overweight according to various risk factors. We used prevalence ratios to identify the risk factors for self-perceived overweight. In addition, we conducted comparisons of risk factors in different periods to identify their associations with the COVID-19 pandemic. RESULTS: The prevalence of self-perceived overweight was much higher than BMI-based overweight among 1,189,586 middle and high school participants (grade 7-12) from 2005 to 2022 (female participants: n=577,102, 48.51%). From 2005 to 2019 (prepandemic), the prevalence of self-perceived overweight increased (ß=2.80, 95% CI 2.70-2.90), but from 2020 to 2022 (pandemic) it decreased (ß=-0.53, 95% CI -0.74 to -0.33). During the pandemic, individuals with higher levels of stress or lower household economic status exhibited a more substantial decrease in the rate of self-perceived overweight. The prevalence of self-perceived overweight tended to be higher among individuals with poor academic performance, lower economic status, poorer subjective health, and a higher stress level. CONCLUSIONS: Our nationwide study, conducted over 18 years, indicated that self-perceived overweight decreased during the COVID-19 period while identifying low academic performance and economic status as risk factors. These findings suggest the need for policies and facilities to address serious dieting and body dissatisfaction resulting from self-perceived overweight by developing counseling programs for adolescents with risk factors such as lower school performance and economic status.

Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced immunotherapy.

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ±â€¯1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.

Age-related changes in connected speech production: evidence from eye-tracking in the culturally adapted picture description task.

Purpose: Age-related changes in connected speech production remain a subject of debate, yielding inconsistent findings across various tasks and measures. This study aimed to investigate the effects of aging on picture description tasks using two types of pictures: a standardized picture (the Beach picture) and a culturally and linguistically modified picture tailored for Korean speakers (the Han River picture). Method: Twenty-four young adults and 22 older adults participated in two picture description tasks while their eye movements were recorded. Word-level linguistic variables were used to assess informativeness (Correct Information Units per minute) and productivity (noun and verb counts per utterance) of connected speech production. Eye-movement measures were employed to evaluate real-time cognitive processing associated with planning connected speech (pre-speech fixation counts and durations; eye fixations before the speech onset of each utterance). Results and conclusions: The findings revealed age-related declines in linguistic measures, with older adults exhibiting decreased CIUs per minute and smaller counts of nouns and verbs per utterance. Age-related changes in eye movement measures were evident in that older adults displayed longer pre-speech fixation durations. Unlike younger adults, older adults exhibited higher pre-speech fixation counts on the Han River picture compared to the Beach picture, suggesting cognitive challenges in performing the task that requires producing more words and detailed descriptions. These results suggest that aging is associated with reduced informativeness and productivity of connected speech, as well as a decline in cognitive processing efficiency.

Global burden of vaccine-associated rheumatic diseases and their related vaccines, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

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.

Biomarkers and Related Factors for the Diagnosis, Risk of Coronary Artery Lesions, and Resistance to Intravenous Immunoglobulin in Kawasaki Disease: An Umbrella Review of Meta-Analyses.

Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 [95% CI, 13.58-27.56]), Serum ferritin (DOR, 24.90 [11.67-53.12]), N terminal proBNP (DOR, 21.03 [9.03-49.00]), and micro RNAs (DOR, 45.28 [6.30-325.52]), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 [95% CI, 2.37-25.09]), non-coding RNAs (DOR, 14.63 [3.24-66.14]), neutrophil to lymphocyte ratio (DOR, 6.62 [4.05-10.81]), platelet to lymphocyte ratio (DOR, 3.30 [2.10-5.19]), and C reactive protein (DOR, 6.58 [3.69-11.74]). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.

Comorbid physical health outcomes in patients with bipolar disorder: An umbrella review of systematic reviews and meta-analyses.

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.

Comorbid health conditions in people with attention-deficit/hyperactivity disorders: An umbrella review of systematic reviews and meta-analyses.

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.

Global public concern of childhood and adolescence suicide: a new perspective and new strategies for suicide prevention in the post-pandemic era.

BACKGROUND: Suicide is the second leading cause of death in young people worldwide and is responsible for about 52,000 deaths annually in children and adolescents aged 5-19 years. Familial, social, psychological, and behavioral factors play important roles in suicide risk. As traumatic events such as the COVID-19 pandemic may contribute to suicidal behaviors in young people, there is a need to understand the current status of suicide in adolescents, including its epidemiology, associated factors, the influence of the pandemic, and management initiatives. DATA SOURCES: We investigated global and regional suicide mortality rates among children and adolescents aged 5-19 years using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The suicide mortality rates from 1990 to 2019 were examined in 204 countries and territories across six World Health Organization (WHO) regions. Additionally, we utilized electronic databases, including PubMed/MEDLINE and Scopus, and employed various combinations of terms such as "suicide", "adolescents", "youth", "children", "risk factors", "COVID-19 pandemic", "prevention", and "intervention" to provide a narrative review on suicide within the pediatric population in the post-pandemic era. RESULTS: Despite the decreasing trend in the global suicide mortality rate from 1990 to 2019, it remains high. The mortality rates from suicide by firearms or any other specified means were both greater in males. Additionally, Southeast Asia had the highest suicide rate among the six WHO regions. The COVID-19 pandemic seems to contribute to suicide risk in young people; thus, there is still a strong need to revisit appropriate management for suicidal children and adolescents during the pandemic. CONCLUSIONS: The current narrative review integrates up-to-date knowledge on suicide epidemiology and the effects of the COVID-19 pandemic, risk factors, and intervention strategies. Although numerous studies have characterized trends in suicide among young people during the pre-pandemic era, further studies are required to investigate suicide during the pandemic and new strategies for suicide prevention in the post-pandemic era. It is necessary to identify effective prevention strategies targeting young people, particularly those at high risk, and successful treatment for individuals already manifesting suicidal behaviors. Care for suicidal children and adolescents should be improved with parental, school, community, and clinical involvement.

Global burden of anticancer drug-induced acute kidney injury and tubulointerstitial nephritis from 1967 to 2023.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

National and Regional Trends in the Prevalence of Hypertension in South Korea Amid the Pandemic, 2009-2022: Nationwide Study of Over 3 Million Individuals.

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.

Global estimates on the reports of vaccine-associated myocarditis and pericarditis from 1969 to 2023: Findings with critical reanalysis from the WHO pharmacovigilance database.

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.

Human dermal fibroblast-derived secretory proteins for regulating nerve restoration: A bioinformatic approach.

BACKGROUND: Human dermal fibroblasts secrete diverse proteins that regulate wound repair and tissue regeneration. METHODS: In this study, dermal fibroblast-conditioned medium (DFCM) proteins potentially regulating nerve restoration were bioinformatically selected among the 337 protein lists identified by quantitative liquid chromatography-tandem mass spectrometry. Using these proteins, protein-protein interaction network analysis was conducted. In addition, the roles of DFCM proteins were reviewed according to their protein classifications. RESULTS: Gene Ontology protein classification categorized these 57 DFCM proteins into various classes, including protein-binding activity modulator (N = 11), cytoskeletal protein (N = 8), extracellular matrix protein (N = 6), metabolite interconversion enzyme (N = 5), chaperone (N = 4), scaffold/adapter protein (N = 4), calcium-binding protein (N = 3), cell adhesion molecule (N = 2), intercellular signal molecule (N = 2), protein modifying enzyme (N = 2), transfer/carrier protein (N = 2), membrane traffic protein (N = 1), translational protein (N = 1), and unclassified proteins (N = 6). Further protein-protein interaction network analysis of 57 proteins revealed significant interactions among the proteins that varied according to the settings of confidence score. CONCLUSIONS: Our bioinformatic analysis demonstrated that DFCM contains many secretory proteins that form significant protein-protein interaction networks crucial for regulating nerve restoration. These findings underscore DFCM proteins' critical roles in various nerve restoration stages during the wound repair process.

Global association of secondhand smoke exposure locations and smoking behaviour among adolescents in 99 countries.

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.

Effects and safety of transcranial direct current stimulation on multiple health outcomes: an umbrella review of randomized clinical trials.

Transcranial direct current stimulation (tDCS), which delivers a direct current to the brain, emerged as a non-invasive potential therapeutic in treating a range of neurological and neuropsychiatric disorders. However, a comprehensive quantitative evidence synthesis on the effects of tDCS on a broad range of mental illnesses is lacking. Here, we systematically assess the certainty of the effects and safety of tDCS on several health outcomes using an umbrella review of randomized controlled trials (RCTs). The methodological quality of each included original meta-analysis was assessed by the A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2), and the certainty of the evidence for each effect was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). We followed an a priori protocol (PROSPERO CRD42023458700). We identified 15 meta-analyses of RCTs (AMSTAR 2; high 3, moderate 3, and low 9) that included 282 original articles, covering 22 unique health endpoints across 22 countries and six continents. From meta-analyses of RCTs supported by very low to high certainty of evidence, it was found that tDCS improved symptoms related to post-stroke, including post-stroke depression scale score (equivalent standardized mean difference [eSMD], 1.61 [95% confidence level, 0.72-2.50]; GRADE=moderate), activities of daily living independence (7.04 [3.41-10.67]; GRADE=high), motor recovery of upper and lower extremity (upper extremity: 0.15 [0.06-0.24], GRADE=high; lower extremity: 0.10 [0.03-0.16], GRADE=high), swallowing performance (GRADE=low), and spasticity (GRADE=moderate). In addition, tDCS had treatment effects on symptoms of several neurological and neuropsychiatric disorders, including obsessive-compulsive disorder (0.81 [0.44-1.18]; GRADE=high), pain in fibromyalgia (GRADE=low), disease of consciousness (GRADE=low), insight score (GRADE=moderate) and working memory (0.34 [0.01-0.67]; GRADE=high) in schizophrenia, migraine-related pain (-1.52 [-2.91 to -0.13]; GRADE=high), attention-deficit/hyperactivity disorder (reduction in overall symptom severity: 0.24 [0.04-0.45], GRADE=low; reduction in inattention: 0.56 [0.02-1.11], GRADE=low; reduction in impulsivity: 0.28 [0.04-0.51], GRADE=low), depression (GRADE=low), cerebellar ataxia (GRADE=low), and pain (GRADE=very low). Importantly, tDCS induced an increased number of reported cases of treatment-emergent mania or hypomania (0.88 [0.62-1.13]; GRADE=moderate). We found varied levels of evidence for the effects of tDCS with multiple neurological and neuropsychiatric conditions, from very low to high certainty of evidence. tDCS was effective for people with stroke, obsessive-compulsive disorder, fibromyalgia, disease of consciousness, schizophrenia, migraine, attention-deficit/hyperactivity disorder, depression, cerebellar ataxia, and pain. Therefore, these findings suggest the benefit of tDCS for several neurological and neuropsychiatric disorders; however, further studies are needed to understand the underlying mechanism and optimize its therapeutic potential.

National prevalence of atopic dermatitis in Korean adolescents from 2009 to 2022.

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.

Global and regional prevalence of polypharmacy and related factors, 1997-2022: An umbrella review.

OBJECTIVE: Limited comprehensive evidence exists on the global prevalence of polypharmacy. This knowledge gap contributes to increased healthcare system costs and related public health concerns. Thus, we aimed to synthesize the current evidence on polypharmacy prevalence and associated factors in the general and older populations using an umbrella review. METHODS: Our primary outcomes were global prevalence and related indicators of polypharmacy. We systematically searched Google Scholar, PubMed/MEDLINE, Embase, and CINAHL for studies published between the inception of each database until April 30, 2023. RESULTS: Eleven meta-analyses incorporating 295 studies and 59,552,762 participants from 41 countries across six continents were identified. The global prevalence of polypharmacy in the general population is 37 %, with higher rates in older individuals (45 %), outpatients (48 %), and inpatients (52 %). North America showed a higher prevalence (52 %) than Asia (36 %) and Europe (36 %). Among frail elderly individuals, the prevalence of polypharmacy is 59 %, with the highest rates in Europe (68 %) and hospital settings (71 %). CONCLUSION: The global prevalence of polypharmacy and its associated factors in older adults present a complex, multifaceted, and conflicting picture. Understanding the prevalence of polypharmacy and its associated factors may help reduce the number of multidrug prescriptions.

Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea.

OBJECTIVE: To investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children. DESIGN: Nationwide birth cohort study. SETTING: From 1 January 2009 to 31 December 2020, birth cohort data of pregnant women in South Korea linked to their liveborn infants from the National Health Insurance Service of South Korea were collected. PARTICIPANTS: All 3 251 594 infants (paired mothers, n=2 369 322; age 32.1 years (standard deviation 4.2)) in South Korea from the start of 2010 to the end of 2017, with follow-up from the date of birth until the date of death or 31 December 2020, were included. MAIN OUTCOME MEASURES: Diagnosis of neuropsychiatric disorders in liveborn infants with mental and behaviour disorders (International Classification of Diseases 10th edition codes F00-99). Follow-up continued until the first diagnosis of neuropsychiatric disorder, 31 December 2020 (end of the study period), or the date of death, whichever occurred first. Eight cohorts were created: three cohorts (full unmatched, propensity score matched, and child screening cohorts) were formed, all of which were paired with sibling comparison cohorts, in addition to two more propensity score groups. Multiple subgroup analyses were performed. RESULTS: Of the 3 128 571 infants included (from 2 299 664 mothers), we identified 2 912 559 (51.3% male, 48.7% female) infants with no prenatal opioid exposure and 216 012 (51.2% male, 48.8% female) infants with prenatal opioid exposure. The risk of neuropsychiatric disorders in the child with prenatal opioid exposure was 1.07 (95% confidence interval 1.05 to 1.10) for fully adjusted hazard ratio in the matched cohort, but no significant association was noted in the sibling comparison cohort (hazard ratio 1.00 (0.93 to 1.07)). Prenatal opioid exposure during the first trimester (1.11 (1.07 to 1.15)), higher opioid doses (1.15 (1.09 to 1.21)), and long term opioid use of 60 days or more (1.95 (1.24 to 3.06)) were associated with an increased risk of neuropsychiatric disorders in the child. Prenatal opioid exposure modestly increased the risk of severe neuropsychiatric disorders (1.30 (1.15 to 1.46)), mood disorders, attention deficit hyperactivity disorder, and intellectual disability in the child. CONCLUSIONS: Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring. A slightly increased risk of neuropsychiatric disorders was observed, but this should not be considered clinically meaningful given the observational nature of the study, and limited to high opioid dose, more than one opioid used, longer duration of exposure, opioid exposure during early pregnancy, and only to some neuropsychiatric disorders.

Prenatal and postnatal factors associated with sudden infant death syndrome: an umbrella review of meta-analyses.

BACKGROUND: Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome (SIDS) effects is lacking. We investigated the risk and protective factors related to SIDS. METHODS: We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors. PubMed/MEDLINE, Embase, EBSCO, and Google Scholar were searched from inception until January 18, 2023. Data extraction, quality assessment, and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines. According to observational evidence, credibility was graded and classified by class and quality of evidence (CE; convincing, highly suggestive, suggestive, weak, or not significant). Our study protocol was registered with PROSPERO (CRD42023458696). The risk and protective factors related to SIDS are presented as equivalent odds ratios (eORs). RESULTS: We identified eight original meta-analyses, including 152 original articles, covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents. Several risk factors, including prenatal drug exposure [eOR = 7.84 (95% CI = 4.81-12.79), CE = highly suggestive], prenatal opioid exposure [9.55 (95% CI = 4.87-18.72), CE = suggestive], prenatal methadone exposure [9.52 (95% CI = 3.34-27.10), CE = weak], prenatal cocaine exposure [4.38 (95% CI = 1.95-9.86), CE = weak], prenatal maternal smoking [2.25 (95% CI = 1.95-2.60), CE = highly suggestive], postnatal maternal smoking [1.97 (95% CI = 1.75-2.22), CE = weak], bed sharing [2.89 (95% CI = 1.81-4.60), CE = weak], and infants found with heads covered by bedclothes after last sleep [11.01 (95% CI = 5.40-22.45), CE = suggestive], were identified. On the other hand, three protective factors, namely, breastfeeding [0.57 (95% CI = 0.39-0.83), CE = non-significant], supine sleeping position [0.48 (95% CI = 0.37-0.63), CE = suggestive], and pacifier use [0.44 (95% CI = 0.30-0.65), CE = weak], were also identified. CONCLUSIONS: Based on the evidence, we propose several risk and protective factors for SIDS. This study suggests the need for further studies on SIDS-related factors supported by weak credibility, no association, or a lack of adequate research.

Machine Learning-Based Prediction of Suicidality in Adolescents With Allergic Rhinitis: Derivation and Validation in 2 Independent Nationwide Cohorts.

BACKGROUND: Given the additional risk of suicide-related behaviors in adolescents with allergic rhinitis (AR), it is important to use the growing field of machine learning (ML) to evaluate this risk. OBJECTIVE: This study aims to evaluate the validity and usefulness of an ML model for predicting suicide risk in patients with AR. METHODS: We used data from 2 independent survey studies, Korea Youth Risk Behavior Web-based Survey (KYRBS; n=299,468) for the original data set and Korea National Health and Nutrition Examination Survey (KNHANES; n=833) for the external validation data set, to predict suicide risks of AR in adolescents aged 13 to 18 years, with 3.45% (10,341/299,468) and 1.4% (12/833) of the patients attempting suicide in the KYRBS and KNHANES studies, respectively. The outcome of interest was the suicide attempt risks. We selected various ML-based models with hyperparameter tuning in the discovery and performed an area under the receiver operating characteristic curve (AUROC) analysis in the train, test, and external validation data. RESULTS: The study data set included 299,468 (KYRBS; original data set) and 833 (KNHANES; external validation data set) patients with AR recruited between 2005 and 2022. The best-performing ML model was the random forest model with a mean AUROC of 84.12% (95% CI 83.98%-84.27%) in the original data set. Applying this result to the external validation data set revealed the best performance among the models, with an AUROC of 89.87% (sensitivity 83.33%, specificity 82.58%, accuracy 82.59%, and balanced accuracy 82.96%). While looking at feature importance, the 5 most important features in predicting suicide attempts in adolescent patients with AR are depression, stress status, academic achievement, age, and alcohol consumption. CONCLUSIONS: This study emphasizes the potential of ML models in predicting suicide risks in patients with AR, encouraging further application of these models in other conditions to enhance adolescent health and decrease suicide rates.