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.

Internet of Things-Enabled Patch With Built-in Microsensors and Wireless Chip: Real-Time Remote Monitoring of Patch Treatment.

Purpose: We aimed to design, develop, and evaluate an internet of things-enabled patch (IoT patch) for real-time remote monitoring of adherence (or patch wear time) during patch treatment in child participants in clinical trials. This study provides healthcare providers with a tool for objective, real-time, and remote assessment of adherence and for making required adjustments to treatment plans. Methods: The IoT patch had two temperature microsensors and a wireless chip. One sensor was placed closer to the skin than the other, resulting in a temperature difference depending on whether the patch was worn. When the patch was worn, it measured temperatures every 30 seconds and transmitted temperature data to a cloud server via a mobile application every 15 seconds. The patch was evaluated via 2 experiments with 30 healthy adults and 40 children with amblyopia. Results: Excellent monitoring accuracy was observed in both adults (mean delay of recorded time data, 0.4 minutes) and children (mean, 0.5 minutes). The difference between manually recorded and objectively recorded patch wear times showed good agreement in both groups. Experiment 1 showed accurate monitoring over a wide range of temperatures (from 0 to 30°C). Experiment 2 showed no significant differences in wearability (ease-of-use and comfort scores) between the IoT and conventional patches. Conclusions: The IoT patch offers an accurate, real-time, and remote system to monitor adherence to patch treatment. The patch is comfortable and easy to use. The utilization of an IoT patch may increase adherence to patch treatment based on accurate monitoring. Translational Relevance: Results show that the IoT patch can enable real-time adherence monitoring in clinical trials, improving treatment precision, and patient compliance to enhance outcomes.

Acute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan.

Considering the significant burden of post-acute COVID-19 conditions among patients infected with SARS-CoV-2, we aimed to identify the risk of acute respiratory complications or post-acute respiratory sequelae. A binational population-based cohort study was conducted to analyze the risk of acute respiratory complications or post-acute respiratory sequelae after SARS-CoV-2 infection. We used a Korean nationwide claim-based cohort (K-COV-N; n = 2,312,748; main cohort) and a Japanese claim-based cohort (JMDC; n = 3,115,606; replication cohort) after multi-to-one propensity score matching. Among 2,312,748 Korean participants (mean age, 47.2 years [SD, 15.6]; 1,109,708 [48.0%] female), 17.1% (394,598/2,312,748) were infected with SARS-CoV-2. The risk of acute respiratory complications or post-acute respiratory sequelae is significantly increased in people with SARS-CoV-2 infection compared to the general population (acute respiratory complications: HR, 8.06 [95% CI, 6.92-9.38]; post-acute respiratory sequelae: 1.68 [1.62-1.75]), and the risk increased with increasing COVID-19 severity. We identified COVID-19 vaccination as an attenuating factor, showing a protective association against acute or post-acute respiratory conditions. Furthermore, while the excess post-acute risk diminished with time following SARS-CoV-2 infection, it persisted beyond 6 months post-infection. The replication cohort showed a similar pattern in the association. Our study comprehensively evaluates respiratory complications in post-COVID-19 conditions, considering attenuating factors such as vaccination status, post-infection duration, COVID-19 severity, and specific respiratory conditions.

National trends in counseling for stress and depression and COVID-19 pandemic-related factors among adults, 2009-2022: A nationwide study in South Korea: Stress, depression, and pandemic.

To investigate the long-term trends in counseling for stress and depression using data from a nationwide survey in South Korea. We conducted a nationwide serial, large-scale, cross-sectional, survey-based study using data from 2,903,887 Korean adults from the Korea Community Health Survey, 2009-2022. Our study investigated the trends and risk factors for counseling for stress and depression during the pre-pandemic (2009-2019) and pandemic era (2020-2022). The prevalence of counseling for stress and depression increased across pre-pandemic (counseling for stress: ß, 0.217 [95 % CI, 0.194 to 0.241]; counseling for depression: ß, 0.136 [0.118 to 0.154]) and pandemic periods (ß, 0.324 [0.287 to 0.360]; ß, 0.210 [0.182 to 0.239], respectively). The prevalence of counseling for stress and depression showed steeper slopes for increasing trends after the outbreak. In addition, subgroups with female sex, urban residence, lower household income, lower self-rated health, shorter sleep time, and higher worries about contracting COVID-19 were the risk factors associated with the increased prevalence of counseling for stress and depression. Our study analyzed the trends in counseling for stress and depression among over two million South Korean adults in 2009-2022, revealing a significant escalation during the pandemic. These findings emphasize the need for mental health policies to support vulnerable groups during the pandemic.

Global burden of vaccine-associated multiple sclerosis, 1967-2022: A comprehensive analysis of the international pharmacovigilance database.

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.

Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK.

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020-2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13-1.27), notably in asthma (HR, 2.25; 95% CI, 1.80-2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15-1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68-0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.

National prevalence of smoking among adolescents at tobacco tax increase and COVID-19 pandemic in South Korea, 2005-2022.

Prior research has predominantly focused on the overall effects of the tobacco tax increase and the COVID-19 pandemic on adolescent smoking behavior. However, there is a need to examine both the immediate and sustained associations of these two factors on subgroups of adolescents, employing an interrupted time-series model. We aimed to investigate the immediate and sustained association of tobacco tax increase and the COVID-19 pandemic on adolescent smoking prevalence. This study utilized data from the Korea Youth Risk Behavior Web-Based Survey to analyze the prevalence of current smoking among all participants (CSP) and the prevalence of daily smoking among current smokers (DSP) of Korean adolescents (n = 1,159,995; mean, age 14.99; male 51.5%) over 18 years from 2005 to 2022. The study examined 18-year trends in CSP and DSP among Korean adolescents, emphasizing the influences of the 2015 tobacco tax increase and the COVID-19 pandemic, using ß coefficients and their differences (ßdiff) from an interrupted time-series ARIMA model. While CSP exhibited a decreasing trend, DSP exhibited an increasing trend. Tobacco tax increase was associated with both the short and long terms in smoking prevalence, however, the short-term association on prevalence (CSP, - 3.076 [95% CI, - 3.707 to - 2.445]; DSP, - 4.112 [95% CI, - 6.488 to - 1.735]) was stronger. The pandemic was associated with an immediate increase in DSP (9.345 [95% CI, 5.285-13.406]). These effects were strongest among adolescents from low economic status and those exposed to familial secondhand smoking. Supportive programs for adolescents in low-income families will help overcome the effects associated with the pandemic. As a tobacco tax increase was associated with a reduction in smoking prevalence, this could be one method to overcome the effects of the pandemic.

Cheonwangbosimdan mitigates post-traumatic stress disorder-like behaviors through GluN2B-containing NMDA receptor antagonism in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects. AIM OF THE STUDY: The purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study. MATERIALS AND METHODS: A single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors. RESULTS: CWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction. CONCLUSIONS: CWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies.

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.

D-Pinitol mitigates post-traumatic stress disorder-like behaviors induced by single prolonged stress in mice through mineralocorticoid receptor antagonism.

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of D-pinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor.

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

BACKGROUND: There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. METHODS: Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. RESULTS: During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. CONCLUSION: This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.

Global trends in incidence and prevalence of achalasia, 1925-2021: A systematic review and meta-analysis.

BACKGROUND: Achalasia poses a significant socioeconomic burden, yet global trends remain undocumented. This study aims to describe the worldwide trends in the incidence and prevalence of achalasia from 1925 to 2021 and explore their correlation with various factors through a comprehensive systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases from inception to 30 June 2023, to identify studies reporting the incidence or prevalence of achalasia in the general population. This study utilized pooled estimates with 95% confidence intervals (CI) to estimate the incidence and prevalence of achalasia, and conducted various subgroup analyses. RESULTS: A total of 26 eligible studies covering approximately 269 million participants and 20,873 patients from 14 countries across five continents were included. Global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person-years (95% CI, 0.64-0.93; number of studies, 26; sample population, 269,315,171) and 10.82 cases per 100,000 person-years (95% CI, 8.15-13.48; number of studies, 14; sample population, 192,176,076), respectively. The incidence of achalasia was higher in Oceania (than Asia and Africa) and in adults (than children) after the introduction of the Chicago classification. Prevalence followed a similar pattern. The pooled incidence of achalasia showed an overall upward trend from 1925 to 2021 (1925-1999; 0.40 [0.32-0.49] vs. 2018-2021; 1.64 [1.33-1.95] cases per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of achalasia have notably increased, particularly with advancements in diagnosis, and show significant variation worldwide, despite the large heterogeneity within the sample population. Further studies are necessary to accurately assess the global incidence and prevalence of achalasia.

Paeonol alleviates postmenopause-induced neuropsychiatric symptoms through the modulation of GPR30 in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Moutan cortex (MC), the root bark of Paeonia suffruticosa Anderws (Paeoniaceae), has been historically employed in traditional herbal medicine for addressing women's ailments by replenishing kidney Yin. AIM OF THE STUDY: We aimed to explore if paeonol, an active constituent of MC, could ameliorate neuropsychiatric symptoms, such as anxiety, depression, and cognitive impairments, associated with post-menopausal syndrome (PMS) in an ovariectomized (OVX) mouse model. MATERIALS AND METHODS: The experimental design comprised 6 groups, including a sham group, OVX group, paeonol administration groups (3, 10 or 30 mg/kg, p.o.), and an estradiol (E2)-treated positive control group. Behavioral tests including the open field, novel object recognition, Y-maze, elevated plus-maze, splash, and forced swimming tests were conducted. In addition, we investigated the effets of paeonol on the phosphorylated levels of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as on the expression levels of G protein-coupled receptor (GPR30) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus. RESULTS: Paeonol treatment (10 and 30 mg/kg, p.o.) effectively reversed the cognitive decline in OVX mice, measured by the novel object recognition and Y-maze tests, similar to that in the positive control group. Additionally, it alleviated anxiety- and depressive-like behaviors, as evaluated by the elevated plus-maze test, splash test, and forced swimming test. Paeonol restored GPR30 expression levels in the prefrontal cortex and hippocampus, mirroring the effects of E2 administration. Furthermore, it reversed the reduced expression levels of the PI3K-Akt-mTOR signaling pathway in the prefrontal cortex and hippocampus and increased BDNF expression in the hippocampus of OVX mice. CONCLUSION: This research suggests that paeonol would be beneficial for alleviating PMS-associated cognitive impairment, anxiety and depression.

Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

BACKGROUND: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. METHODS: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. RESULTS: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. CONCLUSIONS: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Limitations of the Cough Sound-Based COVID-19 Diagnosis Artificial Intelligence Model and its Future Direction: Longitudinal Observation Study.

BACKGROUND: The outbreak of SARS-CoV-2 in 2019 has necessitated the rapid and accurate detection of COVID-19 to manage patients effectively and implement public health measures. Artificial intelligence (AI) models analyzing cough sounds have emerged as promising tools for large-scale screening and early identification of potential cases. OBJECTIVE: This study aimed to investigate the efficacy of using cough sounds as a diagnostic tool for COVID-19, considering the unique acoustic features that differentiate positive and negative cases. We investigated whether an AI model trained on cough sound recordings from specific periods, especially the early stages of the COVID-19 pandemic, were applicable to the ongoing situation with persistent variants. METHODS: We used cough sound recordings from 3 data sets (Cambridge, Coswara, and Virufy) representing different stages of the pandemic and variants. Our AI model was trained using the Cambridge data set with subsequent evaluation against all data sets. The performance was analyzed based on the area under the receiver operating curve (AUC) across different data measurement periods and COVID-19 variants. RESULTS: The AI model demonstrated a high AUC when tested with the Cambridge data set, indicative of its initial effectiveness. However, the performance varied significantly with other data sets, particularly in detecting later variants such as Delta and Omicron, with a marked decline in AUC observed for the latter. These results highlight the challenges in maintaining the efficacy of AI models against the backdrop of an evolving virus. CONCLUSIONS: While AI models analyzing cough sounds offer a promising noninvasive and rapid screening method for COVID-19, their effectiveness is challenged by the emergence of new virus variants. Ongoing research and adaptations in AI methodologies are crucial to address these limitations. The adaptability of AI models to evolve with the virus underscores their potential as a foundational technology for not only the current pandemic but also future outbreaks, contributing to a more agile and resilient global health infrastructure.

National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

INTRODUCTION: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. METHOD: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained ß-coefficients with 95% confidence intervals (CI). RESULTS: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. CONCLUSIONS: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.