3-Hydroxytanshinone Inhibits the Activity of Hypoxia-Inducible Factor 1-α by Interfering with the Function of α-Enolase in the Glycolytic Pathway.

Tumor cells in hypoxic conditions control cancer metabolism and angiogenesis by expressing HIF-1α. Tanshinone is a traditional Chinese medicine that has been shown to possess antitumor properties and exerts a therapeutic impact on angiogenesis. However, the precise molecular mechanism responsible for the antitumor activity of 3-Hydroxytanshinone (3-HT), a type of tanshinone, has not been fully understood. Therefore, our study aimed to investigate the mechanism by which 3-HT regulates the expression of HIF-1α. Our findings demonstrate that 3-HT inhibits HIF-1α activity and expression under hypoxic conditions. Additionally, 3-HT inhibits hypoxia-induced angiogenesis by suppressing the expression of VEGF. Moreover, 3-HT was found to directly bind to α-enolase, an enzyme associated with glycolysis, resulting in the suppression of its activity. This inhibition of α-enolase activity by 3-HT leads to the blockade of the glycolytic pathway and a decrease in glycolysis products, ultimately altering HIF1-α expression. Furthermore, 3-HT negatively regulates the expression of HIF-1α by altering the phosphorylation of AMP-activated protein kinase (AMPK). Our study's findings elucidate the mechanism by which 3-HT regulates HIF-1α through the inhibition of the glycolytic enzyme α-enolase and the phosphorylation of AMPK. These results suggest that 3-HT holds promise as a potential therapeutic agent for hypoxia-related angiogenesis and tumorigenesis.

Impact of sleep disturbance in shift workers on hippocampal volume and psychomotor speed.

STUDY OBJECTIVES: Shift work interferes with circadian rhythms, affecting sleep quality and cognitive function. Poor sleep quality in shift workers can impair psychomotor performance due to fatigue and sleepiness, increasing the risk of errors, accidents, and reduced productivity. Given the potential for atrophic changes in the hippocampus due to sleep disturbances, our study investigates how poor sleep quality correlates with hippocampal structural alterations and impacts psychomotor performance among shift workers. METHODS: We recruited 100 shift workers, classifying them based on sleep quality into two groups: good sleep-SW group (n = 59) and poor sleep-SW group (n = 41). Sleep quality was assessed using both 7-day actigraphy for sleep efficiency and the Pittsburgh Sleep Quality Index. A control group of 106 non-shift workers without sleep problems (non-SW group) was also included for comparison. The outcome measures were psychomotor speed and hippocampal volumes, both total and by subfield. RESULTS: The poor sleep-SW group showed significantly smaller hippocampal volumes than both the good sleep-SW group (P<0.001) and the non-SW group (P=0.003). Longer shift work years correlated with greater reductions in hippocampal volume in this group (r=-0.42, P=0.009), unlike in the good sleep-SW group (r=0.08, P=0.541). Furthermore, they demonstrated declines in psychomotor speed relative to the non-SW group (P=0.006), which correlated with smaller hippocampal volumes (r=0.37, P=0.020). CONCLUSIONS: Shift workers with poor sleep quality exhibit significant hippocampal volume reductions and psychomotor speed decline, underscoring the importance of early intervention and support for sleep issues in this population.

Associations between serum perfluoroalkyl and polyfluoroalkyl concentrations and diabetes mellitus in the Korean general population: Insights from the Korean National Environmental Health Survey 2018-2020.

AIMS: Recent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. METHODS: We analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018-2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7-6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. RESULTS: In the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. CONCLUSIONS: These findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.

Associations between Urinary Mercury/Cadmium Concentrations and Anthropometric Features in Korean Children.

Investigating the impact of urinary mercury and cadmium on anthropometric parameters in Korean children is crucial amid growing concerns about heavy metal exposure and childhood growth. Using data from the Korean National Environmental Health Survey (2015-2017), we assessed age- and sex-specific associations of urinary mercury and cadmium with height and body mass index (BMI) z-scores in 1458 children aged 3-5 (n = 571) and 6-11 years (n = 887). Overall, 5.0% had stunted height (3-5 years: 6.9%, 6-11 years: 3.8%), whereas older children exhibited higher overweight/obesity prevalence (29.2%) than younger ones did (22.2%). In 3-5-year-old boys, urinary mercury correlated negatively with height z-scores (p < 0.001), whereas in girls, urinary cadmium correlated positively (p = 0.015). Boys aged 6-11 years showed positive associations between mercury/cadmium levels and BMI z-scores (p = 0.012). Logistic regression indicated associations between urinary mercury and stunted height likelihood (p = 0.001) and between urinary cadmium and reduced overweight likelihood (p = 0.039) in 3-5-year-old boys. In boys aged 6-11 years, urinary cadmium levels were positively associated with overweight likelihood (p = 0.003). This study underscores the link between elevated urinary mercury, cadmium levels, and growth disruptions in Korean children, emphasizing the need for public health strategies for reducing childhood heavy metal exposure.

Risk of hospital admission and death from first-ever SARS-CoV-2 infection by age group during the Delta and Omicron periods in British Columbia, Canada.

BACKGROUND: Population-based cross-sectional serosurveys within the Lower Mainland, British Columbia, Canada, showed about 10%, 40% and 60% of residents were infected with SARS-CoV-2 by the sixth (September 2021), seventh (March 2022) and eighth (July 2022) serosurveys. We conducted the ninth (December 2022) and tenth (July 2023) serosurveys and sought to assess risk of severe outcomes from a first-ever SARS-CoV-2 infection during intersurvey periods. METHODS: Using increments in cumulative infection-induced seroprevalence, population census, discharge abstract and vital statistics data sets, we estimated infection hospitalization and fatality ratios (IHRs and IFRs) by age and sex for the sixth to seventh (Delta/Omicron-BA.1), seventh to eighth (Omicron-BA.2/BA.5) and eighth to ninth (Omicron-BA.5/BQ.1) intersurvey periods. As derived, IHR and IFR estimates represent the risk of severe outcome from a first-ever SARS-CoV-2 infection acquired during the specified intersurvey period. RESULTS: The cumulative infection-induced seroprevalence was 74% by December 2022 and 79% by July 2023, exceeding 80% among adults younger than 50 years but remaining less than 60% among those aged 80 years and older. Period-specific IHR and IFR estimates were consistently less than 0.3% and 0.1% overall. By age group, IHR and IFR estimates were less than 1.0% and up to 0.1%, respectively, except among adults aged 70-79 years during the sixth to seventh intersurvey period (IHR 3.3% and IFR 1.0%) and among those aged 80 years and older during all periods (IHR 4.7%, 2.2% and 3.5%; IFR 3.3%, 0.6% and 1.3% during the sixth to seventh, seventh to eighth and eighth to ninth periods, respectively). The risk of severe outcome followed a J-shaped age pattern. During the eighth to ninth period, we estimated about 1 hospital admission for COVID-19 per 300 newly infected children younger than 5 years versus about 1 per 30 newly infected adults aged 80 years and older, with no deaths from COVID-19 among children but about 1 death per 80 newly infected adults aged 80 years and older during that period. INTERPRETATION: By July 2023, we estimated about 80% of residents in the Lower Mainland, BC, had been infected with SARS-CoV-2 overall, with low risk of hospital admission or death; about 40% of the oldest adults, however, remained uninfected and at highest risk of a severe outcome. First infections among older adults may still contribute substantial burden from COVID-19, reinforcing the need to continue to prioritize this age group for vaccination and to consider them in health care system planning.

Urinary concentrations of polycyclic aromatic hydrocarbon metabolites and childhood obesity.

Objectives: Existing literature provides limited information on the association between childhood obesity and polycyclic aromatic hydrocarbons (PAHs), which are potentially obesogenic. We examined the association between urinary concentrations of PAH metabolites and obesity in the Korean pediatric population. Methods: We analyzed the data of 2286 children/adolescents aged 3-17 years who participated in the Korean National Environmental Health Survey between 2015 and 2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography-mass spectrometry. Overweight/obesity was defined as a body mass index (BMI) for age ≥85th percentile. Multiple linear and logistic regression models were used to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAH metabolites after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and environmental tobacco smoke exposure. Results: BMI z-score was positively associated with 2-naphthol concentrations in children aged 6-11 and 12-17 years and with 1-hydroxypyrene concentrations in children aged 6-11 years. In the overall population, a significant rise in odds ratios for overweight/obesity across 2-naphthol quartiles was noted. Specifically, the 3rd and 4th quartiles displayed odds ratios of 1.39 [1.03, 1.88] and 1.46 [1.08, 1.99] respectively, compared to the 1st quartile (P-for-trend = 0.006). Similar associations between 2-naphthol and overweight/obesity status were observed in the 6-11- and 12-17-year age groups. There was little evidence of an association between overweight/obesity and other PAH hydroxy derivatives. Conclusions: PAH exposure may be associated with increased childhood adiposity, a potential risk factor for adult obesity and adverse metabolic outcomes.

Inhibition of Osteoclast Differentiation and Promotion of Osteogenic Formation by Wolfiporia extensa Mycelium.

Osteoporosis, Greek for "porous bone," is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as "Bokryung" in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.

Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020.

BACKGROUND: Over the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data. METHOD: The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study. RESULTS: A total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively. CONCLUSION: Based on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.

Vaccine effectiveness estimates from an early-season influenza A(H3N2) epidemic, including unique genetic diversity with reassortment, Canada, 2022/23.

The Canadian Sentinel Practitioner Surveillance Network estimated vaccine effectiveness (VE) during the unusually early 2022/23 influenza A(H3N2) epidemic. Like vaccine, circulating viruses were clade 3C.2a1b.2a.2, but with genetic diversity affecting haemagglutinin positions 135 and 156, and reassortment such that H156 viruses acquired neuraminidase from clade 3C.2a1b.1a. Vaccine provided substantial protection with A(H3N2) VE of 54% (95% CI: 38 to 66) overall. VE was similar against H156 and vaccine-like S156 viruses, but with potential variation based on diversity at position 135.

BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12-17 Years, by Dosing Interval and Duration.

BACKGROUND: Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. METHODS: Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. RESULTS: The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart. CONCLUSIONS: In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.

Differential alterations in brain structural network organization during addiction between adolescents and adults.

BACKGROUND: The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear. METHODS: Using independent component (IC) analysis on structural magnetic resonance imaging data, spatially ICs described as morphometric networks were extracted to examine the effects of MA use on gray matter (GM) volumes and network module connectivity in adolescents (51 MA users v. 60 controls) and adults (54 MA users v. 60 controls). RESULTS: MA use was related to significant GM volume reductions in the default mode, cognitive control, salience, limbic, sensory and visual network modules in adolescents. GM volumes were also reduced in the limbic and visual network modules of the adult MA group as compared to the adult control group. Differential patterns of structural connectivity between the basal ganglia (BG) and network modules were found between the adolescent and adult MA groups. Specifically, adult MA users exhibited significantly reduced connectivity of the BG with the default network modules compared to control adults, while adolescent MA users, despite the greater extent of network GM volume reductions, did not show alterations in network connectivity relative to control adolescents. CONCLUSIONS: Our findings suggest the potential of compensatory network reorganization in adolescent brains in response to MA use. The developmental characteristic to compensate for MA-induced brain damage can be considered as an age-specific therapeutic target for adolescent MA users.

Serial cross-sectional estimation of vaccine-and infection-induced SARS-CoV-2 seroprevalence in British Columbia, Canada.

BACKGROUND: The evolving proportion of the population considered immunologically naive versus primed for more efficient immune memory response to SARS-CoV-2 has implications for risk assessment. We sought to chronicle vaccine- and infection-induced seroprevalence across the first 7 waves of the COVID-19 pandemic in British Columbia, Canada. METHODS: During 8 cross-sectional serosurveys conducted between March 2020 and August 2022, we obtained anonymized residual sera from children and adults who attended an outpatient laboratory network in the Lower Mainland (Greater Vancouver and Fraser Valley). We used at least 3 immunoassays per serosurvey to detect SARS-CoV-2 spike and nucleocapsid antibodies. We assessed any seroprevalence (vaccineor infection-induced, or both), defined by positivity on any 2 assays, and infection-induced seroprevalence, also defined by dual-assay positivity but requiring both antinucleocapsid and antispike detection. We used estimates of infection-induced seroprevalence to explore underascertainment of infections by surveillance case reports. RESULTS: By January 2021, we estimated that any seroprevalence remained less than 5%, increasing with vaccine rollout to 56% by May-June 2021, 83% by September-October 2021 and 95% by March 2022. Infection-induced seroprevalence remained less than 15% through September-October 2021, increasing across Omicron waves to 42% by March 2022 and 61% by July-August 2022. By August 2022, 70%-80% of children younger than 20 years and 60%-70% of adults aged 20-59 years had been infected, but fewer than half of adults aged 60 years and older had been infected. Compared with estimates of infection-induced seroprevalence, surveillance case reports underestimated infections 12-fold between September 2021 and March 2022 and 92-fold between March 2022 and August 2022. INTERPRETATION: By August 2022, most children and adults younger than 60 years had evidence of both SARS-CoV-2 vaccination and infection. As previous evidence suggests that a history of both exposures may induce stronger, more durable hybrid immunity than either exposure alone, older adults - who have the lowest infection rates but highest risk of severe outcomes - continue to warrant prioritized vaccination.

Distribution and Function of Platelet-derived Growth Factor Receptor Alpha-positive Cells and Purinergic Neurotransmission in the Human Colon: Is It Different Between the Right and Left Colon?

Background/Aims: Platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells function in the purinergic regulation of gastrointestinal motility, and purines are reportedly inhibitory neurotransmitters in the enteric nervous system. We explore the distribution and function of PDGFRα+ cells related to purinergic inhibitory neurotransmission in human right and left colons. Methods: Human colonic segments were prepared with mucosa and submucosa intact, and the circular muscle tension and longitudinal muscle tension were recorded. Purinergic neurotransmitters were administered after recording the regular contractions. Immunohistochemistry was performed on the circular muscle layers. Intracellular recording was performed on the colonic muscular layer. SK3, P2RY1, and PDGFR-α mRNA expression was tested by quantitative real-time polymerase chain reaction (qPCR). Results: Adenosine triphosphate (ATP) treatment significantly decreased the frequency and area under the curve (AUC) of the segmental contraction in right and left colons. Beta-nicotinamide adenine dinucleotide (ß-NAD) decreased the frequency in the right colon and the amplitude, frequency and AUC in the left colon. Apamin significantly increased frequency and AUC in the left colon, and after apamin pretreatment, ATP and ß-NAD did not change segmental contractility. Through intracellular recordings, a resting membrane potential decrease occurred after ATP administration; however, the degree of decrease between the right and left colon was not different. PDGFRα+ cells were distributed evenly in the circular muscle layers of right and left colons. SK3, P2RY1, and PDGFRα expression was not different between the right and left colon. Conclusion: Purines reduce right and left colon contractility similarly, and purinergic inhibitory neurotransmission can be regulated by PDGFRα+ cells in the human colon.

Oat Seedlings Extract Inhibits RANKL-Induced c-Fos/NFATc1 Transcription Factors in the Early Stage of Osteoclast Differentiation.

Osteoporosis is a common disease that increases the risk of fractures due to decreased bone density and weakens the bone microstructure. Preventing and diagnosing osteoporosis using the available drugs can be a costly affair with possible side effects. Therefore, natural product-derived therapeutics are promising alternatives. Our study demonstrated that the oat seedlings' extract (OSE) inhibited the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis from the bone marrow-derived macrophages (BMMs). The OSE treatment significantly attenuated the RANKL-mediated induction of the tartrate-resistant acid phosphatase (TRAP) activity as well as the number of TRAP-positive (TRAP+) multinucleated cells (MNCs) counted through the TRAP staining in a dose-dependent manner. It was also confirmed that the OSE suppressed the formation of the TRAP + MNCs in the early stage of differentiation and not in the middle and late stages. The results of the real-time quantitative polymerase chain reaction (qPCR) and the western blotting showed that the OSE dramatically inhibited the mRNA and protein expressions of the osteoclastogenesis-mediated transcription factors such as the c-Fos and the nuclear factor-activated T cells c1 (NFATc1). In addition, the OSE strongly attenuated the mRNA induction of the c-Fos/NFATc1-dependent molecules such as the TRAP, the osteoclast-associatedimmunoglobulin-like receptor (OSCAR), the dendritic cell-specific transmembrane protein (DC-STAMP), and the cathepsin K. These results suggest that the naturally derived OSE may be useful for preventing bone diseases.

Influenza vaccine effectiveness against A(H3N2) during the delayed 2021/22 epidemic in Canada.

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: -38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization's decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.

Comparison between the International Classification of Primary Care and the International Classification of Diseases Classifications in Primary Care in Korea.

BACKGROUND: The International Classification of Primary Care-2 (ICPC-2) is a classification method designed for primary care. Although previous studies have found that ICPC-2 is a useful tool for demonstrating the relationship between patients' expectations and health providers' diagnoses, its utility of ICPC-2 has yet to be fully studied in Korea. This study aimed to evaluate the practicality of ICPC-2 in Korean primary care. METHODS: The study was conducted at primary care clinics in Seoul and Gyeonggi areas from October to November 2015. Third-year family medicine residents examined and analyzed the medical records of patients who visited primary care physicians using ICPC-2, and the results were compared with those obtained using the International Classification of Diseases-10 (ICD-10) (Korean version: Korean Standard Classification of Diseases-7). RESULTS: A total of 26 primary care physicians from 23 primary care clinics participated in the study. Furthermore, 2,458 ICD-10 codes and 6,091 ICPC-2 codes were recorded from the data of 1,099 patients. The common disease codes were vasomotor and allergic rhinitis (J30), according to ICD-10, and acute upper respiratory infection (R74) in ICPC-2. Comparing disease status by body systems, the proportion of gastrointestinal disease with ICD-10 codes was significantly higher than that with ICPC-2 codes (P<0.001). Furthermore, patients with >4 diagnoses accounted for 36% of the ICD-10 classifications, whereas those with >4 diagnoses accounted for 4% of the ICPC-2 classifications. CONCLUSION: Introducing ICPC as a complementary means for diagnosing common diseases could be a practical approach in Korean primary care.

Changes in lifestyle and obesity during the COVID-19 pandemic in Korean adolescents: based on the Korea Youth Risk Behavior Survey 2019 and 2020.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has affected people's daily lives and increased their time spent at home. This study aims to investigate the changes in lifestyle factors and obesity among Korean adolescents before and during the COVID-19 outbreak. METHODS: We used the data of 109,282 adolescents aged 12-18 years, from the Korea Youth Risk Behavior Survey conducted in 2019 and 2020 before and during the COVID-19 pandemic, respectively. The changes in the prevalence of obesity and lifestyle factors (diet, exercise, sitting time, and sleep duration) were assessed. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of predictors for obesity were calculated. RESULTS: The prevalence of overweight (10% to 10.5%) and obesity (11.5% to 12.7%) increased significantly, especially among males younger than 15 years, whereas significant differences were absent among females. The mean body mass index z-score increased from 0.28 to 0.39 in males but decreased from 0.08 to 0.04 in females. Fruit consumption, regular exercise, and average sleep duration decreased, whereas sitting time increased. After controlling for covariates, a short sleep duration (OR, 1.14) and an increased sitting time (OR, 1.14) were significantly associated with an elevated risk for overweight/obesity. CONCLUSION: During the COVID-19 pandemic, the prevalence of obesity and overweight increased, particularly in males, as did unfavorable trends in related lifestyle factors. Sex- and age-specific strategies to improve lifestyle factors associated with obesity are needed, especially during the COVID-19 pandemic.

Perilla frutescens Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation.

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether Perilla frutescens leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.

SARS-CoV-2 mRNA Vaccine Effectiveness in Health Care Workers by Dosing Interval and Time Since Vaccination: Test-Negative Design, British Columbia, Canada.

Background: One- and two-dose mRNA vaccine effectiveness (VE) estimates against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by dosing interval and time since vaccination were assessed among healthcare workers (HCWs) in publicly funded acute and community (nonresidential) healthcare facilities in British Columbia, Canada. Methods: A test-negative design was used with controls matched to cases (6:1) on epidemiological week of SARS-CoV-2 test date. mRNA vaccination was defined by receipt of the first dose ≥21 days or second dose ≥14 days before the test date. HCWs ≥18 years old tested for SARS-CoV-2 between epi-weeks 3 and 39 (January 17-October 2, 2021) were included, when varying dosing intervals and a mix of circulating variants of concern contributed, including Delta dominance provincially from epi-week 31 (August 1). Results: Single- and two-dose analyses included 1265 and 1246 cases, respectively. The median follow-up period (interquartile range) was 49 (34-69) days for single-dose and 89 (61-123) days for two-dose recipients, with 12%, 31%, and 58% of second doses given 3-5, 6, or ≥7 weeks after the first. Adjusted mRNA VE against SARS-CoV-2 was 71% (95% CI, 66%-76%) for one dose and 90% (95% CI, 88%-92%) for two doses, similar to two heterologous mRNA doses (92%; 95% CI, 86%-95%). Two-dose VE remained >80% at ≥28 weeks post-second dose. Two-dose VE was consistently 5%-7% higher with a ≥7-week vs 3-5-week interval between doses, but with overlapping confidence intervals. Conclusions: Among HCWs, we report substantial single-dose and strong and sustained two-dose mRNA vaccine protection, with the latter maintained for at least 7 months. These findings support a longer interval between doses, with global health and equity implications.