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Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects.

Postural dysfunction is one of the most common community health symptoms and frequent chief complaints in hospitals. Sarcopenia is a syndrome characterized by degenerative loss of skeletal muscle mass, muscle quality, and muscle strength, and is the main contributor to musculoskeletal impairment in the elderly. Previous studies reported that loss of muscle mass is associated with a loss of diverse functional abilities. Meanwhile, there have been limited studies concerning postural dysfunction among older adults with sarcopenia. Although sarcopenia is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Also, recent studies recognize that sarcopenia may begin to develop earlier in life. The objective of this paper was to investigate the association between the prevalence of sarcopenia and postural dysfunction in a wide age range of adults using data from a nationally representative cohort study in Korea. Korean National Health & Nutrition Exhibition Survey V (KNHANES V, 2010-2012) data from the fifth cross-sectional survey of the South Korean population performed by the Korean Ministry of Health and Welfare were used. Appendicular skeletal muscle mass (ASM)/height (ht)2 was used to define sarcopenia, and the Modified Romberg test using a foam pad ("foam balance test") was performed to evaluate postural dysfunction. ASM/ht2 was lower in women and significantly decreased with age in men. Subjects with sarcopenia were significantly more likely to fail the foam balance test, regardless of sex and age. Regression analysis showed a significant relationship between sarcopenia and postural dysfunction (OR: 2.544, 95% CI: 1.683-3.846, p

Objectives Local administration of 3-nitropropionic acid (3-NP) to the inner ear induces sensorineural hearing loss. Several studies have shown the otoprotective effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether EGb 761 prevents 3-NP-induced sensorineural hearing loss and determine its effects on the expression of SIRT1. Methods Sprague Dawley rats were divided into four experimental groups: control group receiving vehicle of 3-NP, EGb group receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb 761 and 3-NP. EGb 761 was given orally for 5 days. The 3-NP solution was injected into the tympanum 3 days after the start of EGb 761 administration. The auditory brainstem response was recorded before and after the injection. At 4 weeks after the administration of 3-NP or vehicle of 3-NP, cochleae were harvested, and hematoxylin and eosin staining and immunohistochemistry for SIRT1 antibody were performed. Results EGb+3-NP group showed significantly lower threshold shifts than 3-NP group. There was a significant preservation of type II fibrocytes and spiral ganglion cells in EGb+3-NP group than in 3-NP group. In EGb+3-NP group, there was a significantly greater number of SIRT1 immunopositive type II fibrocytes and spiral ganglion cells than in 3-NP group. Calculating the percentage of SIRT1 immunoreactive type II fibrocytes and spiral ganglion cells in viable type II fibrocytes and spiral ganglion cells, respectively, EGb+3-NP group showed significantly higher SIRT1 immunoreactive cells than 3-NP group. Conclusion These results suggest that EGb 761 may prevent hearing loss induced by 3-NP in an acute ototoxic animal model, which appears to be related with SIRT1 expression.

Sensorineural hearing loss (SNHL) is a multifactorial disease that more frequently affects preterm newborns. Although a number of maternal conditions have been reported to be associated with preterm birth, little information is available concerning maternal risk factors for the development of SNHL. We aimed to identify maternal and placental risk factors associated with a “refer” result on the newborn hearing screening (NHS) test and subsequently confirmed SNHL in very preterm neonates. Methods: This retrospective cohort study included 267 singleton neonates who were born alive after ≤ 32 weeks. Histopathologic examination of the placenta was performed, and clinical data were retrieved from a computerized perinatal database. Cases with two abnormal findings, “refer” on the NHS test, and presence of SNHL on the confirmation test were retrospectively reviewed based on electronic medical records. Results: Forty-two neonates (15.7%) showed a “refer” result, and, on the confirmation test, permanent SNHL was identified in 1.87% (5/267) of all neonates. Multivariate regression analysis revealed that the presence of funisitis was independently associated with a “refer” on the NHS test, whereas use of antenatal corticosteroids was statistically significantly associated with a reduced incidence of “refer” on the screening test. Neither histologic chorioamnionitis nor prematurity (as defined by low gestational age and birth weight) was associated with a “refer” on the NHS test. By contrast, multivariate analysis with occurrence of SNHL as a dependent variable identified no significant associations with the parameters studied, probably owing to the small total number of neonates with permanent SNHL. Conclusion: Presence of funisitis was significantly and independently associated with increased risk of abnormal NHS results, while administration of antenatal corticosteroids was related to a normal NHS result. These findings support the hypothesis that a systemic fetal inflammatory response, manifested as funisitis, might play a role in the pathogenesis of SNHL in preterm neonates.

Off-vertical axis rotation (OVAR) is a laboratory test to assess the otolith function. This study aimed to analyze the parameters of OVAR in patients with unilateral vestibular hypofunction (UVH) and bilateral vestibulopathy (BVP), and to correlate the parameters of OVAR with those of VEMPs. Ten healthy volunteers, 41 UVH, and 13 BVP patients performed OVAR. Bias component (BIC) and modulation component (MOC) of UVH and BVP patients were compared with those of healthy controls. BIC and MOC were correlated with amplitude and interaural difference (IAD) of cervical VEMP (cVEMP) and ocular VEMP (oVEMP). In UVH patients, the direction of BICs to affected side rotation were reversed and the absolute value of BICs were decreased when they were compared to healthy controls. In BVP patients, BICs were markedly attenuated. MOCs were not changed in UVH and BVP patients. There was no statistically significant correlation between VEMPs and OVAR.

The cell-penetrating peptide GV1001 has been investigated as an anticancer agent and recently demonstrated anti-oxidant and anti-inflammatory effects. It has shown a protective effect on a kanamycin (KM)-induced ototoxicity mouse model. In the present study, we administered GV1001 at different time points after inducing hair cell damage, and examined if it rescues hair cell loss and restores hearing. A deaf mouse model was created by intraperitoneal injection of KM and furosemide. First, to test the early temporal change of hearing and extent of hair cell damage after KM and furosemide injection, hearing and outer hair cells (OHCs) morphology were evaluated on day 1, day 2 and day 3 after injection. In the second experiment, following KM and furosemide injection, GV1001, dexamethasone, or saline were given for three consecutive days at different time points: D0 group (days 0, 1, and 2), D1 group (days 1, 2, and 3), D3 group (days 3, 4, and 5) and D7 group (days 7, 8, and 9). The hearing thresholds were measured at 8, 16, and 32 kHz before ototoxic insult, and 7 days and 14 days after KM and furosemide injection. After 14 days, each turn of the cochlea was imaged to evaluate OHCs damage. GV1001-treated mice showed significantly less hearing loss and OHCs damage than the saline control group in the D0, D1 and D3 groups (p < 0.0167). However, there was no hearing restoration or intact hair cell in the D7 group. GV1001 protected against cochlear hair cell damage, and furthermore, delayed administration of GV1001 up to 3 days rescued hair cell damage and hearing loss in KM/furosemide-induced deaf mouse model.

Background:Streptococcus pneumoniae colonize the human nasopharynx in the form of biofilms. The biofilms act as bacterial reservoirs and planktonic bacteria from these biofilms can migrate to other sterile anatomical sites to cause pneumonia, otitis media (OM), bacteremia and meningitis. Human amniotic membrane contains numerous growth factors and antimicrobial activity; however, these have not been studied in detail. In this study, we prepared amniotic membrane extract and chorionic membrane extract (AME/CME) and evaluated their antibacterial and antibiofilm activities against S. pneumoniae using an in vitro biofilm model and in vivo OM rat model.Materials and Methods: The AME/CME were prepared and protein was quantified using DCTM (detergent compatible) method. The minimum inhibitory concentrations were determined using broth dilution method, and the synergistic effect of AME/CME with Penicillin-streptomycin was detected checkerboard. The in vitro biofilm and in vivo colonization of S. pneumoniae were studied using microtiter plate assay and OM rat model, respectively. The AME/CME-treated biofilms were examined using scanning electron microscope and confocal microscopy. To examine the constituents of AME/CME, we determined the proteins and peptides of AME/CME using tandem mass tag-based quantitative mass spectrometry.Results: AME/CME treatment significantly (p < 0.05) inhibited S. pneumoniae growth in planktonic form and in biofilms. Combined application of AME/CME and Penicillin-streptomycin solution had a synergistic effect against S. pneumoniae. Biofilms grown with AME/CME were thin, scattered, and unorganized. AME/CME effectively eradicated pre-established pneumococci biofilms and has a bactericidal effect. AME treatment significantly (p < 0.05) reduced bacterial colonization in the rat middle ear. The proteomics analysis revealed that the AME/CME contains hydrolase, ribonuclease, protease, and other antimicrobial proteins and peptides.Conclusion: AME/CME inhibits S. pneumoniae growth in the planktonic and biofilm states via its antimicrobial proteins and peptides. AME/CME are non-cytotoxic, natural human product; therefore, they may be used alone or with antibiotics to treat S. pneumoniae infections.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronically progressive or relapsing symmetric sensorimotor disorder presumed to occur because of immunologic antibody-mediated reactions. To understand the clinical courses of CIDP, we report variable CIDP courses in children with respect to initial presentation, responsiveness to medical treatment, and recurrence interval. Four patients who were diagnosed with acute-onset and relapsing CIDP courses at Severance Children's Hospital, Seoul, Korea, were enrolled in this retrospective study. We diagnosed each patient on the basis of the CIDP diagnostic criteria developed in 2010 by the European Federation of Neurological Societies/Peripheral Nerve Society Guidelines. We present the cases of four pediatric patients diagnosed with CIDP to understand the variable clinical course of the disease in children. Our four patients were all between 8 and 12 years of age. Patients 1 and 2 were diagnosed with acute cerebellar ataxia or Guillain-Barré syndrome as initial symptoms. While patients 1 and 4 were given only intravenous dexamethasone (0.3 mg/kg/day) for 5 days at the first episode, Patients 2 and 3 were given a combination of intravenous immunoglobulin (2 g/kg) and dexamethasone (0.3 mg/kg/day). All patients were maintained with oral prednisolone at 30 mg/day, but their clinical courses were variable in both relapse intervals and severity. We experienced variable clinical courses of CIDP in children with respect to initial presentation, responsiveness to medical treatment, and recurrence interval.

Phthalates are commonly used as plasticizers and vehicles for cosmetic ingredients. Phthalate metabolites have documented biochemical activity including activating peroxisome proliferator-activated receptor and antiandrogenic effects, which may contribute to the development of obesity. In vitro and in vivo studies suggest that phthalates have significant effects on the development of obesity, especially after prenatal exposure at low doses. Although few studies have examined the effects of phthalate on obesity development in humans, some work has shown that phthalates affect humans and animals similarly. In this paper, we review the possible mechanisms of phthalate-induced obesity, and discuss evidence supporting the role of phthalates in the development of obesity in humans.

We aimed to compare the diagnostic yield between temporal bone computed tomography (TBCT) and internal auditory canal MRI (IAC MRI) for the etiologic diagnosis of children with congenital single-sided deafness (SSD) and the evaluation of cochlear implant (CI) candidacy. In the original cohort, 24 subjects with congenital SSD were enrolled and underwent both TBCT and IAC MRI. We recruited an additional 22 consecutive infants with congenital SSD (the supplementary cohort) and evaluated in particular the cochlear nerve (CN) integrity using IAC MRI. Cochlear nerve deficiency (CND) was classified as ‘absent’, ‘small’, and ‘indeterminate’ via mutual comparison between optical and parameters based on the MRI results. The most common etiologies were CND in the original cohort (19 out of 24). Notably, accurate evaluations of CN status (‘small CN’ = 2, ‘indeterminate CN’ = 2), inner ear malformations, and brain abnormalities were possible only with MRI. The ‘indeterminate CN’ tended to be more frequently detected in SSD ears than in unaffected ears. MRI appeared to be more accurate than TBCT in a meticulous differentiation of CN, which is crucial for the selection of appropriate CI candidacy among congenital SSD children. Additionally, we introduced the novel concept of ‘indeterminate CN’, of which the causal relationship with SSD awaits confirmation.

Although vascular pulsatile tinnitus (VPT) has been classified as "objective", VPT is not easily recognizable or documentable in most cases. In response to this, we have developed transcanal sound recording (TSR) and spectro-temporal analysis (STA) for the objective diagnosis of VPT. By refining our initial method, we were able to apply TSR/STA to post-treatment outcome evaluation, as well as pre-treatment objective diagnosis.TSR was performed on seven VPT patients and five normal controls before and after surgical or interventional treatment. VPT was recorded using an inserted microphone with the subjects placed in both upright and supine positions with 1) a neutral head position, 2) head rotated to the tinnitus side, 3) head rotated to the non-tinnitus side, and 4) a neutral position with ipsi-lesional manual cervical compression. The recorded signals were analyzed in both time and time-frequency domains by performing a short-time Fourier transformation.The pre-treatment ear canal signals of all VPT patients demonstrated pulse-synchronous periodic structures and acoustic characteristics that were representative of their presumptive vascular pathologies, whereas those the controls exhibited smaller peaks and weak periodicities. Compared with the pre-treatment signals, the post-treatment signals exhibited significantly reduced peak- and root mean square amplitudes upon time domain analysis. Additionally, further sub-band analysis confirmed that the pulse-synchronous signal of all subjects was not identifiable after treatment and, in particular, that the signal decrement was statistically significant at low frequencies. Moreover, the post-treatment signals of the VPT subjects revealed no significant differences when compared to those of the control group.We reconfirmed that the TSR/STA method is an effective modality to objectify VPT. In addition, the potential role of the TSR/STA method in the objective evaluation of treatment outcomes in patients with VPT was proven. Further studies incorporating a larger sample size and more refined recording techniques are warranted.

Phytoestrogen is an estrogenic compound that occurs naturally in plants. The most common sources of phytoestrogen are soybean products, which contain high levels of isoflavones. This compound, which has structural similarity with estrogen, can act as an estrogen receptor agonist or antagonist. Animal studies provide evidence of the significant effects of phytoestrogen on sexual development, including altered pubertal timing, impaired estrous cycling and ovarian function, and altered hypothalamus and pituitary functions. Although human studies examining the effects of phytoestrogen on sexual development are extremely limited, the results of some studies agree with those of the animal studies. In this paper, we review the possible mechanism of phytoestrogen action and the evidence showing the effects of phytoestrogen on sexual development in animal and human studies.

PurposeRecombinant human growth hormone (rhGH) has been widely used to treat short stature. However, there are some concerns that growth hormone treatment may induce skeletal maturation and early onset of puberty. In this study, we investigated whether rhGH can directly affect the neuronal activities of of gonadotropin-releasing hormone (GnRH).MethodsWe performed brain slice gramicidin-perforated current clamp recording to examine the direct membrane effects of rhGH on GnRH neurons, and a whole-cell voltage-clamp recording to examine the effects of rhGH on spontaneous postsynaptic events and holding currents in immature (postnatal days 13-21) and adult (postnatal days 42-73) mice.ResultsIn immature mice, all 5 GnRH neurons recorded in gramicidin-perforated current clamp mode showed no membrane potential changes on application of rhGH (0.4, 1 µg/mL). In adult GnRH neurons, 7 (78%) of 9 neurons tested showed no response to rhGH (0.2-1 µg/mL) and 2 neurons showed slight depolarization. In 9 (90%) of 10 immature neurons tested, rhGH did not induce any membrane holding current changes or spontaneous postsynaptic currents (sPSCs). There was no change in sPSCs and holding current in 4 of 5 adult GnRH neurons.ConclusionThese findings demonstrate that rhGH does not directly affect the GnRH neuronal activities in our experimental model.

BACKGROUND:Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children. METHODS:Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs. RESULTS:The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (≥6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P

Abstract The occurrence of osteoporosis gradually increases within the aging population. As the side effects of therapeutic agents currently used for osteoporosis are increasing, the development of preventive and therapeutic agents derived from natural products without any long-term side effects is important. Here, we investigated the effect of wheat seedling extract (WSE) on the RANKL-mediated differentiation, fusion, and function of osteoclasts. WSE inhibited the differentiation of RANKL-induced bone marrow macrophages and phosphorylation of AKT and ERK. Moreover, the protein and mRNA expression levels of c-Fos and NFATc1 as well as RANKL-induced transcription of TRAP and OSCAR were suppressed by WSE treatment. DC-STAMP and cathepsin K, which are essential for cell fusion and bone degradation, were also inhibited by WSE. Furthermore, eight components constituting WSE were confirmed to decrease the osteoclast TRAP activity. Taken together, WSE may have potential implications as a useful therapeutic or preventive agent for inhibition of bone loss.

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.

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.

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.

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. Conclusions 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.

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.

Abstract Introduction: Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported. Objective: In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature. Methods: A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed. Results: Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded. Conclusion: Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended.

The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca2+ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate-induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons. [ABSTRACT FROM AUTHOR]