Different associations of specific non-alcoholic beverages with elevated high-sensitivity C-reactive protein in Korean adults: results from the Korea National Health and Nutrition Examination Survey (2015–2016)

This study examined the associations between specific non-alcoholic beverages and high-sensitivity C-reactive protein (hs-CRP) and their interactions with obesity. The study participants were 4,999 adults aged 19–64 years from the 2015–2016 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable logistic regression analyses. In women, there was an inverse linear trend between coffee and hs-CRP status (p_trend = 0.0137), and a positive linear trend for soda was also found (≥1/week vs never or almost never, OR = 1.79, 95% CI 1.23–2.61, p_trend = 0.0127). In the stratification analyses, the associa­tions were only observed in obese women. The associations were inverse for coffee and tea but linearly positive for soda in obese women (p_trend<0.05). In men, an inverted J-shaped association between commercial fruit juice/drink and hs-CRP status was found; but after stratification by obesity, the association was linear only in obese men (p_trend<0.05, OR = 2.44, 95% CI 1.44–4.16 in ≥1/week vs never or almost never). Coffee and tea in women may be beneficially associated with hs-CRP status, but soda in women and commercial fruit juice/drink in men may be adversely, particularly for obese adults.     

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer’s disease mice

Alzheimer’s disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disease with underlying pathologies that extend well beyond the widely recognized accumulation of amyloid beta (Aβ). Many studies have demonstrated that memory impairment in AD is driven by the interaction of various pathologic processes, such as cell death (1), impaired synapse plasticity (2), neurogenesis loss (3), autophagy dysfunction (4), vascular abnormalities (5), blood–brain barrier (BBB) damage (6), and systemic inflammation (7). Thus, effective drug development for this disorder must focus on therapeutic strategies that target the complex and multiple neuropathological features in AD.We and others have previously reported that the activity of several sphingolipid-metabolizing enzymes, especially acid sphingomyelinase (ASM), which is encoded by the SMPD1 gene, is abnormally expressed in AD patients and mouse models (8–10). The primary role of ASM is to catalyze the conversion of sphingomyelin, a major component of membranes, into ceramide and phosphocholine (11). The increased ASM activity in the blood and brain of AD mice contributes to various pathological features, including cell apoptosis (12), defective autophagy (8), neurogenesis loss (13), BBB leakage (14), and inflammation (15, 16), suggesting that ASM inhibition could be an important therapeutic target that addresses the neuropathological features of AD (17). Although some studies have previously identified direct or indirect functional inhibitors (17–20) of ASM, these inhibitors have lacked specificity, leading to the potential for off-target effects and unclear potential mechanisms of action in AD. Therefore, there is an important need to develop new compounds that block ASM activity by direct interaction with the enzyme.Here, we identify KARI 201 as a direct, selective, and competitive ASM inhibitor with excellent brain distribution and druggability. Interestingly, we also found an unexpected role of KARI 201 as an agonist of growth hormone secretagogue receptor 1α (GHSR1α, also known as the ghrelin receptor) via GPCR (G protein–coupled receptor) screening based on RNA-sequencing (RNA-seq) analysis in KARI 201–treated AD mice. This activity is critical for hippocampal synaptic physiology and may impact neuropathological features in AD as well (21–23). The dual action in neurons of KARI 201 as a direct ASM inhibitor and GHSR1α agonist led to outstanding, synergetic therapeutic effects in AD mouse models on neuropathological features involving learning and memory impairment. Therefore, our data highlight the possibility of clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.     

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity

BackgroundAtopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea.MethodsAD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups.ResultsA total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group.ConclusionThis study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.     

Usefulness of Bone SPECT/CT for Predicting Avascular Necrosis of the Femoral Head in Children with Slipped Capital Femoral Epiphysis or Femoral Neck Fracture

ObjectiveThis study aimed to investigate the usefulness of bone single-positron emission tomography/computed tomography (SPECT/CT) of the hip in predicting the later occurrence of avascular necrosis (AVN) after slipped capital femoral epiphysis (SCFE) or femoral neck fracture in pediatric patients. The quantitative parameters of SPECT/CT useful in predicting AVN were identified.Materials and MethodsTwenty-one (male:female, 10:11) consecutive patients aged < 18 years (mean age ± standard deviation [SD], 11.0 ± 2.7 years) who underwent surgery for SCFE or femoral neck fracture and postoperative bone SPECT/CT were included. The maximum standardized uptake value (SUV), mean SUV, and minimum SUV of the femoral head were measured. The ratios of the maximum SUV, mean SUV, and minimum SUV of the affected femoral head to the contralateral side were determined. Patients were followed up for > 1 year after the surgery. The SPECT/CT parameters were compared between patients who developed AVN and those who did not. The accuracy of SPECT/CT parameters for predicting AVN was assessed.ResultsSix patients developed AVN. There was a significant difference in the ratio of the mean SUV among patients who developed AVN (mean ± SD, 0.8 ± 0.3) and those who did not (1.1 ± 0.2, p = 0.018). However, there were no significant differences in the ratios of the maximum and minimum SUV between the groups (all p = 0.205). For the maximum, mean, and minimum SUVs, no significant differences were observed between the groups (p = 0.519, 0.733, and 0.470, respectively). The cutoff mean SUV ratio of 0.87 yielded a 66.7% sensitivity and 93.2% specificity for predicting AVN.ConclusionQuantitative bone SPECT/CT is useful for evaluating femoral head viability in pediatric patients with SCFE or femoral neck fractures. Clinicians should consider the high possibility of later AVN development in patients with a decreased mean SUV ratio.     

Comparison of Clinical and Radiologic Findings Between Perforated and Non-Perforated Choledochal Cysts in Children

ObjectiveTo compare the clinical and radiologic findings between perforated and non-perforated choledochal cysts in children.Materials and MethodsFourteen patients (mean age ± standard deviation, 1.7 ± 1.2 years) with perforated choledochal cysts (perforated group) and 204 patients (3.6 ± 3.8 years) with non-perforated choledochal cysts (non-perforated group) were included between 2000 and 2019. All patients underwent choledochal cyst excision after ultrasound, CT, or MR cholangiopancreatography. Relevant data including demographics, clinical symptoms, laboratory findings, imaging findings, and outcomes were analyzed. Statistical differences were compared using the Mann-Whitney U test and Fisher’s exact test.ResultsCholedochal cyst perforation occurred only in children under the age of 4 years. Acute symptoms, including fever (p < 0.001), were more common in the perforated group than in the non-perforated group. High levels of white blood cells (p = 0.004), C-reactive protein (p < 0.001), and serum amylase (p = 0.002), and low levels of albumin (p < 0.001) were significantly associated with the perforated group. All 14 patients with perforated choledochal cysts had ascites, whereas only 16% (33/204) of patients in the non-perforated group had ascites (p < 0.001). In the subgroup of patients who had ascites, a large amount of ascites (p = 0.001), increase in the amount of ascites in a short time (p < 0.001), complex ascites (p < 0.001), and perihepatic pseudocysts (p < 0.001) were more common in the perforated group than in the non-perforated group.ConclusionChildren with perforated choledochal cysts have characteristic clinical and radiologic findings compared to those with non-perforated choledochal cysts. In young children with choledochal cysts, perforation should be differentiated in cases with acute symptoms, laboratory abnormalities, and characteristic ascites findings.     

Impact of Skeletal Muscle Loss and Visceral Obesity Measured Using Serial CT on the Prognosis of Operable Breast Cancers in Asian Patients

ObjectiveThis study aimed to investigate the impact of baseline values and temporal changes in body composition parameters, including skeletal muscle index (SMI) and visceral adipose tissue area (VAT), measured using serial computed tomography (CT) imaging on the prognosis of operable breast cancers in Asian patients.Materials and MethodsThis study retrospectively included 627 Asian female (mean age ± standard deviation [SD], 53.6 ± 8.3 years) who underwent surgery for stage I–III breast cancer between January 2011 and September 2012. Body composition parameters, including SMI and VAT, were semi-automatically calculated on baseline abdominal CT at the time of diagnosis and follow-up CT for post-treatment surveillance. Serial changes in SMI and VAT were calculated as the delta values. Multivariable Cox regression analysis was used to evaluate the association of baseline and delta SMI and VAT values with disease-free survival.ResultsAmong 627 patients, 56 patients (9.2%) had breast cancer recurrence after a median of 40.5 months. The mean value ± SD of the baseline SMI and baseline VAT were 43.7 ± 5.8 cm²/m² and 72.0 ± 46.0 cm², respectively. The mean value of the delta SMI was -0.9 cm²/m² and the delta VAT was 0.5 cm². The baseline SMI and VAT were not significantly associated with disease-free survival (adjusted hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.937–1.031; p = 0.475 and adjusted HR, 1.001; 95% CI, 0.995–1.006; p = 0.751, respectively). The delta SMI and VAT were also not significantly associated with disease-free survival (adjusted HR, 0.894; 95% CI, 0.766–1.043; p = 0.155 and adjusted HR, 1.001; 95% CI, 0.989–1.014; p = 0.848, respectively).ConclusionOur study revealed that baseline and early temporal changes in SMI and VAT were not independent prognostic factors regarding disease-free survival in Asian patients undergoing surgery for breast cancer.     

Integrated Machine Vision System for Evaluating Hole Expansion Ratio of Advanced High-Strength Steels

In this paper, we propose a new method to estimate the hole expansion ratio (HER) using an integrated analysis system. To precisely measure the HER, three kinds of analysis methods (computer vision, punch load, and acoustic emission) were utilized to detect edge cracks during a hole expansion test. Cracks can be recognized by employing both computer vision and a punch load analysis system to determine the moment of crack initiation. However, the acoustic emission analysis system has difficulty detecting the instant of crack appearance since the magnitude of the audio signal is drowned out by noise from the press, which interrupts the differentiation of crack configuration. To enhance the accuracy for determining the HER, an integrated analysis system that combines computer vision with punch load analysis, and improves on the shortcomings of each analysis system, is newly suggested.     

Dual Pallidal and Thalamic Deep Brain Stimulation for Complex Ipsilateral Dystonia

PurposeGlobus pallidus pars interna (GPi) has become an established target for deep brain stimulation (DBS) in dystonia. Previous studies suggest that targeting the ventralis oralis (Vo) complex nucleus improves dystonic tremor or even focal dystonia. Research has also demonstrated that multi-target DBS shows some benefits over single target DBS. In this study, we reviewed patients who had undergone unilateral DBS targeting the GPi and Vo.Materials and MethodsFive patients diagnosed with medically refractory upper extremity dystonia (focal or segmental) underwent DBS. Two DBS electrodes each were inserted unilaterally targeting the ipsilateral GPi and Vo. Clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Disability Rating Scale.ResultsBFMDRS scores decreased by 55% at 1-month, 56% at 3-month, 59% at 6-month, and 64% at 12-month follow up. Disability Rating Scale scores decreased 41% at 1-month, 47% at 3-month, 50% at 6-month, and 60% at 12-month follow up. At 1 month after surgery, stimulating both targets improved clinical scores better than targeting GPi or Vo alone.ConclusionUnilateral thalamic and pallidal dual electrode DBS may be as effective or even superior to DBS of a single target for dystonia. Although the number of patients was small, our results reflected favorable clinical outcomes.     

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30–40 years, who were randomly assigned to two groups—a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.     

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.