Unraveling the diagnostic odyssey: stimulator of interferon gene-associated vasculopathy with onset in infancy in a 30-year-old female.

Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female Korean patient with early-onset interstitial lung disease who was initially suspected to have systemic lupus erythematosus (SLE) but was ultimately diagnosed with SAVI. The patient exhibited signs of interstitial lung disease and cutaneous manifestations before the age of 1 year and continued to have recurrent fever accompanied by pulmonary infiltrates. Based on positive findings for antibodies associated with SLE, such as antinuclear antibodies and anti-double-stranded DNA, the pulmonary involvement was considered a manifestation of SLE. Another significant symptom was recurrent skin ulceration, which led to partial spontaneous amputation of most of the toes due to inflammation. Given the early onset of interstitial lung disease, severe skin ulcers, and symptoms resembling SLE, autoinflammatory syndrome, especially SAVI was suspected. Following confirmation by genetic testing at age 29 years, the patient was started on tofacitinib, a Janus kinase inhibitor. Despite the prolonged use of multiple immunosuppressive therapies, the patient's lung condition continued to worsen, ultimately requiring lung transplantation. This observational report highlights the importance of considering SAVI as a potential diagnosis when manifestations of interstitial lung disease are observed during infancy. Early proactive treatment is crucial for lung involvement, as this can have long-term effects on patient's prognosis.

Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis.

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Replacing Mercury Sphygmomanometers With Mercury-Free Sphygmomanometers for the National Health Survey in Children: Direct Comparisons Applying Two Types of Mercury-Free Sphygmomanometer.

BACKGROUND AND OBJECTIVES: Blood pressure (BP) measurement using an auscultatory sphygmomanometer is recommended for diagnosing hypertension in children. As mercury sphygmomanometers (MSs) are banned owing to environmental concerns, it is crucial to determine the accuracy of mercury-free sphygmomanometers to replace them. We analyzed the accuracy of these devices to guide the National Survey selection. METHODS: BP was measured thrice each with MS, auscultatory device (AD), and oscillometric device (OD) in 104 participants aged 10-18 using the National Survey data. The difference in BP was defined as the difference between MS and other devices. The BP differences, correlations, and influencing factors were analyzed. The frequencies of hypertension were also compared. RESULTS: Systolic BP (SBP) and diastolic BP (DBP) differences between MS and AD were 0.88±3.36 mmHg and 0.63±3.95 mmHg, and those between MS and OD were 0.43±5.83 mmHg and 4.57±6.89 mmHg, respectively. The absolute error of <10 mmHg for DBP between MS and OD was 76%. The concordance correlation coefficient between MS and AD was 0.94 for SBP and 0.90 for DBP, and 0.81 and 0.67, respectively for MS and OD. Arm circumference negatively correlated with BP differences except for SBP between the MS and OD. The frequency of hypertension was not different between MS and AD but was underestimated by OD. CONCLUSIONS: AD correlated well with MS, while OD did not, especially for DBP. The superiority of AD over OD suggests AD as a possible alternative for MS in the National Survey.

Comparisons of an automated oscillometric device with a hybrid manual auscultatory device for the Korea National Health and Nutrition Examination Survey.

This study evaluated an oscillometric device (OD), Microlife WatchBP Office AFIB, and a hybrid manual auscultatory device (AD), Greenlight 300TM, to determine a suitable blood pressure (BP) measurement device for the Korea National Health and Nutrition Examination Survey in a mercury-free context. Adhering to the 2018 Universal Standard's suggested consensus, the study involved 800 subjects (mean age 51.2 ± 17.5 years; 44.3% male), who underwent triplicate BP measurements following 5 min of rest in a randomized order (OD-first: 398 participants; AD-first: 402 participants). BP difference was calculated as OD value minus AD value, with results stratified by measurement sequence. The overall BP difference and tolerable error probability were -1.1 ± 6.5/-2.6 ± 4.9 mmHg and 89.2%/92.5% for systolic/diastolic BP (SBP/DBP), respectively. Lin's concordance correlation coefficient was 0.907/0.844 for SBP/DBP (OD-first/AD-first: 0.925/0.892 for SBP, 0.842/0.845 for DBP). The overall agreement for hypertension (BP ≥ 140 and/or 90 mmHg) was 0.71 (p < 0.0001), and the OD underestimated the overall hypertension prevalence by 5.1%. Analysis of the AD-first data revealed a lower level of agreement compared to the OD-first data; however, the observed blood pressure difference adhered to Criterion 1 of the 2018 Universal Standard. Microlife met the Criterion 1 of 2018 Universal Standard but underestimated the prevalence of hypertension. The BP discrepancy increased with higher BP levels, male sex, and smaller AC. With increasing age, the discrepancy decreased for SBP and increased for DBP.

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

Background: The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. Methods: We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. Results: In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). Conclusion: We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

Robust anion exchange membranes based on ionic liquid grafted chitosan/polyvinyl alcohol/quaternary ammonium functionalized silica for polymer electrolyte membrane fuel cells.

In this study, 1-bromohexyl-1methylpiperidinium bromide (Br-6-MPRD) ionic liquid grafted quaternized chitosan (QCS) and polyvinyl alcohol (PVA) blends were composited with glycidyl trimethyl ammonium chloride (GTMAC) quaternized silica (QSiO2) at different dosages. Glutaraldehyde (GA) crosslinked the membranes and then processed into hydroxide form with an aqueous potassium hydroxide solution. The resultant IL-QCS/PVA/QSiO2 membranes exhibit significantly improved ionic conductivity, moderate water absorption and swelling ratio compared with the pristine IL-QCS/PVA anion exchange membrane (AEM). Among them, the hydroxide ion conductivity and power density of IL-QCS/PVA/QSiO2-7 membrane can reach up to 78 mS cm-1 at 80 °C and 115 mW cm-2 at 60 °C respectively. In addition, IL-QCS/PVA/QSiO2 membranes have excellent thermal, mechanical, and chemical stabilities, which can meet the application requirements of AEM for fuel cells.

Clinical characteristics of juvenile systemic sclerosis in Korea: 31-year single-center study.

Objective: To evaluate the clinical and laboratory characteristics, therapeutic drugs, and prognosis of juvenile systemic sclerosis (JSSc) at a single center in Korea. Methods: This study was a retrospective analysis of patients with JSSc aged <16 years at disease onset and who were treated at our hospital between January 1992 and April 2023. All patients met the Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc, and those with localized scleroderma (morphea) were excluded. Results: Among the 13 patients, proximal skin sclerosis (100%), Raynaud's phenomenon (RP) (84.6%), and sclerodactyly (69.2%) were present at the time of diagnosis. The most common symptom before diagnosis was RP, which was present in 10 patients (76.9%), whereas proximal skin sclerosis was observed in only five patients (38.5%). Thirteen patients had positive anti-nuclear antibody (ANA). At the time of diagnosis, five individuals had findings suggestive of interstitial lung disease (ILD) on a pulmonary function test (PFT) or chest computed tomography (CT), two of whom were asymptomatic. During follow-up, three patients developed ILD, one developed renal dysfunction, one developed heart disease, and none died. Conclusion: This study was the first descriptive analysis of clinical features of JSSc in South Korea. Clinical suspicion is essential for diagnosing JSSc in patients with RP, especially if ANA is positive; however, proximal skin sclerosis, which is crucial for diagnosing JSSc, was unrecognized in the early phase of the disease. PFT should be considered even if a patient is asymptomatic or has normal chest CT.

Long-term outcomes and associated prognostic risk factors of childhood-onset lupus nephritis.

Background: This study investigated the clinical characteristics and kidney outcomes of childhood-onset lupus nephritis (LN), and risk factors associated with prognosis. Methods: We enrolled 216 patients with histologically diagnosed LN during childhood. The Korean Society of Pediatric Nephrology organized a retrospective cohort study of childhood-onset LN in 13 major pediatric nephrology centers in South Korea. Results: The mean age at kidney biopsy was 13.2 ± 3.22 years. The main forms of presentation were nephrotic syndrome and/or hematuria in 152 patients (70.4%), and the most common histological finding was World Health Organization (WHO) class IV in 138 patients (63.9%), followed by WHO class III in 34 patients (15.7%). In the outcome analysis, the mean follow-up period of the patients was 7.8 ± 5.11 years. At last follow-up, 32 patients (14.8%) developed advanced chronic kidney disease (CKD). Male sex and failure to achieve remission at 12 months of treatment were significant risk factors for developing advanced CKD (hazard ratio of 2.57 and 2.29, respectively). Conclusion: Our study demonstrated the clinical characteristics and long-term outcomes of patients with childhood-onset LN. Male sex and failure to achieve remission in the first year of treatment were predictive of advanced CKD. Therefore, prompt awareness and close monitoring of these high-risk patients are needed, which may further improve the prognosis of children with LN.

A selective ER-phagy exerts neuroprotective effects via modulation of α-synuclein clearance in parkinsonian models.

The endoplasmic reticulum (ER) is selectively degraded by ER-phagy to maintain cell homeostasis. α-synuclein accumulates in the ER, causing ER stress that contributes to neurodegeneration in Parkinson's disease (PD), but the role of ER-phagy in α-synuclein modulation is largely unknown. Here, we investigated the mechanisms by which ER-phagy selectively recognizes α-synuclein for degradation in the ER. We found that ER-phagy played an important role in the degradation of α-synuclein and recovery of ER function through interaction with FAM134B, where calnexin is required for the selective FAM134B-mediated α-synuclein clearance via ER-phagy. Overexpression of α-synuclein in the ER of the substantia nigra (SN) resulted in marked loss of dopaminergic neurons and motor deficits, mimicking PD characteristics. However, enhancement of ER-phagy using FAM134B overexpression in the SN exerted neuroprotective effects on dopaminergic neurons and recovered motor performance. These data suggest that ER-phagy represents a specific ER clearance mechanism for the degradation of α-synuclein.

Clinical course of post-kidney transplant Schimke immuno-osseous dysplasia.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare systemic disease characterized by short stature, proteinuria, and recurrent infections. Patients usually have spondyloepiphyseal dysplasia, and progressive steroid-resistant nephropathy that leads to kidney failure. However, their clinical course after kidney transplantation (KT) is not yet well known. Here, we present our experience with cases of SIOD treated at our institute. CASE PRESENTATION: Since 2014, three children have been diagnosed with nephropathy resulting from SIOD. They presented with proteinuria in the nephrotic range at 7, 5, and 3 years of age. Focal segmental glomerulosclerosis was confirmed and progressed to kidney failure approximately 2 years after proteinuria was detected. These patients underwent living-donor KT from their parents. After KT, Case 1 lost his graft within 7 months due to multi-organ failure caused by disseminated adenovirus infection and died. Case 2 experienced graft failure 5 years after KT due to acute rejection from poor compliance. In Case 3, the allograft was still functioning 6 years after KT with low-dose tacrolimus single medication (trough level < 5 ng/mL). Extra-renal manifestations progressed regardless of KT, namely, right renal vein thrombosis and pulmonary hypertension in Case 1, severe bilateral hip dysplasia and Moyamoya syndrome in Case 2, and neutropenia and thrombocytopenia in Case 3, in addition to recurrent infection. CONCLUSION: In SIOD patients, KT is complicated with recurrent infections due to their inherent immune dysfunction. Additionally, extra-renal symptoms may render the patients morbid despite the recovery of kidney function.

Corrigendum: Mineral bone disorder in children with chronic kidney disease: data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study.

[This corrects the article DOI: 10.3389/fped.2023.994979.].

Corrigendum: Long-term outcome of Bartter syndrome in 54 patients: a multicenter study in Korea.

[This corrects the article DOI: 10.3389/fmed.2023.1099840.].

Association between serum total cholesterol and chronic kidney disease progression in children: results from the KNOW-PedCKD.

BACKGROUND: Dyslipidemia can cause cardiovascular disease and increase the fatality rate among children with chronic kidney disease (CKD); this makes early screening and treatment of dyslipidemia crucial. This study aimed to assess the association between the changes in serum total cholesterol levels over time and the degree of CKD progression in children. METHODS: From April 2011 to August 2021, 379 of the 432 participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric CKD (KNOW-PedCKD) were included and divided into 4 categories based on total cholesterol levels (< 170 mg/dL, acceptable; 170-199, borderline; 200-239, high; and ≥ 240, very high). Survival analysis using conventional and time-dependent Cox proportional hazards model were performed for a composite event of CKD progression (≥ 50% decrease in estimated glomerular filtration rate from baseline, a twofold increase in creatinine, or the occurrence of dialysis or kidney transplantation). RESULT: The incidence of composite event of CKD progression was 96.3, 90.4, 87.3, and 270.6 cases per 1000 person-years in the acceptable, borderline, high, and very high categories, respectively. On using the time-dependent Cox proportional hazards model, the hazard ratio of the very high category was significantly higher than that of the acceptable category by 3.13 times as per univariate analysis and 2.37 times as per multivariate analysis. CONCLUSIONS: Very high serum total cholesterol is a significant risk factor for CKD progression in children. Lowering total cholesterol levels below the very high category in children with CKD may delay the progression of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study.

Background: Children with chronic kidney disease (CKD) are at high risk of mineral bone disorder (MBD), which leads to fractures, growth retardation, and cardiovascular disease. We aimed to comprehensively understand the relationship between renal function and factors related to MBD and evaluate the prevalence and distribution characteristics of MBD, specifically among Korean patients from the KNOW-PedCKD cohort. Methods: From the baseline data of the KNOW-PedCKD cohort, we examined the prevalence and distribution of MBD in 431 Korean pediatric CKD patients, including the level of corrected total calcium, serum phosphate, serum alkaline phosphatase, serum intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF-23), serum vitamin D, fractional excretion of phosphate (FEP), and bone densitometry Z-scores. Results: The median serum calcium level remained relatively normal regardless of the CKD stage. The levels of 1,25-dihydroxy vitamin D, urine calcium-to-creatinine ratio, and bone densitometry Z-score significantly decreased with advancing CKD stage, while those of serum phosphate, FGF-23, and FEP significantly increased with CKD stage. The prevalence of hyperphosphatemia (17.4%, 23.7%, and 41.2% from CKD stages 3b, 4, and 5, respectively) and hyperparathyroidism (37.3%, 57.4%, 55.3%, and 52.9% from CKD stages 3a, 3b, 4, and 5, respectively) significantly increased with the CKD stage. Prescriptions of medications, such as calcium supplements (39.1%, 42.1%, 82.4%), phosphate binders (39.1%, 43.4%, 82.4%), and active vitamin D (21.7%, 44.7%, and 64.7%) significantly increased with CKD stage 3b, 4, and 5, respectively. Conclusions: The results demonstrated the prevalence and relationship of abnormal mineral metabolism and bone growth according to CKD stage in Korean pediatric CKD patients for the first time.

Long-term outcome of Bartter syndrome in 54 patients: A multicenter study in Korea.

Introduction: Bartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce. Methods: We retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea. Results: All patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0-271) months, and their median follow-up was 8 (range, 0.5-27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had SLC12A1 gene mutations, 1 had KCNJ1 gene mutations, 33 had CLCNKB gene mutations, and 1 had BSND mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, n = 4; CKD G5, n = 2]. Conclusion: BS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3-G5.

Degradation phenomena of quantum dot light-emitting diodes induced by high electric field.

Quantum dots possess exceptional optoelectronic properties, such as narrow bandwidth, controllable wavelength, and compatibility with solution-based processing. However, for efficient and stable operation in electroluminescence mode, several issues require resolution. Particularly, as device dimensions decrease, a higher electric field may be applied through next-generation quantum dot light-emitting diode (QLED) devices, which could further degrade the device. In this study, we conduct a systematic analysis of the degradation phenomena of a QLED device induced by a high electric field, using scanning probe microscopy (SPM) and transmission electron microscopy (TEM). We apply a local high electric field to the surface of a QLED device using an atomic force microscopy (AFM) tip, and we investigate changes in morphology and work function in the Kelvin probe force microscopy mode. After the SPM experiments, we perform TEM measurements on the same degraded sample area affected by the electric field of the AFM tip. The results indicate that a QLED device could be mechanically degraded by a high electric field, and work function changes significantly in degraded areas. In addition, the TEM measurements reveal that In ions migrate from the indium tin oxide (ITO) bottom electrode to the top of the QLED device. The ITO bottom electrode also deforms significantly, which could induce work function variation. The systematic approach adopted in this study can provide a suitable methodology for investigating the degradation phenomena of various optoelectronic devices.

Changes in Awareness Toward Minor's Organ Donation Through Structured Information; Survey.

This study analyzed survey results regarding awareness of living minors' organ donation. The questionnaires focused on changes in how respondents felt about donations by living minors after eliciting the uncertainty of long-term outcomes for living donors and recipients. The respondents were categorized as minors, adults affiliated with non-medical jobs (Non-Meds), and adults affiliated with medical jobs (Meds). The rates of awareness of living organ donation were significantly different; minors at 86.2%, non-Meds at 82.0%, and Meds at 98.7% (p < 0.001). Only 41.4% of Minors and 32.0% of Non-Meds were aware of organ donation by minors, while 70.3% of Meds were (p < 0.001). The response rate of opposition to organ donation by minors was highest for Meds and remained the same before and after (54.4%-57.7%, p = 0.311). However, the opposition rate in Non-Meds significantly increased (32.4%-46.7%) after learning about the uncertainty of long-term outcomes (p = 0.009). The study found that Non-Meds lacked adequate knowledge regarding organ donation by minors and their potential lethal outcomes. Their attitudes toward organ donation by minors could be changed by giving structured information. It is necessary to provide exact information and raise social awareness regarding organ donation by living minors.

Effect of moderate to severe atopic dermatitis on the prognosis of egg allergy resolution

BACKGROUND: Few studies have examined the effect of atopic dermatitis (AD) on the resolution of food allergies in Asia, and the predictors of egg allergy resolution are not yet well defined. OBJECTIVE: We evaluated whether AD severity could predict the resolution of egg allergy. METHODS: This retrospective cohort study included infants under 24 months of age diagnosed with IgE-mediated egg white allergy. We included subjects who completed a 60-month follow-up. Open oral food challenges (OFCs) and serologic tests were performed at the time of initial diagnosis and at 36 ± 3 and 60 ± 3 months. RESULTS: We analyzed 68 patients (39 boys and 29 girls). OFCs were performed in 88.2% of the patients. The egg allergy remission rates were 23.5% and 47.1% by 3 and by 5 years of age, respectively. Persistent egg allergy was significantly associated with moderate to severe AD and house dust mite sensitization. Kaplan-Meier curve analysis revealed that patients with moderate to severe AD had higher persistent egg allergy rates than patients with no and mild AD (p = 0.012). Multivariable analysis identified moderate to severe AD as strongly associated with persistent egg allergy (p = 0.001). CONCLUSIONS: In this study, 47.1% of infants had resolved egg white allergies at 60 months. Moderate to severe AD may be a practical and important prognostic factor for persistent egg allergy in clinical settings.