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Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.

ObjectiveTryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.MethodWe analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.ResultsTryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.ConclusionHigher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

Abstract Introduction Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness. Methods This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV1) after treatment versus at inclusion. Results In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters. Conclusion TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV1.

IntroductionWith increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians’ opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries.MethodsWe adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries.ResultsRegionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer.Discussion and conclusionOur study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.

BackgroundChronic granulomatous disease (CGD) is an inborn error of immunity (IEI) disorder that results from defects in the respiratory burst activity in phagocytes, leading to the inability to kill bacterial and fungal microorganisms. CGD patients usually have a high incidence of morbidity such as infections and autoinflammatory diseases and a high mortality rate. Allogeneic bone marrow transplantation (BMT) is the only definitive cure for patients who suffer from CGD.Case presentationWe report the first transplant case of chronic granulomatous disease in Vietnam. A 25-month-old boy with X-linked CGD underwent bone marrow transplantation from his 5-year-old, full-matched human leukocyte antigen (HLA)-carrier sibling after myeloablative conditioning regimen with busulfan 5.1 mg/kg/day for 4 days, fludarabine 30 mg/m2/day for 5 days, and rATG (Grafalon-Fresenius) 10 mg/kg/day for 4 days. Neutrophil was engrafted on day 13 posttransplant, donor chimerism was 100% on day 30 with the dihydrorhodamine-1,2,3 (DHR 123) flow cytometric assay test that reached 38% of the normal 45 days posttransplant. Five months after transplant, the patient was free of infection with stable DHR 123 assay at 37%, and donor chimerism remained 100%. No sign of a graft-versus-host disease had been observed posttransplant.ConclusionWe suggest that bone marrow transplantation is a safe and effectual cure for CGD patients, especially for patients with HLA-identical siblings.

BackgroundAsthma and obstructive sleep apnea (OSA) are common chronic respiratory disorders in children. The relationship between asthma and OSA is bidirectional; these conditions share multiple epidemiological risk factors. Untreated OSA may cause attention deficit hyperactivity disorder (ADHD) symptoms. This study aimed to assess the prevalence of ADHD in asthmatic children with OSA and the link between asthma control and lung function of children with asthma and OSA.MethodsA total of 96 children aged 6–15 years diagnosed with asthma, according to the Global Initiative for Asthma (GINA) 2020, were enrolled in this study. All demographic data, including age, gender, body mass index, asthma control status, therapy, the Vanderbilt ADHD Diagnostic Parent Rating Scale, lung function, and exhaled nitric oxide, were collected. In addition, home respiratory polygraphy was used to identify OSA in study subjects.ResultsA total of 96 patients (8.4 ± 2.4 years) were included in the present study. OSA was identified in 60.4% of asthmatic children with a mean apnea-hypopnea index (AHI) of 3.5 ± 3.0 event/h. The inattentive ADHD subtype was significantly lower in the non-OSA asthmatic group than in the OSA asthmatic group (7.9 vs. 34.5%, p < 0.05). ADHD had a higher probability of presence (OR: 3.355; 95% CI: 1.271–8.859; p < 0.05) in the OSA group (AHI >1 event/h). Children with poorly controlled asthma had a significantly high risk of OSA (83.0 vs. 17.0%, p < 0.001) than children with well-controlled asthma. Allergic rhinitis increased the odds of having OSA in patients with asthma [OR: 8.217 (95% CI: 3.216–20.996); p < 0.05].ConclusionThe prevalence of OSA is increased among poorly controlled asthma. ADHD may have a higher prevalence in children with OSA. Therefore, prompt diagnosis of OSA will lead to an accurate asthma control strategy in patients with asthma.

BackgroundObstructive sleep apnea (OSA) is the most common form of respiratory disorders during sleep in children, especially those with severe asthma. However, optimal treatment of asthma might significantly improve OSA severity.MethodsIt was a cohort study including children aged >5 years old and diagnosed with asthma according to GINA (Global Initiative for Asthma). The data related to age, gender, height, weight, body mass index (BMI), clinical symptoms and medical history of asthma, spirometry (FEV1: forced expiratory in 1 s), and exhaled nitric oxide (FENO) were recorded for analysis. Respiratory polygraphy (RPG) was done for each study subject to diagnose OSA and its severity.ResultsAmong 139 asthmatic children, 99 patients with OSA (71.2%) were included in the present study (9.3 ± 0.2 years): 58.6% with uncontrolled asthma and 32.3% with partial controlled asthma. The mean ACT (asthma control testing) score was 19.0 ± 3.4. The most frequent night-time symptoms were restless sleep (76.8%), snoring (61.6%), sweating (52.5%), and trouble breathing during sleep (48.5%). The common daytime symptoms were irritable status (46.5%) and abnormal behavior (30.3%). The mean AHI (apnea-hypopnea index) was 3.5 ± 4.0 events/h. There was a significant correlation between BMI and snoring index (R = 0.189 and P = 0.027), bronchial and nasal FENO with AHI (R = 0.046 and P < 0.001; R = 0.037 and P < 0.001; respectively). There was no significant correlation between asthma level, FEV1 and AHI. The severity of asthma and respiratory function were improved significantly after 3 months and 6 months of asthma treatment in combination with leukotriene receptor antagonist (LRA) treatment. The symptoms related to OSA were significantly improved after treatment with LRA. The severity of OSA was decreased significantly after 3 months and 6 months of treatment.ConclusionThe treatment of asthmatic children with comorbid OSA by LRA in combination with standard therapy for asthma could improve the control of asthma and the symptoms and severity of OSA.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

This study investigated the impact of value consonance on employee-based brand equity through the mediating role of teachers' self-efficacy and belongingness. For this purpose, a deductive approach was followed, and data were collected under a cross-sectional research design from academia through a questionnaire. Prior approval from the administration was sought before administrating the questionnaire on a large scale and a sample of 520 teachers was approached in the first phase. At this stage, 418 answered questionnaires were received, while in the second wave, questions related to the teacher's self-efficacy and employee-based brand equity were asked from the respondents. Out of these 418 re-distributed questionnaires, 387 were received back and after discarding the partially filled and incomplete questionnaires, the useable sample size was left as 372. Data have been analyzed by using the structural equation modeling technique, which was assessed through measurement and structural model. Results indicate that value consonance can promote positive behaviors in the workplace. Moreover, teachers with high self-efficacy can develop based on brand equity. Similarly, employees with high-value consonance develop a sense of belongingness with their academic institutes. Limitations and future directions are also discussed.

This study focuses on the relationship between economic growth and environmental degradation, by testing the Environmental Kuznets Curve hypothesis in Vietnam, a main export‐oriented country that features a long period of economic growth. The main originality of this work is that, unlike previous studies, it uses ecological footprint as the main indicator for environmental degradation. This allows to reconsider the results from previous studies that only focus on CO2 emissions performances. The cointegration between the analysed variables is investigated using the autoregressive distributed lag (ARDL) approach. To determine the parameters of the Environmental Kuznets Curve in the sample, this work additionally analyses long‐ and short‐run estimations. The paper shows that the EKC hypothesis holds in the long term for Vietnam when using ecological footprint. Nevertheless, it also shows that not only growth but also primary energy consumption contributes to increased environmental destruction. An active ecological policy and the decrease of fossil energy use seem necessary to allow Vietnam to keep a high level of economic growth and reduce environmental degradation. [ABSTRACT FROM AUTHOR]

BackgroundStevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare and life-threatening disease of the skin and mucosal surfaces. Although gastrointestinal manifestations in adults are potential prognostic factors for disease severity, there are limited data on such cases and their standard management in the pediatric population.Case PresentationWe herein report the case of an 8-year-old girl with a 1-year history of epilepsy, who presented with bilateral conjunctivitis and progressively widespread bullous, and pruritic eruption based on erythematous skin after administration of carbamazepine. A diagnosis of carbamazepine-induced TEN was made, and the drug was immediately discontinued. The result of genetic screening showed that the patient was positive for the HLA-B*15:02 allele. Then, her condition got worse by developing gastrointestinal involvement, including hematemesis and severe watery bloody diarrhea. A combination of the intravenous immunoglobulin and the appropriate dose of systemic steroids have contributed to a favorable outcome in this case. Multidisciplinary care of mucocutaneous involvement, supplemental nutrition, and fluid replacement was also critically warranted. This report aims to contribute to the current literature on TEN-related gastrointestinal manifestations in pediatrics and highlights the need for further investigations in determining the optimal treatment in such cases.ConclusionIn conclusion, we reported the successful treatment of TEN-related gastrointestinal manifestations in a pediatric patient, which should be critically considered in patients with SJS/TEN. Since it may significantly contribute to the poor prognosis of the illness, further investigations in determining standard management in such cases are necessary.

This study is aimed to bring baby clam broth (BCB) into antioxidant proteolysate utilizing enzymatic hydrolysis. Chemical compositions of BCB were firstly analyzed, followed by investigating the effects of enzymatic hydrolysis parameters involving in enzyme type, pH, temperature, enzyme:substrate (E:S) ratio and hydrolysis time on antioxidant of BCB proteolysate. It can be seen from the result that the BCB owned the moisture content, protein content, lipid content, and ash content of 97.55±0.89%, 1.52±0.16%, 0.09±0.02%, and 0.37±0.04%, respectively. The BCB proteolysate, under the hydrolysis condition including Flavourzyme, pH 7, 50°C, E:S ratio of 5 U/g protein and hydrolysis time of 50 min, exhibited the highest 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) cation ratio (ABTS●+) scavenging activity of 770.67±28.33 µM Trolox Equivalent (µM TE) (7.1 and 2.5 times lower than those of vitamin C and butylated hydroxytoluene (BHT), in order) and ferric reducing antioxidant power (FRAP) value of 245.26±7.37 µM TE (11.6 and 4.0 folds lower than those of vitamin C and BHT, respectively). This study suggests a new use of the BCB, antioxidant proteolysate which could be applied as a functional food or natural antioxidant additive, substituting for synthetic compounds.

Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training.Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan.Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation.Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI (r = −0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI (r = −0.788, p < 0.001; r = −0.739, p = 0.002). HDI positively correlated with average testing level (r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently.Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research.

Changes of the blood vessels and collagen are associated with the development of abnormal cervical cells. Recently, optical coherence tomography and Mueller polarization images were used to provide information regarding the presence of collagen fibers in the cervical tissue. However, most of these methods need a lot of time for image recording and are expensive. In addition, the general survey on the absorption and distribution characteristics of collagen and blood in the cervical is still lacking. In this study, we developed a colposcopy combining cross-polarized image and image processing algorithm with an efficient analytical model to map the distribution of blood and collagen in the uterine. For this system’s proof of concept, we captured and processed the case of cervical ectopy and Nabothian cyst. The results show that the distribution of blood and collagen maps matched with anatomical and physiological when compared with Lugol’s iodine images. This technology has some advantages, such as low cost, real time, and can replace the use of acetic acid or Lugol’s iodine in the future.