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1.
Int J Med Inform ; 156: 104598, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34624662

RESUMO

BACKGROUND AND OBJECTIVE: Diabetes and hypertension are two prevalent and related chronic conditions. To inform the design and development of mobile health applications (mHealth apps) for people living with multiple chronic conditions, this paper examines features mentioned in developers' descriptions and user reviews of mHealth apps, along with users' attitudes toward associated features. MATERIALS AND METHODS: Eleven top apps for diabetes and hypertension were identified from Google Play as of January 2020. Based on a stratified sampling strategy, 1,100 user reviews were selected to form the final dataset. Developers' descriptions were also collected for analysis. Using the grounded theory approach, we developed a feature-oriented coding scheme, which was used to identify three levels of features mentioned in app descriptions and user reviews: feature group (the highest level), feature type (the second level), and individual feature (the lowest level). Users' attitudes toward app features mentioned in user reviews were also analyzed. RESULTS: Most top-rated apps for diabetes and hypertension under study were multifeatured, incorporating self-management, information sharing, and decision support features. At the feature-group level, most informative user reviews commented on features related to self-management, followed by decision support and information sharing. The four most frequently mentioned feature types were data entry, data export/import, data visualization, and assessment. Users expressed overwhelming positive attitudes toward app features across all feature categories. Based on users' assessments of existing features and requests for additional features, design implications for app development are provided. CONCLUSIONS: Despite the diversity of app features provided by mHealth apps and users' primarily positive attitudes toward existing app features, more comprehensive and personalized features are expected by app users to satisfy their health needs. Beyond identifying app features in user reviews, future research may seek more in-depth feedback from real-life patients for app development and design using methods like interviews and focus groups, to further enhance the overall quality of relevant mHealth apps to better support users.

2.
Arch Plast Surg ; 48(5): 534-542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34583441

RESUMO

BACKGROUND: During the early stages of lymphedema, active physiologic surgical treatment can be applied. However, lymphedema patients often have limited knowledge and misconceptions regarding lymphedema and surgical treatment. We analyzed the correlations between lymphedema severity and surgical technique according to patients' awareness of surgical treatment for secondary upper extremity lymphedema (UEL). METHODS: Patients with UEL diagnosed between December 2017 and December 2019 were retrospectively evaluated. At the time of their presentation to our hospital for the treatment of lymphedema, they were administered a questionnaire about lymphedema and lymphedema surgery. Based on the results, patients were classified as being aware or unaware of surgical treatment. Lymphedema severity was classified according to the arm dermal backflow (ADB) stage and the MD Anderson Cancer Center (MDACC) stage based on indocyanine green lymphography conducted at presentation. Surgical techniques were compared between the two groups. RESULTS: Patients who were aware of surgical treatment had significantly lower initial ADB and MDACC stages (P<0.05) and more frequently underwent physiologic procedures than excisional procedures (P=0.003). CONCLUSIONS: If patients are actively educated regarding surgical treatment of lymphedema, physiologic procedures may be performed during the early stages of UEL.

3.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360947

RESUMO

The distribution of differential extracellular matrix (ECM) in the lateral and medial menisci can contribute to knee instability, and changes in the meniscus tissue can lead to joint disease. Thus, deep proteomic identification of the lateral and medial meniscus cartilage is expected to provide important information for treatment and diagnosis of various knee joint diseases. We investigated the proteomic profiles of 12 lateral/medial meniscus pairs obtained from excess tissue of osteoarthritis patients who underwent knee arthroscopy surgery using mass spectrometry-based techniques and measured 75 ECM protein levels in the lesions using a multiple reaction monitoring (MRM) assay we developed. A total of 906 meniscus proteins with a 1% false discovery rate (FDR) was identified through a tandem mass tag (TMT) analysis showing that the lateral and medial menisci had similar protein expression profiles. A total of 131 ECM-related proteins was included in meniscus tissues such as collagen, fibronectin, and laminin. Our data showed that 14 ECM protein levels were differentially expressed in lateral and medial lesions (p < 0.05). We present the proteomic characterization of meniscal tissue with mass spectrometry-based comparative proteomic analysis and developed an MRM-based assay of ECM proteins correlated with tissue regeneration. The mass spectrometry dataset has been deposited to the MassIVE repository with the dataset identifier MSV000087753.


Assuntos
Proteínas da Matriz Extracelular/metabolismo , Menisco/metabolismo , Osteoartrite/metabolismo , Proteoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas da Matriz Extracelular/química , Feminino , Humanos , Masculino , Proteoma/química
4.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34451923

RESUMO

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography-tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20-5000) mg and 25.5 (3.03-133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8-95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

5.
Antioxidants (Basel) ; 10(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199555

RESUMO

The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5-43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry-based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI (n = 28) and non-VAKI control subjects (n = 69), consisting of the infection subgroup (n = 23), CKD subgroup (n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation.

6.
Medicine (Baltimore) ; 100(25): e26387, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160417

RESUMO

RATIONALE: Group B Streptococcus (GBS) remains a principal pathogen causing neonatal sepsis and meningitis, particularly in premature infants with relatively insufficient immunity. Recurrence may occur uncommonly, largely associated with subclinical mucosal persistence or repetitive exposure to exogenous sources. White matter injury (WMI) including cystic periventricular leukomalacia (PVL) has been associated with intrauterine infection/inflammation, and neonatal infection as a more significant predictor including postnatal sepsis and recurrent infection, even without microbial neuroinvasion. Furthermore, clinical and experimental evidence of WMI by some bacteria other than GBS without central nervous system invasion has been reported. However, there is little evidence of WMI associated with neonatal GBS sepsis in the absence of meningitis in the literature. PATIENT CONCERNS: A newborn at 30+4 weeks' gestation with low birthweight presented with 2 episodes (with a 13-day interval with no antibiotic therapy) of neonatal sepsis culture-proven for GBS with early-onset presentation after clinical chorioamnionitis via vertical GBS transmission and the associated conditions including prematurity-related neonatal immunodeficiency and persistent mucosal GBS carriage after the first antibiotic treatment. The perinatal GBS infection was complicated by progressive WMI presenting with ventriculomegaly and cystic PVL without a definite evidence of meningitis, intraventricular hemorrhage, and documented cerebral hypoxia or hypoperfusion conditions including septic shock. DIAGNOSES: Recurrent group B streptococcal sepsis and cystic PVL with ventriculomegaly. INTERVENTIONS: Two episodes of GBS sepsis were treated with 15-day parenteral antibiotic therapy, respectively. OUTCOMES: Resolution of the recurrent GBS sepsis without further relapses, however, complicated by WMI and subsequent about 6 months delay in motor development at 12 months' corrected age. LESSONS: This case suggests WMI associated with GBS bacteremia without central nervous system entry by viable GBS and also shows that in premature infants, intrauterine GBS infection with no interventions may lead to extensive and persistent GBS colonization, early-onset and recurrent GBS disease, and WMI. Postnatal as well as intrauterine infection/inflammation controls with maternal prophylaxis may be pivotal for prevention and limiting the magnitude of neurologic injury.


Assuntos
Leucomalácia Periventricular/microbiologia , Sepse Neonatal/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus agalactiae/isolamento & purificação , Administração Intravenosa , Antibacterianos/administração & dosagem , Corioamnionite/diagnóstico , Corioamnionite/microbiologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/microbiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/microbiologia , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Transmissão Vertical de Doenças Infecciosas , Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/patologia , Imageamento por Ressonância Magnética , Masculino , Idade Materna , Sepse Neonatal/diagnóstico , Sepse Neonatal/terapia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Recidiva , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/transmissão , Substância Branca/diagnóstico por imagem , Substância Branca/microbiologia , Substância Branca/patologia , Adulto Jovem
7.
Immun Inflamm Dis ; 9(3): 871-882, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33945658

RESUMO

BACKGROUND: Transglutaminase 2 (TG2), a multifunctional calcium-dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood. OBJECTIVE: To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model. METHODS: TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)-induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild-type mice. The expression of M2 macrophage markers was measured by fluorescence-activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL-4) or IL-13-stimulated expression of M2 macrophage markers was measured in CRL-2456 cells in the presence and absence of a TG2 inhibitor. RESULTS: The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild-type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL-4 or IL-13-stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro. CONCLUSION: Our results suggest that TG2-mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.


Assuntos
Asma , Macrófagos Alveolares , Animais , Humanos , Inflamação , Pulmão , Ativação de Macrófagos , Camundongos
8.
Front Med (Lausanne) ; 8: 652824, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816533

RESUMO

Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-ß signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma.

9.
Drug Des Devel Ther ; 15: 423-440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692613

RESUMO

Background: To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited. Aim: We evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment. Methods: We investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group). Results: A total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008). Conclusion: In non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.


Assuntos
Antibacterianos/farmacocinética , Monitoramento de Medicamentos , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacocinética , Idoso , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento , Vancomicina/administração & dosagem
10.
BMC Pediatr ; 21(1): 49, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33485314

RESUMO

BACKGROUND: Peripheral blood eosinophilia is identified in numerous medical conditions associated with allergic, infectious, and inflammatory processes mostly as reactive eosinophilia with or without tissue eosinophilia. In hospitalized neonates, eosinophilia is common with an inverse relationship with gestational age and occurs solely as mild eosinophilia in the majority of cases. In the literature, eosinophilia has been proposed as a possible risk factor for venous thromboembolism. However, few reports are found on thromboembolic events including portal vein thrombosis (PVT) associated with eosinophilia in the newborn period. Neonates, particularly preterm infants, are vulnerable to thrombosis due to the immature and developing hemostatic system with little reserve capacity, which occurs as catheter-related thrombosis in most cases. CASE PRESENTATION: A male newborn at 34+ 5 weeks' gestation presented with a left portal venous thrombus and hematochezia after initial cow's milk feeding in the setting of blood hypereosinophilia for a prolonged period of time without central venous catheterization. The infant was diagnosed with PVT and food protein-induced allergic proctocolitis (FPIAP) and showed complete resolution of the conditions with expectant management with food avoidance, including the normalized eosinophil count. CONCLUSIONS: Our experience suggests that in the setting of hypereosinophilia with a prolonged duration in premature neonates, FPIAP should be suspected in case of hematochezia in otherwise healthy infants, and considering the increased thrombotic risk by the hypereosinophilia and premature newborn status, evaluation for neonatal thrombosis may be needed, including PVT with the potential risk for the more serious, but uncommon, late complications encompassing portal hypertension.


Assuntos
Eosinofilia , Proctocolite , Trombose , Animais , Bovinos , Eosinofilia/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Veia Porta/diagnóstico por imagem , Proctocolite/complicações , Proctocolite/diagnóstico
11.
Front Pediatr ; 8: 582360, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262962

RESUMO

The prevalence of deformational plagiocephaly (DP) has increased since the recommendation of positioning infants to their back during sleeping and is affected by various biological and environmental factors. This study aimed to investigate associations between DP and perinatal or infant characteristics, including obesity. This case-control study included 135 infants (81 males) aged 2-12 months who were diagnosed with DP using calculated cranial vault asymmetric index and cranial index and 135 age- and sex-matched controls. Motor development was evaluated using the Alberta Infant Motor Scale, and obesity was defined by body mass index. Univariate and multivariate logistic regression models were used to assess potential risk factors for DP and its severity. One hundred thirty-five infants with DP were divided into the following three subgroups according to severity indicated by the cranial vault asymmetry index: mild to moderate group (n = 87, 64.4%), severe group (n = 48, 35.6%), and a combined plagiocephaly and brachycephaly group (n = 79, 58.5%). Independent risk factors significantly associated with development of DP were bottle-only feeding (adjusted odds ratio (aOR) = 4.65; 95% CI: 2.70-8.00), little tummy time when awake (aOR = 3.51, 95% CI: 1.71-7.21), delay of motor development (aOR = 2.85, 95% CI: 1.08-7.49), and obesity at diagnosis (aOR = 2.45, 95% CI: 1.02-5.90). Among these risk factors, delay of motor development (aOR = 4.91, 95% CI: 1.46-16.51) and obesity at diagnosis (aOR = 4.10, 95% CI: 1.42-11.90) were particularly related to severe DP. In conclusion, this study confirms that DP risk is positively associated with bottle-only feeding, infrequent tummy time, and delayed development of motor milestones. Notably, this study demonstrates infant obesity as a new risk factor for DP. Our findings suggest that obesity should be identified early and managed comprehensively in infants with DP.

12.
Asia Pac Allergy ; 10(4): e42, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33178567

RESUMO

Liparis tanakae is a kind of fish in the northwestern Pacific Ocean and sometimes it is used for broth or frozen fish fillets on markets in Korea. A 45-year-old female patient visited Emergency Department because of facial edema, generalized urticaria, dyspnea, and hypotension after eating L. tanakae broth. She recovered after administration of epinephrine. Seven weeks later, she experienced generalized urticaria again after tasting a spoon of L. tanakae broth. In 2 months after recovery, the patient showed positive response to skin prick tests with L. tanakae extract. She also showed positive response to skin prick test with cod which did not induce any symptoms after oral ingestion. The patient was diagnosed as L. tanakae induced anaphylaxis based on the repeated clinical history and skin prick test results. We herein report the first case of L. tanakae induced anaphylaxis.

13.
Medicine (Baltimore) ; 99(40): e22321, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019408

RESUMO

RATIONALE: Congenital syphilis (CS) can manifest as a variety of clinical presentations according to the severity in symptomatic infants during neonatal period. Preterm neonates with CS may have more clinical evidences of infection and be more severely affected by CS compared with term ones. With increasing survival of markedly premature infants for recent decades, CS may be a challenging problem in those with severe manifestations associated with combined pathophysiologies of CS and prematurity. PATIENT CONCERNS: A very low birth weight infant at 32 weeks gestation presented with an unusual CS presentation consisting of prematurity-associated severe neonatal morbidities including meconium obstruction, prolonged cholestatic jaundice with elevated liver enzymes, and disseminated intravascular coagulation with a bleeding diathesis, in addition to common or typical manifestations of CS. DIAGNOSES: Congenital syphilis. INTERVENTIONS: Therapy consisting of a complete course of parenteral penicillin, blood component therapy, proximal ileotomy with inspissated meconium evacuation and distal loop ileostomy, and other conservative treatments. OUTCOMES: Resolution with normal gastrointestinal function and improved liver function was observed. LESSONS: This case suggests that in premature infants CS may manifest as unusual severe neonatal morbidities that may result from combination of syphilitic pathologies and contributors or conditions associated with prematurity including multisystem immaturity.


Assuntos
Recém-Nascido Prematuro/fisiologia , Recém-Nascido de muito Baixo Peso/fisiologia , Sífilis Congênita/fisiopatologia , Sífilis Congênita/terapia , Transfusão de Componentes Sanguíneos/métodos , Feminino , Humanos , Recém-Nascido , Íleo Meconial/cirurgia , Penicilinas/uso terapêutico , Índice de Gravidade de Doença , Sífilis Congênita/diagnóstico
14.
Allergy Asthma Immunol Res ; 12(4): 626-640, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32400129

RESUMO

PURPOSE: Acute exacerbation (AE) is an important domain of asthma management and may be related with ineffective response to corticosteroid. This study aimed to find mechanisms of AE using genome-wide gene expression profiles of blood cells from asthmatics and its perturbation by in vitro dexamethasone (Dex)-treatment. METHODS: We utilized lymphoblastoid B cells from 107 childhood asthmatics and peripheral blood mononuclear cells from 29 adult asthmatics who were treated with inhaled corticosteroids. We searched for a preserved co-expression gene module significantly associated with the AE rate in both cohorts and measured expression changes of genes belong to this module after Dex-treatment. RESULTS: We identified a preserved module composed of 77 genes. Among them, expressions of 2 genes (EIF2AK2 and NOL11) decreased significantly after Dex-treatment in both cohorts. EIF2AK2, a key gene acting antiviral defense mechanism, showed significantly higher expressions in asthmatics with AE. The protein repair pathway was enriched significantly in 64 genes which belong to the preserved module but showed no expression differences after Dex-treatment in both cohorts. Among them, MSRA and MSRB2 may play key roles by controlling oxidative stress. CONCLUSIONS: Many genes belong to the AE rate-associated and preserved module identified in blood cells from childhood and adults asthmatics showed no expression changes after in vitro Dex-treatment. These findings suggest that we may need alternative treatment options to corticosteroids to prevent AE. EIF2AK2, MSRA and MSRB2 expressions on blood cells may help us select AE-susceptible asthmatics and adjust treatments to prevent AE.

15.
Exp Mol Med ; 52(1): 92-104, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31956268

RESUMO

Nonallergic eosinophilic asthma (NAEA) is a clinically distinct subtype of asthma. Thus far, the pathophysiologic mechanisms underlying NAEA have not been fully elucidated. This study aimed to determine the role of IL-23 in the pathogenesis of NAEA. We developed a murine model of NAEA using recombinant IL-23 (rIL-23) plus a nonspecific airway irritant [polyinosinic-polycytidylic acid (polyI:C) or diesel exhaust particles (DEPs)] and investigated whether IL-23 plays an important role in the development of NAEA. Intranasal administration of rIL-23 (0.1 µg/mouse) plus polyI:C (0.01 µg/mouse) or DEPs (10 µg/mouse) without allergen resulted in methacholine bronchial hyperresponsiveness and eosinophilic airway inflammation in mice, which are characteristic features of NAEA. rIL-23 plus a low dose nonspecific airway irritants induced the release of innate cytokines from airway epithelium, including IL-33, thymic stromal lymphopoietin and IL-1ß; these factors activated types 2 and 3 innate lymphoid cells (ILC2s and ILC3s). ILC2s and ILC3s, but not CD4+ T cells (i.e., adaptive immune cells), were important in the development of NAEA. In addition, we observed that IL-23 receptor expressions increased in airway epithelial cells, which suggests the existence of a positive autocrine loop in our murine model of NAEA. To our knowledge, this is the first report in which administration of rIL-23 plus a nonspecific airway irritant (polyI:C or DEPs) without allergen resulted in features of NAEA in mice similar to those found in humans. IL-23 may constitute a therapeutic target for NAEA in humans.

16.
Allergy ; 75(2): 381-391, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31402462

RESUMO

BACKGROUND: Chlorine is widely used in daily life as disinfectant. However, chronic exposure to chlorine products aggravates allergic TH 2 inflammation and airway hyperresponsiveness (AHR). Innate lymphoid cells (ILCs) in airways contribute to the inception of asthma in association with virus infection, pollution, and excess of nutrient, but it is not known whether chronic chlorine exposure can activate innate immune cells. The aim of this study was to evaluate the impact of chlorine inhalation on the innate immunity such as ILCs and macrophages in relation with the development of asthma by using murine ovalbumin (OVA) sensitization/challenge model. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low-dose chlorine exposure by inhalation of naturally vaporized gas of 5% sodium hypochlorite solution. AHR, airway inflammatory cells, from BALF and the population of ILCs and macrophages in the lung were evaluated. RESULTS: The mice exposed to chlorine with OVA (Cl + OVA group) showed enhanced AHR and eosinophilic inflammation compared to OVA-treated mice (OVA group). The population of TH 2 cells, ILC2s, and ILC3s increased in Cl + OVA group compared with OVA group. CD11cint macrophages also remarkably increased in Cl + OVA group compared with OVA group. The deletion of macrophages by clodronate resulted in reduction of ILC2s and ILC3s population which was restored by adoptive transfer of CD11cint macrophages. CONCLUSIONS: Chronic chlorine inhalation contributes to the exacerbation of airway inflammation in asthmatic airway by mobilizing pro-inflammatory macrophage into the lung as well as stimulating group 2 and 3 ILCs.


Assuntos
Asma/imunologia , Antígenos CD11/metabolismo , Cloro/farmacologia , Imunidade Inata , Macrófagos/imunologia , Células Th2/imunologia , Administração por Inalação , Animais , Asma/induzido quimicamente , Cloro/administração & dosagem , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Pulmão/imunologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos
17.
J Korean Med Sci ; 34(49): e315, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31858755

RESUMO

BACKGROUND: Community acquired-methicillin resistant Staphylococcus aureus (MRSA) clones, including ST1, ST8, and ST30 are reported worldwide. However, data among Korean children are limited. Thus, we investigated the molecular characteristics of S. aureus among children in Korea. METHODS: S. aureus isolated from Korean children diagnosed with skin and soft tissue infection (SSTI) or bone and joint infection due to S. aureus infection at Seoul National University Bundang Hospital, from August 2010 to November 2016, were analyzed for multilocus sequence type (ST) and SCCmec typing. Polymerase chain reaction of Panton-Valentine leukocidin (PVL), qac A/B, smr and mupA genes were also performed. Electronic medical records were reviewed for clinical data and antibiotic susceptibility results. Cases were classified into three groups: health care-associated community-onset (HACO) infections, hospital-onset (HO) infections, and community-acquired (CA) infections. RESULTS: A total of 67 strains from children with SSTI (41/67, 61.2%) and bone and joint infection (26/67, 38.8%) were included. Among all isolates, 29.9% (20/67) were MRSA, and 70% (14/20) were classified as CA, 20% (4/20) as HACO and 10% (2/20) as HO infections. MRSA rate according to disease was 34.1% (14/41) for SSTI and 23.1% (6/26) for bone and joint infection. MRSA strains included ST72-SCCmec IV (14/20, 70.0%), ST5-SCCmec II (3/20, 15.0%) and ST1-SCCmec IV (2/20, 10.0%). ST30 was the most common cause of SSTI and bone and joint infections and 96.6% (28/29) were methicillin-susceptible Staphylococcus aureus (MSSA). PVL genes were detected in 3 strains (3.8%, ST30-SCCmec IV n = 1, MSSA ST30 n = 2), qac A/B in 3 (MRSA = 3), smr in 3 (MSSA = 1, MRSA = 2) and mupA in 7 (MRSA = 5, MSSA = 2). CONCLUSION: Molecular epidemiology of S. aureus in Korean children with SSTI and bone and joint infection showed that ST30 was predominant and mostly MSSA. Among MRSA, ST72-SCCmec type IV was the most common strain.


Assuntos
Doenças Ósseas/diagnóstico , Artropatias/diagnóstico , Infecções dos Tecidos Moles/diagnóstico , Infecções Cutâneas Estafilocócicas/diagnóstico , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Doenças Ósseas/epidemiologia , Doenças Ósseas/microbiologia , Criança , Pré-Escolar , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Lactente , Recém-Nascido , Artropatias/epidemiologia , Artropatias/microbiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Tipagem de Sequências Multilocus , República da Coreia/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação
18.
PLoS One ; 14(10): e0224450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661511

RESUMO

BACKGROUND: The aim of this study was to investigate whether some associations between histological chorioamnionitis (HCA) and favorable neonatal outcomes might be linked to those of antenatal steroids (AS) by determining the separate as well as the combined associations of HCA and AS with neonatal outcomes in very low birth weight infants (VLBWIs). METHODS: This was a population-based study of VLBWIs born at 20-33 weeks' gestation between January 2013 and December 2015 from the Korean Neonatal Network. A total of 4652 VLBWIs were enrolled for prevalence study. Of these, 2900 singleton VLBWIs were used for outcome analyses to evaluate individual associations of HCA and AS simultaneously with correction for potential perinatal factors and an interaction term of HCA and AS. RESULTS: The overall prevalence of HCA was 34.9% (1623 VLBWIs). Multivariable logistic regression demonstrated that HCA was associated with decreased mortality (adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.29-0.91; P = 0.022), AS were associated with reduction in mortality (aOR, 0.59; 95% CI, 0.39-0.90; P = 0.014) and neonatal seizure (aOR, 0.57; 95% CI, 0.37-0.86; P = 0.008), and a combination of HCA and AS was associated with remarkably lowered severe intraventricular hemorrhage by interacting with each other (aOR, 0.47; 95% CI, 0.25-0.88; P = 0.019). CONCLUSIONS: We suggest that in VLBWIs HCA and AS may be favorable independent factors for neonatal outcome and may also work in synergy for neuroprotection.


Assuntos
Corioamnionite/epidemiologia , Citocinas/análise , Resultado da Gravidez/epidemiologia , Adulto , Citocinas/sangue , Feminino , Idade Gestacional , Número de Gestações , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso/fisiologia , Interleucina-1/análise , Interleucina-6/análise , Modelos Logísticos , Masculino , Paridade , Gravidez , Diagnóstico Pré-Natal/métodos , República da Coreia/epidemiologia , Estudos Retrospectivos , Esteroides/análise , Fator de Necrose Tumoral alfa/análise
20.
J Mol Med (Berl) ; 97(7): 951-956, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119301

RESUMO

The original publication of this paper contains a mistake.

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