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Turmeric (Curcuma longa L.) extract (CLE) has been shown to elicit several pharmacological properties and is widely used in Asian traditional medicine. Herein, we assessed the impact of CLE on airway inflammation in BALB/c mice and A549 cells to clarify the underlying mechanism. An asthmatic mouse model was established by administering ovalbumin (OVA). CLE (100 or 300 mg/kg/day) was orally administered daily from days 18 to 23, with dexamethasone (3 mg/kg/day) used as the positive control. Human airway epithelial cells, A549, were stimulated using recombinant tumor necrosis factor-α. The CLE100 and CLE400 groups exhibited a significant downregulation in eosinophil counts, cytokine levels, and immunoglobulin-E levels. Moreover, CLE administration dose-dependently suppressed oxidative stress and airway inflammation in the lung tissue. CLE administration inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expression and activity of matrix metalloproteinase (MMP)-9. In vitro, CLE treatment reduced mRNA levels of proinflammatory cytokines, MAPK phosphorylation, and the expression and activity of MMP-2 and MMP-9. Additionally, 50 µg/mL CLE and 2.5 µg/mL curcumin showed similar anti-inflammatory effects. Collectively, our findings revealed that CLE could suppress airway inflammation in asthmatic mice and A549 cells via oxidative stress-driven MAPK/MMPs signaling, suggesting that CLE could be developed as a potential treatment option for patients with asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pathogens generate and secrete effector proteins to the host plant cells during pathogenesis to promote virulence and colonization. If the plant carries resistance (R) proteins that recognize pathogen effectors, effector-triggered immunity (ETI) is activated, resulting in a robust immune response and hypersensitive response (HR). The bipartite effector AvrRps4 from Pseudomonas syringae pv. pisi has been well studied in terms of avirulence function. In planta, AvrRps4 is processed into two parts. The C-terminal fragment of AvrRps4 (AvrRps4 C ) induces HR in turnip and is recognized by the paired resistance proteins AtRRS1/AtRPS4 in Arabidopsis. Here, we show that AvrRps4 C targets a group of Arabidopsis WRKY, including WRKY46, WRKY53, WRKY54, and WRKY70, to induce its virulence function. Indeed, AvrRps4 C suppresses the general binding and transcriptional activities of immune-positive regulator WRKY54 and WRKY54-mediated resistance. AvrRps4 C interferes with WRKY54's binding activity to target gene SARD1 in vitro, suggesting WRKY54 is sequestered from the SARD1 promoter by AvrRps4 C . Through the interaction of AvrRps4 C with four WRKYs, AvrRps4 enhances the formation of homo-/heterotypic complexes of four WRKYs and sequesters them in the cytoplasm, thus inhibiting their function in plant immunity. Together, our results provide a detailed virulence mechanism of AvrRps4 through its C-terminus., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB's diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB's clinical application in the presence of colitis.

Ageratum conyzoides , an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.

Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen-binding domains and costimulatory domains to induce T cell activation but can only react against target cells with relatively high amounts of antigen. TCRs have a much lower affinity for their antigens but can react against target cells displaying only a few antigen molecules. Here, we describe a new type of receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. In Co-STARs, the antigen-recognizing components of TCRs are replaced by high-affinity antibody fragments, and costimulation is provided by two modules that drive NF-κB signaling (MyD88 and CD40). Using a TCR-mimic antibody fragment that targets a recurrent p53 neoantigen presented in a common human leukocyte antigen (HLA) allele, we demonstrate that T cells equipped with Co-STARs can kill cancer cells bearing low densities of antigen better than T cells engineered with conventional CARs and patient-derived TCRs in vitro. In mouse models, we show that Co-STARs mediate more robust T cell expansion and more durable tumor regressions than TCRs similarly modified with MyD88 and CD40 costimulation. Our data suggest that Co-STARs may have utility for other peptide-HLA antigens in cancer and other targets where antigen density may limit the efficacy of engineered T cells.

Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement., Competing Interests: Authors D-RL, B-KC were employed by NUON Co., Ltd. Authors J-HL were employed by EveryH Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Jeong, Kim, Chung, Kim, Lee, Choi, Lim, Ko and Kim.)

Objective: COVID-19 has been associated with myocardial involvement in collegiate athletes. The first report from the Big Ten COVID-19 Cardiac Registry (Registry) was an ecological study that reported myocarditis in 37 of 1597 athletes (2.3%) based on local clinical diagnosis. Our objective was to assess the relationship between athlete and clinical characteristics and myocardial involvement., Design: Cross-sectional study., Setting: We analyzed data from 1218 COVID-19 positive Big Ten collegiate athletes who provided informed consent to participate in the Registry., Participants: 1218 athletes with a COVID-19-positive PCR test before June 1, 2021., Assessment of Independent Variables: Demographic and clinical characteristics of athletes were obtained from the medical record., Main Outcome Measures: Myocardial involvement was diagnosed based on local clinical, cardiac magnetic resonance (CMR), electrocardiography, troponin assay, and echocardiography. We assessed the association of clinical factors with myocardial involvement using logistic regression and estimated the area under the receiver operating characteristic (ROC) curve., Results: 25 of 1218 (2.0%) athletes met criteria for myocardial involvement. The logistic regression model used to predict myocardial involvement contained indicator variables for chest pain, new exercise intolerance, abnormal echocardiogram (echo), and abnormal troponin. The area under the ROC curve for these indicators was 0.714. The presence of any of these 4 factors in a collegiate athlete who tested positive for COVID-19 would capture 55.6% of cases. Among noncases without missing data, 86.9% would not be flagged for possible myocardial involvement., Conclusion: Myocardial involvement was infrequent. We predicted case status with good specificity but deficient sensitivity. A diagnostic approach for myocardial involvement based exclusively on symptoms would be less sensitive than one based on symptoms, echo, and troponin level evaluations. Abnormality of any of these evaluations would be an indication for CMR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIP Cre ) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIP Cre mice, despite being TXNIP deficient, TXNIP Cre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Polyhexamethylene guanidine (PHMG) is a positively charged polymer used as a disinfectant that kills microbes but can cause pulmonary fibrosis if inhaled. After the long-term risks were confirmed in South Korea, it became crucial to measure toxicity through diverse surrogate biomarkers, not only proteins, especially after these hazardous chemicals had cleared from the body. These biomarkers, identified by their biological functions rather than simple numerical calculations, effectively explained the imbalance of pulmonary surfactant caused by fibrosis from PHMG exposure. These long-term studies on children exposed to PHMG has shown that blood protein indicators, primarily related to apolipoproteins and extracellular matrix, can distinguish the degree of exposure to humidifier disinfectants (HDs). We defined the extreme gradient boosting models and computed reflection scores based on just ten selected proteins, which were also verified in adult women exposed to HD. The reflection scores successfully discriminated between the HD-exposed and unexposed groups in both children and adult females (AUROC: 0.957 and 0.974, respectively) and had a strong negative correlation with lung function indicators. Even after an average of more than 10 years, blood is still considered a meaningful specimen for assessing the impact of environmental exposure to toxic substances, with proteins providing in identifying the pathological severity of such conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Palpitations are a common reason for athletes to seek medical care. Although often benign, palpitations may serve as a harbinger for underling cardiac pathology. Given the unique challenges in this population, this review will serve to discuss the basic underlying pathophysiology, which may predispose athletes to palpitations. In addition, we will review the aetiologies, diagnostic evaluation, management and counselling strategies for some of the most common diagnoses seen in athletes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Youth and adult participation in sports continues to increase, and athletes may be diagnosed with potentially arrhythmogenic cardiac conditions. This international multidisciplinary document is intended to guide electrophysiologists, sports cardiologists, and associated health care team members in the diagnosis, treatment, and management of arrhythmic conditions in the athlete with the goal of facilitating return to sport and avoiding the harm caused by restriction. Expert, disease-specific risk assessment in the context of athlete symptoms and diagnoses is emphasized throughout the document. After appropriate risk assessment, management of arrhythmias geared toward return to play when possible is addressed. Other topics include shared decision-making and emergency action planning. The goal of this document is to provide evidence-based recommendations impacting all areas in the care of athletes with arrhythmic conditions. Areas in need of further study are also discussed., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated., Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro , we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors., Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels., Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Kim, Jeong, Kim, Chung, Kim, Hong, Kwon, Ko and Kim.)

Purpose: To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid., Methods: A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35-37, 38-39, 40-42, 43-44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 $USD. Model outcomes were sub-stratified by degree and type of mosaicism., Results: For patients younger than 43, an additional cycle of IVF with PGT-A resulted in a higher relative live birth rate (<35, +20%; 35-37, +15%; 38-39, +17%; 40-42, +6%; average, +14.5%) compared to mosaic embryo transfer with an average additional cost of $16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43-44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A., Conclusion: Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. Periprocedural conduction system damage was a primary concern during AVNRT ablation. This study aimed to assess the incidence of permanent atrioventricular (AV) block and the success rate associated with different types of catheters in slow pathway ablation., Method: A literature search was performed to identify studies that compared various techniques, including types of radiofrequency ablation (irrigated and nonirrigated) and different sizes of catheter tip cryoablation (4, 6, and 8-mm), in terms of their outcomes related to permanent atrioventricular block and success rate. To assess and rank the treatments for the different outcomes, a random-effects model of network meta-analysis, along with p-scores, was employed., Results: A total of 27 studies with 5110 patients were included in the analysis. Overall success rates ranged from 89.78% to 100%. Point estimation showed 4-mm cryoablation exhibited an odds ratio of 0.649 (95%CI: 0.202-2.087) when compared to nonirrigated RFA. Similarly, 6-mm cryoablation had an odds ratio of 0.944 (95%CI: 0.307-2.905), 8-mm cryoablation had an odds ratio of 0.848 (95%CI: 0.089-8.107), and irrigated RFA had an odds ratio of 0.424 (95%CI: 0.058-3.121) compared to nonirrigated RFA., Conclusion: Our study found no significant difference in the incidence of permanent AV block between the types of catheters. The success rates were consistently high across all groups. These findings emphasize the potential of both RF ablation (irrigated and nonirrigated catheter) and cryoablation as viable options for the treatment of AVNRT, with similar safety and efficacy profile., (© 2024 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Objective: Patients with chronic stroke capable of independent gait were classified into functional ambulation category (FAC) 4 or 5, and the kinetic and kinematic data on their lower limb joints on the affected and unaffected sides were compared with that of healthy individuals. Finally, the qualitative changes in the gait of patients with stroke were investigated based on the differences in FAC scores. Methods: Twelve healthy participants and 19 patients with stroke capable of independent gait were included. The three-dimensional (3D) motion analysis and conventional assessment were conducted for all patients with stroke. Results: The FAC 5 group exhibited a larger range of motion (ROM) than the FAC 4 group in knee and hip joints on the affected side and only in the hip on the unaffected side. In the FAC 5 group, ROM differences in the healthy group on either the affected or unaffected side were absent. The peak of the hip flexion moment on the affected side in both the FAC 4 and 5 groups was smaller than that in the healthy group and in the FAC 4 group on the unaffected side. The absorption power minimum on the affected side was smaller only in the FAC 4 group than that in the healthy group and was larger in the FAC 5 group than that in the FAC 4 group. On the unaffected side, the absorption power minimum was smaller only in the FAC 4 group than that in the healthy group. Conclusion: Functional differences in gait were found in patients classified based on conventional evaluation capable of independent gait after post-stroke rehabilitation. Patients may not exhibit complete recovery in the kinetic indices even if they are judged to be normal in the conventional evaluation, and the kinematic gait indices indicate recovery. Evaluating kinetic indices in addition to kinematic indices is necessary, and joint power may be an especially useful index., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeon, Chung, Bak, Kim, Shin, Baek and Kim.)

Background: Pectobacterium species are necrotrophic phytopathogenic bacteria that cause soft rot disease in economically important crops. The successful infection of host plants relies on interactions among virulence factors, competition, and transmission within hosts. Pectobacteria primarily produce and secrete plant cell-wall degrading enzymes (PCWDEs) for virulence. The regulation of PCWDEs is controlled by quorum sensing (QS). Thus, the QS system is crucial for disease development in pectobacteria through PCWDEs., Results: In this study, we identified a Tn-insertion mutant, M2, in the expI gene from a transposon mutant library of P. carotovorum subsp. carotovorum Pcc21 (hereafter Pcc21). The mutant exhibited reduced production and secretion of PCWDEs, impaired flagellar motility, and increased sensitivity to hydrogen peroxide, resulting in attenuated soft rot symptoms in cabbage and potato tubers. Transcriptomic analysis revealed the down-regulation of genes involved in the production and secretion in the mutant, consistent with the observed phenotype. Furthermore, the Pcc21 wild-type transiently colonized in the gut of Drosophila melanogaster within 12 h after feeding, while the mutant compromised colonization phenotype. Interestingly, Pcc21 produces a bacteriocin, carocin D, to compete with other bacteria. The mutant exhibited up-regulation of carocin D-encoding genes (caroDK) and inhibited the growth of a closely related bacterium, P. wasabiae., Conclusion: Our results demonstrated the significance of ExpI in the overall pathogenic lifestyle of Pcc21, including virulence, competition, and colonization in plant and insect hosts. These findings suggest that disease outcome is a result of complex interactions mediated by ExpI across multiple steps. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea., Methods: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients., Results: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes ( RPGR , HYDIN , NME5 ) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points., Conclusions: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Routine exercise leads to cardiovascular adaptations that differ based on sex. Use of cardiac testing to screen athletes has driven research to define how these sex-based adaptations manifest on the electrocardiogram and cardiac imaging. Importantly, sex-based differences in cardiovascular structure and outcomes in athletes often parallel findings in the general population, underscoring the importance of understanding their mechanisms. Substantial gaps exist in the understanding of why cardiovascular adaptations and outcomes related to exercise differ by sex because of underrepresentation of female participants in research. As female sports participation rates have increased dramatically over several decades, it also remains unknown if differences observed in older athletes reflect biological mechanisms vs less lifetime access to sports in females. In this review, we will assess the effect of sex on cardiovascular adaptations and outcomes related to exercise, identify the impact of sex hormones on exercise performance, and highlight key areas for future research., Competing Interests: Funding Support and Author Disclosures Dr Kim has received compensation for his role as team cardiologist for the Atlanta Falcons. Dr Phelan has served as a consultant for Caption Health, Bristol Myers Squibb, and Pfizer. Dr Lampert has received compensation for research support and honoraria from and is on the Advisory Board for Medtronic; has received honoraria and research support from Abbott/St Jude; and has received research support from Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified., (Copyright © 2023 The Heart Rhythm Society, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice., Methods: Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group., Results: Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change., Conclusion: These results indicate inotodiol can help suppress allergic responses by immunomodulation activities., (© 2022 ARS-AAOA, LLC.)

Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific therapeutic targets. MANAs are HLA-presented (pHLA) peptides derived from intracellular mutant proteins that are otherwise inaccessible to antibody-based therapeutics. Here, we describe the cryo-EM structure of an antibody-MANA pHLA complex. Specifically, we determine a TCR mimic (TCRm) antibody bound to its MANA target, the KRAS G12V peptide presented by HLA-A*03:01. Hydrophobic residues appear to account for the specificity of the mutant G12V residue. We also determine the structure of the wild-type G12 peptide bound to HLA-A*03:01, using X-ray crystallography. Based on these structures, we perform screens to validate the key residues required for peptide specificity. These experiments led us to a model for discrimination between the mutant and the wild-type peptides presented on HLA-A*03:01 based exclusively on hydrophobic interactions., (© 2023. Springer Nature Limited.)

Recognition of pathogen effectors is a crucial step for triggering plant immunity. Resistance (R) genes often encode for nucleotide-binding leucine-rich repeat receptors (NLRs), and NLRs detect effectors from pathogens to trigger effector-triggered immunity (ETI). NLR recognition of effectors is observed in diverse forms where NLRs directly interact with effectors or indirectly detect effectors by monitoring host guardees/decoys (HGDs). HGDs undergo different biochemical modifications by diverse effectors and expand the effector recognition spectrum of NLRs, contributing robustness to plant immunity. Interestingly, in many cases of the indirect recognition of effectors, HGD families targeted by effectors are conserved across the plant species while NLRs are not. Notably, a family of diversified HGDs can activate multiple non-orthologous NLRs across plant species. Further investigation on HGDs would reveal the mechanistic basis of how the diversification of HGDs confers novel effector recognition by NLRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The ever-growing world population, increasingly frequent extreme weather events and conditions, emergence of novel devastating crop pathogens and the social strive for quality food products represent a huge challenge for current and future agricultural production systems. To address these challenges and find realistic solutions, it is becoming more important by the day to understand the complex interactions between plants and the environment, mainly the associated organisms, but in particular pathogens. In the past several years, research in the fields of plant pathology and plant-microbe interactions has enabled tremendous progress in understanding how certain receptor-based plant innate immune systems function to successfully prevent infections and diseases. In this review, we highlight and discuss some of these new ground-breaking discoveries and point out strategies of how pathogens counteract the function of important core convergence hubs of the plant immune system. For practical reasons, we specifically place emphasis on potential applications that can be detracted by such discoveries and what challenges the future of agriculture has to face, but also how these challenges could be tackled., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences., Purpose: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV., Methods: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay., Results: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms., Conclusion: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination findings, and laboratory and radiology results.

Plant pathogenic Pectobacterium species cause severe soft rot/blackleg diseases in many economically important crops worldwide. Pectobacterium utilizes plant cell wall degrading enzymes (PCWDEs) as the main virulence determinants for its pathogenicity. In this study, we screened a random mutant, M29 is a transposon insertion mutation in the metC gene encoding cystathionine β-lyase that catalyzes cystathionine to homocysteine at the penultimate step in methionine biosynthesis. M29 became a methionine auxotroph and resulted in growth defects in methionine-limited conditions. Impaired growth was restored with exogenous methionine or homocysteine rather than cystathionine. The mutant exhibited reduced soft rot symptoms in Chinese cabbages and potato tubers, maintaining activities of PCWDEs and swimming motility. The mutant was unable to proliferate in both Chinese cabbages and potato tubers. The reduced virulence was partially restored by a complemented strain or 100 µM of methionine, whereas it was fully restored by the extremely high concentration (1 mM). Our transcriptomic analysis showed that genes involved in methionine biosynthesis or transporter were downregulated in the mutant. Our results demonstrate that MetC is important for methionine biosynthesis and transporter and influences its virulence through Pcc21 multiplication in plant hosts.

Introduction: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). The importance of primary prevention of sudden cardiac death (SCD) in Brugada syndrome is well recognized; however, ventricular arrhythmia risk stratification remains challenging and controversial. We aimed to assess the association of type of syncope with MAE via systematic review and meta-analysis., Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2021. Included studies were cohort (prospective or retrospective) studies that reported the types of syncope (cardiac, unexplained, vasovagal, and undifferentiated) and MAE. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the odds ratio (OR) and 95% confidence intervals (CIs)., Results: Seventeen studies from 2005 to 2019 were included in this meta-analysis involving 4355 Brugada syndrome patients. Overall, syncope was significantly associated with an increased risk of MAE in Brugada syndrome (OR = 3.90, 95% CI: 2.22-6.85, p  < .001, I 2  = 76.0%). By syncope type, cardiac (OR = 4.48, 95% CI: 2.87-7.01, p  < .001, I 2  = 0.0%) and unexplained (OR = 4.71, 95% CI: 1.34-16.57, p  = .016, I 2  = 37.3%) syncope was significantly associated with increased risk of MAE in Brugada syndrome. Vasovagal (OR = 2.90, 95% CI: 0.09-98.45, p  = .554, I 2  = 70.9%) and undifferentiated syncope (OR = 2.01, 95% CI: 1.00-4.03, p  = .050, I 2  = 64.6%, respectively) were not., Conclusion: Our study demonstrated that cardiac and unexplained syncope was associated with MAE risk in Brugada syndrome populations but not in vasovagal syncope and undifferentiated syncope. Unexplained syncope is associated with a similar increased risk of MAE compared to cardiac syncope., Competing Interests: None to declare., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Objective: To assess recall bias by evaluating how well female cancer survivors remember details regarding their cancer diagnosis, treatment, and fertility preservation (FP) counseling.Oncofertility literature cites recall bias as a pitfall of retrospective surveys, but limited data exist to quantify this bias., Design: Retrospective secondary analysis of cross-sectional survey data., Setting: Single academic medical center., Patients: Female oncology patients of reproductive age, 18-44 years old, at least 6 months past their last chemotherapy treatment., Interventions: Not applicable., Main Outcome Measures: Recall of details surrounding cancer diagnosis and chemotherapy regimens, recall of FP counseling and ovarian reserve testing, and rates of chart-documented FP counseling., Results: In total, 117 patients completed the survey, with 112 verified via chart review. When asked to report the chemotherapy regimen, 57% (64 of the 112) marked "I don't know/prefer not to say." Regarding FP, 80% (90 of the 112) denied being offered counseling. Of the 37 (33%) who had documented FP conversations, 13 (35%) did not recall mention of fertility. Only 2 of 8 patients with ovarian reserve testing recalled this being performed at their initial visit. Multivariable logistic regression revealed older age was significantly associated with not being offered FP (odds ratio [OR] 0.87)., Conclusions: Our results confirm that the accuracy of oncology patients' reporting is limited by a poor recall, particularly regarding their specific chemotherapy regimen. More than 1 in 3 patients documented to have been offered FP counseling do not recall this discussion. Importantly, only one-third of cancer survivors had chart-documented FP counseling. Increased efforts are needed to ensure adequate follow-up beyond the initial visit.

Community-acquired pneumonia (CAP) is the single largest infectious cause of hospitalization and death in children worldwide. With improved immunizations, the incidence of bacterial pneumonia and the number of colonized bacteria have decreased. However, respiratory viruses are still an important cause of CAP, especially as new infectious agents such severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. The SARS-CoV-2 virus emerged in 2019 and caused the current coronavirus disease 2019 pandemic. Therefore, it is necessary to elucidate the epidemiology and causative pathogens of CAP. Recently, the Pneumonia and Respiratory Disease Study Group, affiliated with the Korean Academy of Pediatric Allergy and Respiratory Disease, investigated the causative pathogens of respiratory infections in children hospitalized with CAP, the serotype of Streptococcus pneumoniae, and the prevalence of Mycoplasma pneumoniae with gene mutations. Antibiotic resistance and serotype test results can determine the use of empirical antibiotics. Moreover, it is possible to help develop future vaccines by comparing bacterial culture results with vaccine serotype and identifying the changes and prevalence of each serotype. Therefore, we will perform continuous national surveillance and monitor the epidemiology of respiratory pathogens in Korea and worldwide. The surveillance of these respiratory infections can play a role in monitoring the emergence of new infectious diseases such as SARS-CoV-2.

Although effort required to complete spirometry is known to differ by age, no studies have addressed this issue. The present study aimed to identify the difference in the effort required to complete spirometry by age in children and adolescents. Data from 707 children (mean age, 10.2 years; range, 4-25 years) from 6 medical centers were analyzed. In addition to demographics, we obtained information on the time required for as well as the number of demonstrations and spirometry demonstrations and trials from the patients' electronic medical records. A total of 398 (56.3%) male participants were included, and 300 (42.4%) participants had no prior experience receiving spirometry. The mean time required for spirometry demonstration was 2.7 minutes (standard deviation [SD], 2.1 minutes), whereas that for spirometry trial was 5.9 minutes (SD, 5.1 minutes). The total mean time required for spirometry was 8.6 minutes (SD, 6.5 minutes). Significant negative associations were observed between age and effort required to complete spirometry with respect to the time and number of demonstrations and trials. The results of the present study suggest that age may affect the degree of effort required to complete spirometry, with a pattern of increasing effort with decreasing age. This finding provides important evidence for the establishment of health care policies especially regarding lung diseases that can benefit from spirometry., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Introduction: Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children., Methods: A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay., Results: Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five., Conclusions: This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Pectobacterium atrosepticum ( P. atrosepticum : Pba ) which causes potato soft rot and blackleg is a notorious plant pathogen worldwide. Discovery of new types of antimicrobial chemicals that target specifically to virulence factors such as bacterial motility and extracellular enzymes is required for protecting crops from pathogenic infection. A transcriptomic analysis of Pba upon hopeaphenol treatment revealed that bacterial motility-related gene expression, including a master regulator flhDC genes, was significantly influenced by hopeaphenol. We further generated a double knock-out mutant of flhDC genes by CRISPR/Cas9 system and confirmed phenotypic changes in bacterial motility, transcription of extracellular enzymes, and disease development consistent with the result of wild-type treated with hopeaphenol. The hopeaphenol-treated Pba strains, wild-type, double mutant, and complemented strain were unable to secrete the enzymes in vitro , while Δ flhDC double mutant strain reduced the secretion. Thus, our study supports that FlhDC is essential for the virulence of Pba , and proposes that hopeaphenol modulates FlhDC-dependent virulence pathways, suggesting a potential of hopeaphenol as an anti-virulence agent to manage potato soft rot and blackleg diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang, Hwang, Yoo, Kim and Chung.)

Regular exercise that meets or exceeds the current physical activity guidelines is associated with a reduced risk of cardiovascular disease (CVD) and mortality. Therefore, exercise training plays an important role in primary and secondary prevention of CVD. In this part 1 of a 4-part focus seminar series, we highlight the mechanisms and physiological adaptations responsible for the cardioprotective effects of exercise. This includes an increase in cardiorespiratory fitness secondary to cardiac, vascular, and skeletal muscle adaptations and an improvement in traditional and nontraditional CVD risk factors by exercise training. This extends to the role of exercise and its prescription in patients with CVDs (eg, coronary artery disease, chronic heart failure, peripheral artery disease, or atrial fibrillation) with special focus on the optimal mode, dosage, duration, and intensity of exercise to reduce CVD risk and improve clinical outcomes in these patients., Competing Interests: Funding Support and Author Disclosures Dr Kovacic is the recipient of an Agilent Thought Leader Award (January 2022), which includes funding for research that is unrelated to the current paper; and has received research support from the National Institutes of Health (R01HL148167), New South Wales health grant RG194194, the Bourne Foundation, and Agilent. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: For optimal fertility testing, serum anti-Müllerian hormone levels are used in combination with other testing to provide reliable ovarian reserve evaluations. The use of the ADx 100 card is widely commercially available for at-home reproductive hormone testing, but data demonstrating that its results are reproducible outside of a clinical setting are limited, as well as comparisons of its performance with other newer blood collection techniques. This study aimed to evaluate the concordance of serum AMH levels found via standard venipuncture and self-administered blood collection using the TAP II device (TAP) and ADx card in women of reproductive age., Methods: This was a prospective, head-to-head-to-head within-person crossover comparison trial that included 41 women of reproductive age (20-39 years). It was hypothesized that the TAP device would be superior to the ADx card both in terms of agreement with venipuncture reference standard and patient experience. Each subject had their blood drawn using the three modalities (TAP, ADx, and venipuncture). We evaluated the concordance of AMH assays from samples obtained via the TAP device and ADx card with the gold standard being venipuncture. Two-sided 95% CIs were generated for each method to compare relative performance across all three modes. Patient preference for the TAP device versus the ADx card was based on self-reported pain and Net Promoter Score (NPS)., Results: The TAP device was superior to the ADx card on all outcome measures. TAP R-squared with venipuncture was 0.99 (95% CI 0.99, > 0.99), significantly higher than the ADx card, which had an R-squared of 0.87 (95% CI 0.80, 0.94) under most favorable treatment. TAP sensitivity and specificity were both 100% (no clinical disagreement with venipuncture), versus 100 and 88%, respectively, for the ADx card. Average pain reported by users of the TAP device was significantly lower than the ADx card (0.75 versus 2.73, p < 0.01) and the NPS was significantly higher than the ADx card (+ 72 versus - 48, p < 0.01)., Conclusions: The TAP was non-inferior to venipuncture and superior to the ADx card with respect to correlation and false positives. Moreover, the TAP was superior to both alternatives on patient experience., Trial Registration: NCT04784325 (Mar 5, 2021)., (© 2022. The Author(s).)

Objective: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year., Patients and Methods: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated., Results: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period., Conclusions: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Background: Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin B 12 in patients with rosacea., Objective: To investigate serum Hcy, vitamin B 12 , and folic acid levels in patients with papulopustular rosacea (PPR), we characterized the association of these levels with PPR severity., Methods: This case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin B 12 , and folic acid were measured. A correlation was assessed between disease severity and serum levels of Hcy, vitamin B 12 , and folic acid., Results: Serum vitamin B 12 and folic acid levels were significantly lower in PPR patients than in the healthy controls ( p = 0.011 and p = 0.0173, respectively). Although serum Hcy levels did not significantly differ between PPR patients and healthy controls, PPR severity was positively correlated with serum Hcy levels ( p < 0.001)., Conclusions: Our results suggest a possible association between hyperhomocysteinemia and vitamin B 12 deficiency in patients with PPR., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Bo Young Chung et al.)