Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is the prototypic genomic disorder resulting from deficiency of paternally expressed genes in the human chromosome 15q11-q13 region. The unique molecular mechanism involving epigenetic modifications renders PWS as the most attractive candidate to explore a proof-of-concept of epigenetic therapy in humans. The premise is that epigenetic modulations could reactivate the repressed PWS candidate genes from the maternal chromosome and offer therapeutic benefit. Our prior study identifies an EHMT2/G9a inhibitor, UNC0642, that reactivates the expression of PWS genes via reduction of H3K9me2. However, low brain permeability and poor oral bioavailability of UNC0642 preclude its advancement into translational studies in humans. In this study, a newly developed inhibitor, MS152, modified from the structure of UNC0642, has better brain penetration and greater potency and selectivity against EHMT2/G9a. MS152 reactivated maternally silenced PWS genes in PWS patient fibroblasts and in brain and liver tissues of PWS mouse models. Importantly, the molecular efficacy of oral administration is comparable with the intraperitoneal route. MS152 treatment in newborns ameliorates the perinatal lethality and poor growth, maintaining reactivation in a PWS mouse model at postnatal 90 days. Our findings provide strong support for MS152 as a first-in-class inhibitor to advance the epigenetic therapy of PWS in humans.

Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function.

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A2A receptor (A2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A2AR inhibition by the Food and Drug Administration-approved A2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin's antitumor activity. Collectively, our study identifies A2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.

Effect of tryptophan position and lysine/arginine substitution in antimicrobial peptides on antifungal action.

Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.

CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy.

Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy and have also been reported in families with only a cataract phenotype. Dilated cardiomyopathy (DCM) is a disorder with a highly heterogeneous genetic etiology involving more than 60 causative genes, hindering genetic diagnosis. In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in NM_001289808.2:c.527A>G of CRYAB in one patient. The mutant alpha-B crystallin protein is predicted to have an extended strand with addition of 19 amino acid residues, p.(Ter176TrpextTer19), which may contribute to aggregation and increased hydrophobicity of alpha-B crystallin. The proband, diagnosed with DCM at age 32, had a history of bilateral congenital cataracts but had no evidence of myopathy or associated symptoms. He also has a 10-year-old child diagnosed with bilateral congenital cataracts with the same CRYAB variant. This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies.

Impact of sulfur substitution on biotin binding affinity to streptavidin.

In this study, we investigated how the replacement of the tetrahydrothiophene ring of biotin with either an oxolane or (methyl)pyrrolidine moiety may affect its molecular interactions, in an effort to identify alternative affinity ligands suitable for in vitro and in vivo applications in synthetic biology. Initial molecular dynamics (MD) simulations suggested the potential formation of a hydrogen bond between either the oxygen or nitrogen atom of the envisaged tetrahydroheteryl analogues and the Thr90 residue of streptavidin, mirroring the sulfur-centered hydrogen bond detected by the crystallographic analysis of the biotin-streptavidin interaction. Therefore, oxy-, aza-, and N-methylazabiotin were readily synthesized starting from chiral five- or six-carbon sugar precursors. Based on fluorescence-based titration experiments using the corresponding fluorescein conjugates, oxybiotin showed a binding behavior similar to biotin with streptavidin, while both amino analogues displayed lower binding capacities. Notably, azabiotin exhibited a pH-dependent interaction profile, demonstrating enhanced binding under acidic conditions but weaker binding under basic pH, which could be exploited for various purposes.

Overcoming challenges associated with identifying FBN1 deep intronic variants through whole-genome sequencing.

BACKGROUND: Marfan syndrome (MFS), caused by pathogenic variants of FBN1 (fibrillin-1), is a systemic connective tissue disorder with variable phenotypes and treatment responsiveness depending on the variant. However, a significant number of individuals with MFS remain genetically unexplained. In this study, we report novel pathogenic intronic variants in FBN1 in two unrelated families with MFS. METHODS: We evaluated subjects with suspected MFS from two unrelated families using Sanger sequencing or multiplex ligation-dependent probe amplification of FBN1 and/or panel-based next-generation sequencing. As no pathogenic variants were identified, whole-genome sequencing was performed. Identified variants were analyzed by reverse transcription-PCR and targeted sequencing of FBN1 mRNA harvested from peripheral blood or skin fibroblasts obtained from affected probands. RESULTS: We found causative deep intronic variants, c.6163+1484A>T and c.5788+36C>A, in FBN1. The splicing analysis revealed an insertion of in-frame or out-of-frame intronic sequences of the FBN1 transcript predicted to alter function of calcium-binding epidermal growth factor protein domain. Family members carrying c.6163+1484A>T had high systemic scores including prominent skeletal features and aortic dissection with lesser aortic dilatation. Family members carrying c.5788+36C>A had more severe aortic root dilatation without aortic dissection. Both families had ectopia lentis. CONCLUSION: Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies. This study expands the mutation spectrum of FBN1 and points out the importance of intronic sequence analysis and the need for integrative functional studies in MFS diagnosis.

Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects. Nanoparticles (NPs) have extreme potential for enhancing therapeutic efficacy but require continued research to elucidate beneficial interventions for women cancer survivors. In short, nanotechnology-based approaches have emerged as promising strategies for preventing and treating chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy. NP-based drug delivery systems and therapeutics have shown potential for reducing the side effects of chemotherapeutics while improving drug efficacy. In this article, the latest nanotechnology approaches and their potential for the prevention and treatment of chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy in breast and ovarian cancer survivors are discussed.

Comparison of imaging findings of macrotrabecular-massive hepatocellular carcinoma using CT and gadoxetic acid-enhanced MRI.

OBJECTIVES: To investigate the imaging findings of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) on CT and MRI, and examine their diagnostic performance and prognostic significance. METHODS: We retrospectively enrolled 220 consecutive patients who underwent hepatic resection between June 2009 and December 2013 for single treatment-naïve HCC, who have preoperative CT and gadoxetic acid-enhanced MRI. Independent reviews of histopathology and imaging were performed by two reviewers. Previously reported imaging findings, LI-RADS category, and CT attenuation of MTM-HCC were investigated. The diagnostic performance of the MTM-HCC diagnostic criteria was compared across imaging modalities. RESULTS: MTM-HCC was associated with ≥ 50% arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin on CT and MRI (p < .05). Arterial phase hypovascular components were less commonly observed on MRI subtraction images than on CT or MRI, while non-rim arterial phase hyperenhancement and LR-5 were more commonly observed on MRI subtraction images than on MRI (p < .05). MTM-HCC showed lower tumor attenuation in the CT arterial phase (p = .01). Rhee's criteria, defined as ≥ 50% hypovascular component and ≥ 2 ancillary findings (intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin), showed similar diagnostic performance for MRI (sensitivity, 41%; specificity, 97%) and CT (sensitivity, 31%; specificity, 94%). Rhee's criteria on CT were independent prognostic factors for overall survival. CONCLUSION: The MRI diagnostic criteria for MTM-HCC are applicable on CT, showing similar diagnostic performance and prognostic significance. For MTM-HCC, arterial phase subtraction images can aid in the HCC diagnosis by depicting subtle arterial hypervascularity. KEY POINTS: • MTM-HCC on CT demonstrated previously described MRI findings, including arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and necrosis. • The MRI diagnostic criteria for MTM-HCC were also applicable to CT, showing comparable diagnostic performance and prognostic significance. • On arterial phase subtraction imaging, MTM-HCC more frequently demonstrated non-rim enhancement and LR-5 and less frequently LR-M than MRI arterial phase, which may aid in the diagnosis of HCC.

Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.

BACKGROUND: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. MATERIALS AND METHODS: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. RESULTS: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. CONCLUSION: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.

Fabrication, Structural Characteristics, and Properties of Sericin-Coated Wool Nonwoven Fabrics.

Recently, nonwoven fabrics from natural silk have attracted considerable attention for biomedical and cosmetic applications because of their good mechanical properties and cytocompatibility. Although these fabrics can be easily fabricated using the binding character of sericin, the high cost of silk material may restrict its industrial use in certain areas. In this study, sericin was added as a binder to a cheaper material (wool) to prepare wool-based nonwoven fabrics and investigate the effect of the amount of sericin added on the structural characteristics and properties of the wool nonwoven fabric. It was found using SEM that sericin coated the surface of wool fibers and filled the space between them. With an increase in sericin addition, the porosity, moisture regain, and the contact angle of the sericin-coated wool nonwoven fabric decreased. The maximum stress and initial Young's modulus of the nonwoven fabric increased with the increase in sericin amount up to 32.5%, and decreased with a further increase in the amount of sericin. Elongation at the end steadily decreased with the increase in sericin addition. All of the nonwoven fabrics showed good cytocompatibility, which increased with the amount of sericin added. These results indicate that sericin-coated wool-based nonwoven fabrics may be successfully prepared by adding sericin to wool fibers, and that the properties of these fabrics may be diversely controlled by altering the amount of sericin added, making them promising candidates for biomedical and cosmetic applications.

Fabrication, Structure, and Properties of Nonwoven Silk Fabrics Prepared with Different Cocoon Layers.

In this study, five different nonwoven silk fabrics were fabricated with silk fibers from different cocoon layers, and the effect of the cocoon layer on the structural characteristics and properties of the nonwoven silk fabric was examined. The diameter of the silk fiber and thickness of the nonwoven silk fabric decreased from the outer to the inner cocoon layer. More amino acids with higher hydrophilicity (serine, aspartic acid, and glutamic acid) and lower hydrophilicity (glycine and alanine) were observed in the outer layers. From the outer to the inner layer, the overall crystallinity and contact angle of the nonwoven silk fabric increased, whereas its yellowness index, moisture retention, and mechanical properties decreased. Regardless of the cocoon layer at which the fiber was sourced, the thermal stability of fibroin and sericin and good cell viability remained unchanged. The results of this study indicate that the properties of nonwoven silk fabric can be controlled by choosing silk fibers from the appropriate cocoon layers. Moreover, the findings in this study will increase the applicability of nonwoven silk fabric in the biomedical and cosmetic fields, which require specific properties for industrialization.

The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Natural Cyclophilin A Inhibitors Suppress the Growth of Cancer Stem Cells in Non-Small Cell Lung Cancer by Disrupting Crosstalk between CypA/CD147 and EGFR.

Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and progression, treatment resistance, and NSCLC recurrence. Therefore, the development of novel therapeutic targets and anticancer drugs that effectively block CSC growth may improve treatment outcomes in patients with NSCLC. In this study, we evaluated, for the first time, the effects of natural cyclophilin A (CypA) inhibitors, including 23-demethyl 8,13-deoxynargenicin (C9) and cyclosporin A (CsA), on the growth of NSCLC CSCs. C9 and CsA more sensitively inhibited the proliferation of epidermal growth factor receptor (EGFR)-mutant NSCLC CSCs than EGFR wild-type NSCLC CSCs. Both compounds suppressed the self-renewal ability of NSCLC CSCs and NSCLC-CSC-derived tumor growth in vivo. Furthermore, C9 and CsA inhibited NSCLC CSC growth by activating the intrinsic apoptotic pathway. Notably, C9 and CsA reduced the expression levels of major CSC markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2, through dual downregulation of the CypA/CD147 axis and EGFR activity in NSCLC CSCs. Our results also show that the EGFR tyrosine kinase inhibitor afatinib inactivated EGFR and decreased the expression levels of CypA and CD147 in NSCLC CSCs, suggesting close crosstalk between the CypA/CD147 and EGFR pathways in regulating NSCLC CSC growth. In addition, combined treatment with afatinib and C9 or CsA more potently inhibited the growth of EGFR-mutant NSCLC CSCs than single-compound treatments. These findings suggest that the natural CypA inhibitors C9 and CsA are potential anticancer agents that suppress the growth of EGFR-mutant NSCLC CSCs, either as monotherapy or in combination with afatinib, by interfering with the crosstalk between CypA/CD147 and EGFR.

Production of Plant-Derived Japanese Encephalitis Virus Multi-Epitope Peptide in Nicotiana benthamiana and Immunological Response in Mice.

The current production of the Japanese encephalitis virus (JEV) vaccine is based on animal cells, where various risk factors for human health should be resolved. This study used a transient expression system to express the chimeric protein composed of antigenic epitopes from the JEV envelope (E) protein in Nicotiana benthamiana. JEV multi-epitope peptide (MEP) sequences fused with FLAG-tag or 6× His-tag at the C- or N-terminus for the purification were introduced into plant expression vectors and used for transient expression. Among the constructs, vector pSK480, which expresses MEP fused with a FLAG-tag at the C-terminus, showed the highest level of expression and yield in purification. Optimization of transient expression procedures further improved the target protein yield. The purified MEP protein was applied to an ICR mouse and successfully induced an antibody against JEV, which demonstrates the potential of the plant-produced JEV MEP as an alternative vaccine candidate.

Concept analysis of adolescent use of social media for emotional well-being.

AIM: The aim of the study is to conduct a concept analysis of adolescents' emotional well-being resulting from healthy social media use. BACKGROUND: Adolescents are the group that uses mobile social media the most. They connect to others and achieve life satisfaction via social media. Here, we consider both the positive and negative aspects of social media use and recognize the need for clear guidance on proper social media use among adolescents. DESIGN: This study utilized an eight-step method of concept analysis. DATA SOURCES: A systematic literature search of PubMed, CINAHL and PsycInfo was conducted, and 10 articles were selected. REVIEW METHODS: We defined attributes, model cases, antecedents, consequences and referents. RESULTS: The attributes of adolescent emotional well-being on social media are (a) relationships with others, (b) internet-based communication and (c) being happy and maintaining emotional health. Adolescents use social media to feel safe, seek information and connect to others. Adolescents reported having better relationships and positive affect as a result of social media use. CONCLUSION: This concept analysis will help health-care providers understand how adolescent emotional well-being is attained through social media. Additionally, this study will provide the basis of behavioural theories and future interventions that guide adolescent use of social media.

Molecular Characterization of Biliary Tract Cancer Predicts Chemotherapy and Programmed Death 1/Programmed Death-Ligand 1 Blockade Responses.

BACKGROUND AND AIMS: Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS: We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS: This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.

Control of a nosocomial measles outbreak among previously vaccinated adults in a population with high vaccine coverage: Korea, 2019.

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.

Effects of a new respiratory muscle training device in community-dwelling elderly men: an open-label, randomized, non-inferiority trial.

BACKGROUND: Respiratory muscle training (RMT) has various clinical benefits in older adults; however, the low adherence to training remains a challenging issue. The present study aimed to confirm the efficacy of a new device that combines inspiratory muscle training and a positive expiratory pressure (IMT/PEP) compared to that of a Threshold IMT device (Philips Respironics Inc), and to determine whether home-based training differed from rehabilitation center training. METHODS: This four-arm, multicenter, parallel, non-inferiority trial randomized 80 active community-dwelling older men (mean age = 72.93 ± 5.02 years) to center-based groups (new IMT/PEP device or Threshold IMT device; 16 supervised sessions) or home-based groups (new IMT/PEP device or Threshold IMT device; 2 supervised sessions and individual sessions). Participants in all groups performed RMT twice a day for 8 weeks. Assessments were performed at baseline and post-training. The primary outcomes were maximum inspiratory pressure and maximal expiratory pressure. The secondary outcomes included forced vital capacity and forced expiratory volume in the first second, peak cough flow, diaphragm thickness, VO2 peak, the International Physical Activity Questionnaire score, electromyographic activities of the sternocleidomastoid muscle, and skeletal muscle mass and phase angle as measured by bioimpedance analysis. In addition, rates of adherence to each protocol were also compared. RESULTS: Among all groups, the maximal inspiratory pressure was improved post-training, while the maximal expiratory pressure showed improvement only in the IMT/PEP groups. The overall non-inferiority of the IMT/PEP device was thus validated. A statistically significant improvement in diaphragm thickness was found. However, no consistent improvement was shown in other secondary outcomes. No significant difference in training adherence rate between protocols was observed (mean adherence rate of 91-99%). CONCLUSION: Compared to the Threshold IMT, the new IMT/PEP device did not result in a significant difference in maximal inspiratory pressure but did improve maximal expiratory pressure in older men. The IMT/PEP device's improved usability, which is associated with exercise adherence, provided distinct advantages in this cohort. If proper education is first provided, home-based RMT alone may provide sufficient effects in older individuals. TRIAL REGISTRATION: This trial was registered in the database cris.nih.go.kr (registration number KCT0003901 ) on 10/05/2019.