Seasonal Stability Assessment of Reference Genes for Quantitative Real-Time Polymerase Chain Reaction Normalization in Bombus terrestris.

Bumblebees (B. terrestris) play a crucial role as highly efficient biological agents in commercial pollination. Understanding the molecular mechanisms governing their adaptation to diverse seasonal environments may pave the way for effective management strategies in the future. With the burgeoning advancement in post-genetic studies focusing on B. terrestris, there is a critical need to normalize quantitative real-time PCR (qRT-PCR) data using suitable reference genes. To address this necessity, we employed RefFinder, a software-based tool, to assess the suitability of several candidate endogenous control genes, including actin (ACT), arginine kinase (AK), elongation factor 1 alpha (EF1), glyceraldehyde-3-phosphate (GAPDH), phospholipase (PLA2), and ribosomal proteins (S18, S28). These genes were evaluated for their efficacy as biological endogenous controls by examining their expression patterns across various environmental conditions corresponding to different seasons (Spring, Summer, Autumn, Winter) and tissues (ovary, fat body, thorax, head) in bumblebees. Moreover, the study investigated the significance of selecting appropriate reference genes for three key genes involved in the juvenile hormone (JH) signaling pathways: Krüppel homolog 1 (Kr-h1), methyl farnesoate epoxidase (MFE), and Vitellogenin (Vg). Our research identifies specific genes suitable for normalization in B. terrestris, thereby offering valuable insights into gene expression and functional metabolic genetics under varying seasonal conditions. This catalog of reference genes will serve as a valuable resource for future research endeavors.

Structural and biochemical analysis of the unique interactions of the Campylobacter jejuni CorA channel protein with divalent cations.

CorA is a Mg2+ channel that plays a key role in the homeostasis of intracellular Mg2+ in bacteria and archaea. CorA consists of a cytoplasmic domain and a transmembrane domain and generates a Mg2+ pathway by forming a pentamer in the cell membrane. CorA gating is regulated via negative feedback by Mg2+, which is accommodated by the pentamerization interface of the CorA cytoplasmic domain (CorACD). The Mg2+-binding sites of CorACD differ depending on the species, suggesting that the Mg2+-binding modes and Mg2+-mediated gating mechanisms of CorA vary across prokaryotes. To define the Mg2+-binding mechanism of CorA in the Campylobacter jejuni pathogen, we structurally and biochemically characterized C. jejuni CorACD (cjCorACD). cjCorACD adopts a three-layered α/ß/α structure as observed in other CorA orthologs. Interestingly, cjCorACD exhibited enhanced thermostability in the presence of Ca2+, Ni2+, Zn2+, or Mn2+ in addition to Mg2+, indicating that cjCorACD interacts with diverse divalent cations. This cjCorACD stabilization is mediated by divalent cation accommodation by negatively charged residues located at the bottom of the cjCorACD structure away from the pentamerization interface. Consistently, cjCorACD exists as a monomer irrespective of the presence of divalent cations. We concluded that cjCorACD binds divalent cations in a unique pentamerization-independent manner.

Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains.

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia. P-BdECM composition is comparable to human BdECM regarding brain-specificity through the matrisome and gene ontology-biological process analysis. As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM. Annexin A1(ANXA1) and Peroxiredoxin(PRDX) in P-BdECM stabilized microglial and astrocytic behavior under normal while promoting active neuroinflammation in response to neuropathological factors. Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study.

Alteration of γδ T cell subsets in non-human primates transplanted with GGTA1 gene-deficient porcine blood vessels.

BACKGROUND: αGal-deficient xenografts are protected from hyperacute rejection during xenotransplantation but are still rejected more rapidly than allografts. Despite studies showing the roles of non-Gal antibodies and αß T cells in xenograft rejection, the involvement of γδ T cells in xenograft rejection has been limitedly investigated. METHODS: Six male cynomolgus monkeys were transplanted with porcine vessel xenografts from wild-type (n = 3) or GGTA1 knockout (n = 3) pigs. We measured the proportions and T cell receptor (TCR) repertoires of blood γδ T cells before and after xenotransplant. Grafted porcine vessel-infiltrating immune cells were visualized at the end of experiments. RESULTS: Blood γδ T cells expanded and infiltrated into the graft vessel adventitia following xenotransplantation of α-Gal-deficient pig blood vessels. Pre- and post-transplant analysis of γδ TCR repertoire revealed a transition in δ chain usage post-transplantation, with the expansion of several clonotypes of δ1, δ3, or δ7 chains. Furthermore, the distinctions between pre- and post-transplant δ chain usages were more prominent than those observed for γ chain usages. CONCLUSION: γδ TCR repertoire was significantly altered by xenotransplantation, suggesting the role of γδ T cells in sustained xenoreactive immune responses.

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease.

PURPOSE: To identify associations between computed tomography (CT)-based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD). MATERIALS AND METHODS: In a mixed retrospective and prospective cohort study, 139 patients without prior lower-extremity intervention who underwent CT angiography of the aorta and lower extremities were identified. Subjects were classified as asymptomatic, claudicants, or having chronic limb-threatening ischemia (CLTI). LECS was measured using the Agatston method. Univariate and multivariate analyses were performed across categories of PAD severity. Receiver operating characteristic (ROC) analysis was performed, and an optimal cutoff point for LECS was identified. Claudicants were followed prospectively for CLTI and mortality. RESULTS: Higher infrapopliteal calcium score (CS) was independently associated with CLTI versus claudication (odds ratio [OR], 3.24 per unit increase in log10-transformed CS; P < .001) in addition to hemodialysis dependence and poor functional status. One hundred eighty-eight Agatston units was identified as the optimal cutoff for infrapopliteal CS in assessing the risk of CLTI versus claudication (area under the ROC curve, 0.84 [SD ± 0.049]). This cutoff was validated in an independent cohort to be associated with progression to CLTI (OR, 12.8; P = .0039). In the claudicant group followed prospectively, infrapopliteal CS ≥188 predicted increased risk of CLTI or death after adjusting for functional status and hemodialysis dependence (Cox hazard ratio, 4.92; P = .0202). CONCLUSIONS: Higher infrapopliteal CS was associated with CLTI among those with symptomatic PAD. An infrapopliteal CS cutoff of 188 Agatston units may serve as a useful tool to identify patients with increased risk of CLTI and mortality.

Interaction between healthcare providers and parents of children or adolescents with epilepsy: A qualitative systematic review and meta-synthesis.

AIMS: This study aimed to explore the interactions between healthcare providers and parents of children or adolescents with epilepsy. A qualitative systematic review based on the theory-generating meta-synthesis research approach proposed by Finfgeld-Connett (2018) was applied. MATERIALS AND METHODS: We searched for empirical qualitative studies in five electronic databases (PubMed, Embase, CINAHL, Cochrane Library, and Web of Science), from January 1, 2003 to February 9, 2023. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to guide the selection process, and two researchers independently assessed the methodological quality of the articles using the Critical Appraisal Skills Programme Qualitative Studies Checklist. RESULTS: Of the 4,768 studies initially imported for screening, 27 studies were reviewed and synthesized. Only one qualitative study directly focused on the interactions between parents and healthcare providers, but various studies mentioning such interaction as themes or sub-themes of other phenomena allowed us to draw out common attributes. Defining attribute, "journey through the three stages of interaction," were derived as follows: Stage 1: trust vs. mistrust; Stage 2: autonomy vs. doubt; Stage 3: adaptation. The antecedents included encounters with healthcare providers and parent empowerment. A patient-centered approach was found to be the consequence. CONCLUSION: It is important for parents of children or adolescents with epilepsy to empower themselves and increase their interactions. Considering the stage of interaction, healthcare providers and researchers should explore strategies to promote effective communication. Further research is required to develop strategies aimed at supporting parents and healthcare providers to achieve the tasks at each stage and maintain Stage 3, "adaptation."

CRISPR/Cas9-mediated knockout of scarlet gene produces eye color mutants in the soybean looper, Chrysodeixis includens.

The CRISPR/Cas9 technology has greatly progressed research on non-model organisms, demonstrating successful applications in genome editing for various insects. However, its utilization in the case of the soybean looper, Chrysodeixis includens, a notable pest affecting soybean crops, has not been explored due to constraints such as limited genomic information and the embryonic microinjection technique. This study presents successful outcomes in generating heritable knockout mutants for a pigment transporter gene, scarlet, in C. includens through CRISPR/Cas9-mediated mutagenesis. The scarlet locus identified in the genome assembly of C. includens consists of 14 exons, with a coding sequence extending for 1,986 bp. Two single guide RNAs (sgRNAs) were designed to target the first exon of scarlet. Microinjection of these two sgRNAs along with the Cas9 protein into fresh embryos resulted in the successful production of variable phenotypes, particularly mutant eyes. The observed mutation rate accounted for about 16%. Genotype analysis revealed diverse indel mutations at the target site, presumably originating from double-strand breaks followed by the nonhomologous end joining repair, leading to a premature stop codon due to frame shift. Single-pair mating of the mutant moths produced G1 offspring, and the establishment of a homozygous mutant strain occurred in G2. The mutant moths exhibited lightly greenish or yellowish compound eyes in both sexes, confirming the involvement of scarlet in pigmentation in C. includens. Notably, the CRISPR/Cas9-mediated genome editing technique serves as a visible phenotypic marker, demonstrating its proof-of-concept applicability in C. includens, as other pigment transporter genes have been utilized as visible markers to establish genetic control for various insects. These results provide the first successful case that the CRISPR/Cas9 method effectively induces mutations in C. includes, an economically important soybean insect pest.

A comparison of factors associated with unmet healthcare needs in people with disabilities before and after COVID-19: a nationally representative population-based study.

BACKGROUND: People with disabilities, who require numerous healthcare services, are vulnerable to unmet healthcare needs. This study aimed to investigate and identify the factors that influence unmet healthcare needs among people with disabilities and to compare these factors before and after the COVID-19 pandemic in South Korea. METHODS: A propensity score matching analysis was conducted using two datasets from the National Survey of Disabled Persons collected in 2017 and 2020. The participants were matched based on variables known to influence healthcare utilization. Based on the Andersen model, logistic regression was performed to analyze the key characteristics of the factors associated with unmet healthcare needs, including predisposing, enabling, and need factors. RESULTS: Propensity score matching resulted in the inclusion of 1,884 participants in each group: an experimental group and control group. Before COVID-19, factors associated with unmet healthcare needs included sex, age, marital status, and education level (predisposing factors), instrumental activities of daily living dependency, satisfaction with medical staff's understanding of disability, satisfaction with medical institutional facilities and equipment (enabling factors), subjective health status, and depressive symptoms (need factors). After COVID-19, factors included physical disability, instrumental activities of daily living dependency, and discrimination (enabling factors), and subjective health status, chronic diseases, depressive symptoms, and regular medical care (need factors). No significant predisposing factors affecting unmet healthcare needs were identified after COVID-19. CONCLUSIONS: This study compared the factors affecting unmet healthcare needs among people with disabilities before and after COVID-19. Recognizing the different factors associated with unmet healthcare needs before and after COVID-19, (e.g., sex, type of disability, satisfaction with medical staff's understanding of disabilities, medical institutional facilities and equipment considering the disabled, discrimination, chronic diseases, and regular medical care) may help governments and policymakers establish strategies to reduce and prevent unmet healthcare needs during and a future crisis.

Congruency and its related factors between patients' fall risk perception and nurses' fall risk assessment in acute care hospitals.

INTRODUCTION: Inpatients need to recognize their fall risk accurately and objectively. Nurses need to assess how patients perceive their fall risk and identify the factors that influence patients' fall risk perception. PURPOSE: This study aims to explore the congruency between nurses' fall risk assessment and patients' perception of fall risk and identify factors related to the non-congruency of fall risk. DESIGNS: A descriptive and cross-sectional design was used. The study enrolled 386 patients who were admitted to an acute care hospital. Six nurses assessed the participants' fall risk. Congruency was classified using the Morse Fall Scale for nurses and the Fall Risk Perception Questionnaire for patients. FINDINGS: The nurses' fall risk assessments and patients' fall risk perceptions were congruent in 57% of the participants. Underestimation of the patient's risk of falling was associated with gender (women), long hospitalization period, department (orthopedics), low fall efficacy, and history of falls before hospitalization. Overestimation of fall risk was associated with age group, gender (men), department, and a high health literacy score. In the multiple logistic regression, the factors related to the underestimation of fall risk were hospitalization period and department, and the factors related to the overestimation of fall risk were health literacy and department. CONCLUSIONS: Nurses should consider the patient's perception of fall risk and incorporate it into fall prevention interventions. CLINICAL RELEVANCE: Nurses need to evaluate whether patients perceive the risk of falling consistently. For patients who underestimate or overestimate their fall risk, it may be helpful to consider clinical and fall-related characteristics together when evaluating their perception of fall risk.

The Use of Telehealth for People With Disabilities: A Systematic Literature Review and Narrative Synthesis.

AIMS: To identify the use of telehealth for people with disabilities in community or primary care settings and to explore effective telehealth interventions for this group. DESIGN: Systematic literature review and narrative synthesis. DATA SOURCES: The literature search was conducted in January 2024 using five electronic databases including PubMed, EMBASE, CINAHL, Cochrane library and PsycINFO. METHODS: The review followed the Tawfik's guideline and adhered to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines for reporting. Out of 7363 retrieved articles, 1871 duplicates were removed, 5389 were excluded after title and abstract review, and 4 were excluded due to unavailable full text. One additional article was obtained through citation and hand searching. Thirteen studies were quality assessed using the Mixed Methods Appraisal Tool. Quantitative data were narratively synthesised. RESULTS: Thirteen quantitative studies were selected including three quasi-experimental studies and ten randomised controlled trials. The types of telehealth included telemonitoring, computerised intervention, virtual reality, telephone care, mHealth tools, decision support tools, digital storytelling and technology-assisted language interventions. The most common type of disability was intellectual disability, and the most common telehealth provider was the digital device itself. Most studies used surveys as the data collection method and the interventions were mostly conducted individually. Computer-based telehealth interventions demonstrated significant improvement in attention, health knowledge and psychological well-being. Telephone, virtual reality and tablet interventions also had positive impacts on body weight, motor coordination and pragmatic language skills. Telemonitoring was also beneficial. CONCLUSIONS: This systematic review examined the current state and effectiveness of telehealth interventions for people with disabilities. However, few intervention studies were found, and some studies were of poor quality. Continued interest and efforts from the government and researchers are needed targeting people with disabilities. IMPACT: Results provide valuable insights for healthcare providers, policymakers and researchers. They raise awareness about the potential of telehealth to address healthcare disparities and improve access to care for people with disabilities. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution: Systematic review.

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.

Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.

Correlation with Apoptosis Process through RNA-Seq Data Analysis of Hep3B Hepatocellular Carcinoma Cells Treated with Glehnia littoralis Extract (GLE).

Glehnia littoralis is a perennial herb found in coastal sand dunes throughout East Asia. This herb has been reported to have hepatoprotective, immunomodulatory, antioxidant, antibacterial, antifungal, anti-inflammatory, and anticancer activities. It may be effective against hepatocellular carcinoma (HCC). However, whether this has been proven through gene-level RNA-seq analysis is still being determined. Therefore, we are attempting to identify target genes for the cell death process by analyzing the transcriptome of Hep3B cells among HCC treated with GLE (Glehnia littoralis extract) using RNA-seq. Hep3B was used for the GLE treatment, and the MTT test was performed. Hep3B was then treated with GLE at a set concentration of 300 µg/mL and stored for 24 h, followed by RNA isolation and sequencing. We then used the data to create a plot. As a result of the MTT analysis, cell death was observed when Hep3B cells were treated with GLE, and the IC50 was about 300 µg/mL. As a result of making plots using the RNA-seq data of Hep3B treated with 300 µg/mL GLE, a tendency for the apoptotic process was found. Flow cytometry and annexin V/propidium iodide (PI) staining verified the apoptosis of HEP3B cells treated with GLE. Therefore, an increase or decrease in the DEGs involved in the apoptosis process was confirmed. The top five genes increased were GADD45B, DDIT3, GADD45G, CHAC1, and PPP1R15A. The bottom five genes decreased were SGK1, CX3CL1, ZC3H12A, IER3, and HNF1A. In summary, we investigated the RNA-seq dataset of GLE to identify potential targets that may be involved in the apoptotic process in HCC. These goals may aid in the identification and management of HCC.

Effects of stress on burnout among infection control nurses during the COVID-19 pandemic: the mediating effects of social support and self-efficacy.

BACKGROUND: This study investigated the mediating effects of self-efficacy and social support on the relationship between stress and burnout among infection control nurses (ICNs) during an emerging infectious disease pandemic. METHODS: The study participants encompassed 210 ICNs with at least six months' experience in an infection control unit at a general hospital in South Korea during the COVID-19 pandemic. Data were analyzed using independent t-tests or one-way analysis of variance (ANOVA), while descriptive statistics were performed using SPSS/WIN 26.0 software. Hayes's PROCESS macro 4.2 software was used to verify the significance of the indirect effects of the mediators. RESULTS: Stress had a significant positive effect on burnout (ß = 0.80, p < .001), accounting for 73% of the variance. Self-efficacy (ß = - 0.26, p < .001) and social support (ß = - 0.11, p = .034) had a significant negative effect on burnout, accounting for 78% of the variance. Stress was lower when self-efficacy and social support were entered into the model (ß = 0.80 → 0.59), indicating that self-efficacy and social support mediated the relationship between stress and burnout. CONCLUSION: This study is significant in that it confirms the effects of self-efficacy and social support on the relationship between stress and burnout among ICNs. The results highlight the importance of establishing organizational support systems and developing and implementing programs for enhancing self-efficacy in order to reduce burnout among ICNs.

Collaborative project-based learning in global health: Enhancing competencies and skills for undergraduate nursing students.

BACKGROUND: Despite the importance of collaboration and communication in global health, existing educational approaches often rely on traditional one-way instruction from instructor to student. Therefore, this study aimed to evaluate the effectiveness of a newly developed undergraduate curriculum on global health in enhancing nursing students' competencies in global health and communication, problem-solving, and self-directed learning skills. METHODS: A 15-week course "Global Health and Nursing" was designed for undergraduate nursing students, and a collaborative project-based learning method was used. Study participants were undergraduate nursing students enrolled in the course. The study was a multi-method study and included quantitative and qualitative components. It employed a one-group pretest-posttest design to quantitatively assess the impact of the curriculum. Additionally, student experiences with the learning process were qualitatively explored through a focus group interview. A total of 28 students participated in this study, and 5 of them participated in the focus group interview. RESULTS: The collaborative project-based learning method significantly improved global health competency (t = - 10.646, df = 22, p < 0.001), with a large effect size. It also improved communication skills (t = - 2.649, df = 22, p = 0.015), problem-solving skills (t = - 3.453, df = 22, p = 0.002), and self-directed learning skills (t = - 2.375, df = 22, p = 0.027). Three themes were found through the focus group interview: (a) Promoting global health competency; (b) Fostering life skills through collaborative projects; and (c) Recommendations for future classes. The focus group interview indicated that overall, the study participants were satisfied with the collaborative project-based method for global health education. CONCLUSIONS: This study confirms that project-based learning significantly boosts the competencies and skills of students, recommending its broader adoption in nursing education. Nursing instructors should consider adopting this teaching approach for global health education at the undergraduate level. Future studies may employ a longitudinal design to assess the prolonged effects of the collaborative project-based learning approach, particularly focusing on the long-term retention of skills and the broader applicability of this model across different educational settings.

Association between Frailty and Asthma.

Background and Objectives: This study investigated whether there is an association between elderly frailty and asthma. Material Methods: We examined 9745 elderly participants who did not have asthma and 275 elderly patients who had asthma diagnosed by a doctor from the 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons Survey. Study Selections: The Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale was used to determine their level of frailty. The relationship between frailty and geriatric asthma was examined using multiple logistic regression analysis, which was adjusted for a number of confounding variables (socioeconomic, health behavior, psychological characteristics, and functional status). Results: Frailty as defined by the K-FRAIL scale was significantly higher in the asthma group (7.6%) than the non-asthma group (4.9%). The frailty phenotype component showed that resistance, ambulation, and illness severity were more severe in the asthma group than the non-asthma group. After adjusting, asthma was significantly associated with an increased risk of frailty (OR 1.45; 95% confidence interval [CI] 1.01-2.09) compared to the non-asthma group. Conclusions: Frailty might be associated with elderly asthma in patients from the Korean population. Frailty may not only be associated with asthma, but also with other diseases. So, more evidence is needed to establish this association.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.

Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus in vitro, intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases.

Reassuring Intraoperative Parameters Do Not Obviate the Need for Infrainguinal Bypass Completion Angiograms.

OBJECTIVE: To determine if routine completion angiography for lower extremity bypasses using vein conduit results in lower rates of postoperative bypass occlusion. SUMMARY OF BACKGROUND DATA: With the increasing availability of on-table angiography and significant advancements in endovascular techniques, some operators routinely perform completion angiograms. The effect of this surgical paradigm has yet to be rigorously compared to the more widespread selective use of completion imaging in the modern era. METHODS: This retrospective cohort study included infrainguinal arterial bypass procedures utilizing vein conduit completed at a single hospital system from 2001 to 2018 and compared postoperative outcomes between bypasses that underwent routine completion angiography versus selective completion angiography. Notably, any bypasses that underwent completion angiography due to intraoperative concerns were excluded from this analysis. RESULTS: 666 bypasses that were performed in 589 patients met inclusion criteria. 126 (16.9%) bypasses were classified into the routine completion angiogram group compared to 540 (81.0%) into the selective completion angiogram group. Patients who underwent routine completion angiograms had a rate of intraoperative reintervention of 22.2%. The routine angiogram group had lower rates of reintervention (3.9% vs 10.0%, P = 0.03) and graft occlusion (2.3% vs 9.2%, P = 0.01) at 1-month postoperatively. CONCLUSION: Lower extremity bypasses using vein conduit that undergo routine completion angiography are associated with lower rates of graft occlusion at 30-days postoperatively. Completion angiography should thus be routinely performed in infrainguinal bypasses that utilize venous conduit.

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV-A or RV-C types using log-linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV-A versus RV-C nAb responses. Our models identified limited reciprocal cross-neutralizing relationships for RV-A (A12-A75, A12-A78, A20-A78, and A75-A78) and only one for RV-C (C2-C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV-C2. Mixed-effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV-A and RV-C illnesses induced nAb responses of similar duration. These results indicate that both RV-A and RV-C nAb responses have only modest cross-reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV-C species may include even fewer cross-neutralizing types than RV-A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.

The metabolic contribution of SKN-1/Nrf2 to the lifespan of Caenorhabditis elegans.

BACKGROUND AND AIMS: SKN-1, a C. elegans transcription factor analogous to the mammalian NF-E2-related factor (Nrf2), has been known to promote oxidative stress resistance aiding nematodes' longevity. Although SKN-1's functions suggest its implication in lifespan modulation through cellular metabolism, the actual mechanism of how metabolic rearrangements contribute to SKN-1's lifespan modulation has yet to be well characterized. Therefore, we performed the metabolomic profiling of the short-lived skn-1-knockdown C. elegans. METHODS: We analyzed the metabolic profile of the skn-1-knockdown worms with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS) and obtained distinctive metabolomic profiles compared to WT worms. We further extended our study with gene expression analysis to examine the expression level of genes encoding all metabolic enzymes. RESULTS: A significant increase in the phosphocholine and AMP/ATP ratio, potential biomarkers of aging, was observed, accompanied by a decrease in the transsulfuration metabolites, NADPH/NADP+ ratio, and total glutathione (GSHt), which are known to be involved in oxidative stress defense. skn-1-RNAi worms also exhibited an impairment in the phase II detoxification system, confirmed by the lower conversion rate of paracetamol to paracetamol-glutathione. By further examining the transcriptomic profile, we found a decrease in the expression of cbl-1, gpx, T25B9.9, ugt, and gst, which are involved in GSHt and NADPH synthesis as well as in the phase II detoxification system. CONCLUSION: Our multi-omics results consistently revealed that the cytoprotective mechanisms, including cellular redox reactions and xenobiotic detoxification system, contribute to the roles of SKN-1/Nrf2 in the lifespan of worms.