Prevalence, Diagnostic Utility and Associated Characteristics of Bronchodilator Responsiveness.

Rationale: The prevalence and diagnostic utility of bronchodilator responsiveness (BDR) in a real-life setting is unclear. Objective: To explore this uncertainty in patients aged ⩾12 years with physician-assigned diagnoses of asthma, asthma and chronic obstructive pulmonary disease (COPD), or COPD in NOVELTY, a prospective cohort study in primary and secondary care in 18 countries. Methods: The proportion of patients with a positive BDR test in each diagnostic category was calculated using 2005 (ΔFEV1 or ΔFVC ⩾12% and ⩾200 ml) and 2021 (ΔFEV1 or ΔFVC >10% predicted) European Respiratory Society/American Thoracic Society criteria. Measurements and Main Results: We studied 3,519 patients with a physician-assigned diagnosis of asthma, 833 with a diagnosis of asthma + COPD, and 2,436 with a diagnosis of COPD. The prevalence of BDR was 19.7% (asthma), 29.6% (asthma + COPD), and 24.7% (COPD) using 2005 criteria and 18.1%, 23.3%, and 18.0%, respectively, using 2021 criteria. Using 2021 criteria in patients diagnosed with asthma, BDR was associated with higher fractional exhaled nitric oxide; lower lung function; higher symptom burden; more frequent hospital admissions; and greater use of triple therapy, oral corticosteroids, or biologics. In patients diagnosed with COPD, BDR (2021) was associated with lower lung function and higher symptom burden. Conclusions: BDR prevalence in patients with chronic airway diseases receiving treatment ranges from 18% to 30%, being modestly lower with the 2021 than with the 2005 European Respiratory Society/American Thoracic Society criteria, and it is associated with lower lung function and greater symptom burden. These observations question the validity of BDR as a key diagnostic tool for asthma managed in clinical practice or as a standard inclusion criterion for clinical trials of asthma and instead suggest that BDR be considered a treatable trait for chronic airway disease.

Evaluating the Classification Accuracy of Expression Quantitative Trait Loci Calculated Polygenic Risk Scores in Alzheimer's Disease.

Polygenic risk scores (PRS) hold promise for the early identification of those at risk from neurodegenerative disorders such as Alzheimer's Disease (AD), allowing for intervention to occur prior to neuronal damage. The current selection of informative single nucleotide polymorphisms (SNPs) to generate the risk scores is based on the modelling of large genome-wide association data using significance thresholds. However, the biological relevance of these SNPs is largely unknown. This study, in contrast, aims to identify SNPs with biological relevance to AD and then assess them for their ability to accurately classify cases and controls. Samples selected from the Brains for Dementia Research (BDR) were used to produce gene expression data to identify potential expression quantitative trait loci (eQTLs) relevant to AD. These SNPs were then incorporated into a PRS model to classify AD and controls in the full BDR cohort. Models derived from these eQTLs demonstrate modest classification potential with an accuracy between 61% and 67%. Although the model accuracy is not as high as some values in the literature based on significance thresholds from genome-wide association studies, these models may reflect a more biologically relevant model, which may provide novel targets for therapeutic intervention.

Deep Learning Models for Classification of Dental Diseases Using Orthopantomography X-ray OPG Images.

The teeth are the most challenging material to work with in the human body. Existing methods for detecting teeth problems are characterised by low efficiency, the complexity of the experiential operation, and a higher level of user intervention. Older oral disease detection approaches were manual, time-consuming, and required a dentist to examine and evaluate the disease. To address these concerns, we propose a novel approach for detecting and classifying the four most common teeth problems: cavities, root canals, dental crowns, and broken-down root canals, based on the deep learning model. In this study, we apply the YOLOv3 deep learning model to develop an automated tool capable of diagnosing and classifying dental abnormalities, such as dental panoramic X-ray images (OPG). Due to the lack of dental disease datasets, we created the Dental X-rays dataset to detect and classify these diseases. The size of datasets used after augmentation was 1200 images. The dataset comprises dental panoramic images with dental disorders such as cavities, root canals, BDR, dental crowns, and so on. The dataset was divided into 70% training and 30% testing images. The trained model YOLOv3 was evaluated on test images after training. The experiments demonstrated that the proposed model achieved 99.33% accuracy and performed better than the existing state-of-the-art models in terms of accuracy and universality if we used our datasets on other models.

Design and Analysis of Super Wideband Antenna for Microwave Applications.

In this article, a compact concentric structured monopole patch antenna for super wideband (SWB) application is proposed and investigated. The essential characteristics of the designed antenna are: (i) to attain super-wide bandwidth characteristics, the proposed antenna is emerged from a traditional circular monopole antenna and has obtained an impedance bandwidth of 38.9:1 (ii) another important characteristic of the presented antenna is its larger bandwidth dimension ratio (BDR) value of 6596 that is accomplished by augmenting the electrical length of the patch. The electrical dimension of the proposed antenna is 0.18λ×0.16λ (λ corresponds to the lower end operating frequency). The designed antenna achieves a frequency range from 1.22 to 47.5 GHz with a fractional bandwidth of 190% and exhibiting S11 < -10 dB in simulation. For validating the simulated outcomes, the antenna model is fabricated and measured. Good conformity is established between measured and simulated results. Measured frequency ranges from 1.25 to 40 GHz with a fractional bandwidth of 188%, BDR of 6523 and S11 < -10 dB. Even though the presented antenna operates properly over the frequency range from 1.22 to 47.5 GHz, the results of the experiment are measured till 40 GHz because of the high-frequency constraint of the existing Vector Network Analyzer (VNA). The designed SWB antenna has the benefit of good gain, concise dimension, and wide bandwidth above the formerly reported antenna structures. Simulated gain varies from 0.5 to 10.3 dBi and measured gain varies from 0.2 to 9.7 dBi. Frequency domain, as well as time-domain characterization, has been realized to guide the relevance of the proposed antenna in SWB wireless applications. Furthermore, an equivalent circuit model of the proposed antenna is developed, and the response of the circuit is obtained. The presented antenna can be employed in L, S, C, X, Ka, K, Ku, and Q band wireless communication systems.

Impulse oscillometry and spirometry exhibit different features of lung function in bronchodilation.

OBJECTIVE: Bronchodilator responses (BDRs) from impulse oscillometry (IOS) are not interchangeable with those from spirometry. We aimed to identify the characteristics of children with small airway hyperresponsiveness and to determine whether BDR from IOS provides an important supplement to BDR from spirometry. METHODS: The records of 592 children with asthma or suspected asthma who underwent spirometric and oscillometric BDRs were retrospectively reviewed. Oscillometric BDR was defined as positive when relative or absolute changes of Rrs5 or Xrs5 were beyond two standard deviations and spirometric BDR as positive when absolute change of forced expiratory volume in one second (FEV1) was ≥12%. Subjects were classified as positive for spirometric BDR only, positive for oscillometric BDR only, positive for both BDRs, or negative for both BDRs. RESULTS: The results indicated that 101 (17.6%) subjects were positive for spirometric BDR only, 49 (8.5%) positive for oscillometric BDR only, 48 (8.3%) positive for both BDRs, and 377 (65.6%) negative for both BDRs. The agreement between spirometric and oscillometric BDRs was poor. Baseline FEV1, Rrs5, and Xrs5 values strongly influenced the BDRs. Subjects positive for oscillometric BDR only were found to be younger than those positive for spirometric BDR only (P < 0.001). Subjects positive for both BDRs were more likely to have asthma, atopic dermatitis, wheezing apart from cold, or decreased baseline lung function relative to those positive in either test (P < 0.001). CONCLUSIONS: There was a low concordance between spirometric and oscillometric BDRs. Use of IOS to detect small airway hyperresponsiveness may add more information about a clinical profile of subjects with asthma.

A genome-wide association study of bronchodilator response in Latinos implicates rare variants.

BACKGROUND: The primary rescue medication to treat acute asthma exacerbation is the short-acting ß2-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). OBJECTIVE: To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. METHODS: We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. RESULTS: We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P < 5 × 10(-8)), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, <5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. CONCLUSION: Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR.

Diagnostic accuracy of the bronchodilator response in children.

BACKGROUND: The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood. OBJECTIVES: We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts. METHODS: Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program. Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs. RESULTS: A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%). Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%). CONCLUSIONS: Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.

A high bandwidth dimension ratio compact super wide band-flower slotted microstrip patch antenna for millimeter wireless applications.

A compact high bandwidth ratio (BDR) super wide band flower slotted micro strip patch antenna (SWB-FSMPA) for super wide band (SWB) applications is presented. The SWB-FSMPA is constructed on a FR-4 substrate having a size of 16 × 22 mm2. The SWB-FSMPA incorporates a 50 Ω tapered micro strip line and a rectangular beveled defected ground structure (RB-DGS). This design enables a simulation bandwidth from 3.78 to 109.86 GHz, allowing for coverage of various wireless applications such as WiMAX (3.3-3.6 GHz), 5G (3.3-3.7 GHz), WLAN (5.15-5.825 GHz), UWB (3.1-10.6 GHz), Ku- (12-18 GHz), K- (18-27 GHz), Ka- (27-40 GHz), V- (40-75 GHz), and W- (75-110 GHz) millimeter wave bands. The SWB-FSMPA antenna exhibits a gain that varies within the range of 3.22-7.23 dBi and a peak efficiency of 93.3 %. The SWB-FSMPA possesses a bandwidth ratio (BR) of 29.1:1, a BDR of 5284 in the frequency domain, a minimal group delay (GD) fluctuation of <0.48 ns, and a linear phase in the time domain, making it well-suited for SWB applications.

Bronchodilator Responsiveness Measured by Spirometry and Impulse Oscillometry in Patients with Asthma After Short Acting Antimuscarinic and/or Beta-2-Agonists Inhalation.

Background: Bronchodilator responsiveness (BDR) in asthma involves both the central and peripheral airways but is primarily relieved with beta-2-agonists and evaluated by spirometry. To date, antimuscarinics can be added as a reliever medication in more severe asthma. We hypothesize that combining both short-acting beta-2 agonist (SABA) and short-acting muscarinic antagonist (SAMA) could also improve the responsiveness in mild-moderate asthma. Therefore, we aimed to compare the direct effects of inhaling SABA alone, SAMA alone or combining both SABA and SAMA on the central and peripheral airways in asthma. Methods: Twenty-three patients with mild-moderate BDR in asthma performed dynamic spirometry and impulse oscillometry before (baseline) and multiple timepoints within an hour after inhalation of SABA (salbutamol), SAMA (ipratropium bromide), or both SABA and SAMA at three different visits. Results: The use of SAMA alone did not show any improvement compared to the use of SABA alone. Inhalation of SABA+SAMA, however, averaged either similar or better BDR than SABA alone in FEV1, MMEF, FVC, R5, R20 and R5-R20. Inhaling SABA+SAMA reached a stable BDR in more patients within 0-10 minutes and also reached the FEV1 (Δ%)>12% faster (3.5 minutes) than inhaling SABA alone (5.1 minutes). Inhaling SABA+SAMA was significantly better than SAMA alone in FEV1 (p = 0.015), MMEF (p = 0.0059) and R20 (p = 0.0049). Using these three variables highlighted a subgroup (30%, including more males) of patients that were more responsive to inhaling SABA+SAMA than SABA alone. Conclusion: Overall, combining SAMA with SABA was faster and more consistent at increasing the lung function than SABA alone or SAMA alone, and the additive effect was best captured by incorporating peripheral-related variables. Therefore, SAMA should be considered as an add-on reliever for mild-moderate patients with BDR in asthma.

Antibacterial and antibiofilm activities of bacteriocin produced by a new strain of Enterococcus faecalis BDR22.

A large number of recalcitrant bacterial pathogens cannot be easily treated by antibiotics due to the existence of biofilm. Hence, an alternative strategy needs to be adopted to remove the biofilm without the development of antibiotic resistance. Bacteriocins, ribosome-mediated proteinaceous toxins, having potential to inhibit the growth of closely or distantly related bacteria. In the present study, after screening a number of sources, a bacteriocin-producing strain, Enterococcus faecalis BDR22, was isolated that showed a significant reduction in the growth of planktonic cells of Gram-positive Staphylococcus aureus, Bacillus subtilis, and Gram-negative Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Klebsiella pneumoniae compared to the conventional antibiotic tetracycline. The considerable reduction of the biofilm-forming sessile cells of the test organisms S. aureus (ATCC 23235) and P. aeruginosa (ATCC 10145), with no significant cell revival even after withdrawal of the treatment, was also observed. The extracellular polymeric substance (EPS) content of the biofilm was also reduced, with around 84% total carbohydrate reduction found for both microorganisms. The antibiofilm activities of the strain against test organisms were clearly visible from scanning electron micrographs and confirmed by the changes in functional groups (C-H, -OH, C = C, C-N etc.) of biofilm matrices by Fourier transform infrared spectroscopy (FTIR) analysis. The molecular docking interactions with docking energies ∆G of - 54.40 kcal/mol and - 66.2373 kcal/mol validate the affinity of the bacteriocin towards the biofilm-forming protein, which confirms the competence of the bacteriocin-producing strain to act as an effective antimicrobial and antibiofilm agent, replacing antibiotics.

Gene Association Study of the Urokinase Plasminogen Activator and Its Receptor Gene in Alzheimer's Disease.

Background: The role of the innate immune system has long been associated with Alzheimer's disease (AD). There is now accumulating evidence that the soluble Urokinase Plasminogen Activator Receptor pathway, and its genes, PLAU and PLAUR may be important in AD, and yet there have been few genetic association studies to explore this. Objective: This study utilizes the DNA bank of the Brains for Dementia Research cohort to investigate the genetic association of common polymorphisms across the PLAU and PLAUR genes with AD. Methods: TaqMan genotyping assays were used with standard procedures followed by association analysis in PLINK. Results: No association was observed between the PLAU gene and AD; however, two SNPs located in the PLAUR gene were indicative of a trend towards association but did not surpass multiple testing significance thresholds. Conclusions: Further genotyping studies and exploration of the consequences of these SNPs on gene expression and alternative splicing are warranted to fully uncover the role this system may have in AD.

Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.

Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10-8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10-9) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

Iron-based and BRD4-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-II-boosted nano-matchbox.

Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

Effects of the salbutamol bronchodilator response on measurements of fractional exhaled nitric oxide in children with asthma: a prospective, observational study.

Background: Salbutamol bronchodilator response (BDR) test and fractional exhaled nitric oxide (FeNO) have been recommended for the diagnosis of asthma in children, but FeNO levels is affected by many factors. Nonetheless, data of the effect on the FeNO values throughout the bronchodilator test and the differences in FeNO values between BDR positive (BDR+) and negative (BDR-) children with asthma are still limited. We aimed to evaluate the effect of the BDR test on FeNO and the differences in FeNO levels between BDR+ and BDR- children with asthma. Methods: This was a prospective, observational study performed over a 5-month period (December 2018 to April 2019) and involved 57 children with asthma. The FeNO levels at pre-spirometry, post-spirometry, and post-salbutamol BDR testing were estimated. Finally, the children were divided into two groups i.e., BDR+ and BDR-, and differences in the FeNO levels were compared between the two groups. Results: The spirometry results were normal in 2 patients (3.5%). There were 53 (93%) patients with obstructive lung disease, including 40 (70.2%), 11 (19.3%), and 2 (3.5%) patients with mild, moderate, and severe obstruction, respectively. The remaining two patients had mixed lesions (3.5%), none of which were restrictive. The baseline median FeNO levels were significantly higher in the BDR+ group than in the BDR- group [33.00 (23.78, 46.73) vs. 23.00 (9.80, 37.80), (P=0.048)]. Following spirometry, there was a statistically significant decrease in median FeNO levels from baseline to post-spirometry (P=0.002). However, there was no significant difference between the median FeNO levels at baseline and following the BDR test (P=0.976). The impact of spirometry on FeNO was not statistically different in BDR+ versus BDR- children (Z=-0.186, P=0.853); however, the impact of bronchodilators on FeNO exhibited a statistically significant difference between the two groups (Z=3.160, P=0.002). Conclusions: This study revealed dynamic changes in the FeNO levels during the BDR test. The use of a bronchodilator results in a statistically significant difference in FeNO levels between BDR+ and BDR- children with asthma. Moreover, spirometry leads to a marked decrease in the FeNO levels. Our results will allow clinicians to better interpret FeNO, BDR and pulmonary function outcomes and better develop clinical protocols.

Genome-wide association findings from the brains for dementia research cohort.

The Brains for Dementia Research (BDR) cohort (~3200) is a longitudinal clinicopathological programme, complimented with genetic analysis for the purposes of aetiological investigation into dementia. Here the data from genetic association analyses are presented from the initial collection of DNA from the BDR cohort. The aim of this study was to investigate the preliminary association signals for pathologically confirmed Alzheimer's disease samples compared to controls with no other pathology (n = 520). Genome-wide genotyping was carried out using the NeuroChip platform. Analysis utilised the standard PLINK software for association studies. Genome-wide Bonferroni significant association were observed on chr19 around the APOE/TOMM40 locus across 2 distinct linkage disequilibrium blocks. Eleven of the top 35 association signals have been identified in previous studies, in addition to an intriguing SNP association within the FPR1 gene locus. This study suggests the BDR is genetically comparable to other Alzheimer's disease cohorts and offers an independent resource to verify findings, and additional genetic data for meta-analyses.

Plasmalogens Mediate the Effect of Age on Bronchodilator Response in Individuals With Asthma.

Background: Asthma is known to display different phenotypes across the life-course, suggesting that age related changes are particularly relevant to understanding asthma pathogenesis and remission. We have previously demonstrated that a lung function phenotype associated with asthma, bronchodilator response, is reduced with age, at rate of 0.24 percent per year. Methods: In this study, we interrogated the serum metabolome, to determine whether circulating metabolites mediate age-related changes in bronchodilator response (BDR) for individuals with asthma. We used data on 295 participants from the follow-up phase of the CAMP clinical trial (age 12.2-25.9 years; mean BDR of 8%, standard deviation 7%). Using a counterfactual framework, we analyzed over 500 pareto-scaled metabolites using mediation analysis to identify indirect effects of age through potential metabolite mediators. Results: There was a significant indirect effect of age on BDR through 4 plasmalogens (C36:1 PC and related metabolites) (Indirect Effect Beta = -0.001, p = 0.006). Conclusions: Our findings suggest that plasmalogens may contribute to age-related asthma phenotypes, and may also serve as potential pharmacologic targets for enhancement of lung function in individuals with asthma. Trial Registration: This work uses data from the previous clinical trial of asthma, the Childhood Asthma Management Program (CAMP), registered at ClinicalTrials.gov, # NCT00000575.

Comparison of different surgical interventions for hepatocellular carcinoma with bile duct tumor thrombus: a systematic review and meta-analysis.

BACKGROUND: The optimal surgical modality for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial, especially regarding deciding whether to perform concurrent bile duct resection (BDR). METHODS: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were systematically searched from inception to February 2020, in order to compare overall survival (OS) and recurrence-free survival (RFS) rates of HCC patients with BDTT who had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Relevant outcomes were extracted by two investigators. RESULTS: A total of 12 studies involving 355 patients was included. The 1-, 3- and 5-year OS rates were similar in the BDR and NBDR groups (OR =0.58, 95% CI: 0.31-1.09, P=0.09; OR =0.74, 95% CI: 0.43-1.28, P=0.28; OR =0.63, 95% CI: 0.36-1.11, P=0.11, respectively). However, the BDR group had better 1-, 3- and 5-year RFS rates than the NBDR group (OR =0.38, 95% CI: 0.22-0.65, P<0.01; OR =0.40, 95% CI: 0.22-0.72, P<0.01; OR =0.37, 95% CI: 0.19-0.71, P<0.01, respectively). CONCLUSIONS: Concomitant bile duct resection results in decreased postoperative recurrence in HCC patients with BDTT. However, the OS rates were similar whether or not patients underwent bile duct resection.

Usefulness of impulse oscillometry for the assessment of bronchodilator response in elderly patients with chronic obstructive airway disease.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive and convenient technique to measure both airway resistance and reactance. This study aimed to evaluate whether IOS can be used to measure bronchodilator response (BDR) in elderly patients with asthma and chronic obstructive pulmonary disease (COPD) and also describe the difference between asthma and COPD. METHODS: Seventy patients (30 and 40 with asthma and COPD, respectively) over 65 years of age were enrolled. IOS and spirometry measurements were obtained before and after bronchodilator administration. Correlation analysis was used to compare the percentage changes in spirometry and IOS parameters after bronchodilator administration between the asthma and COPD groups. RESULTS: The changes in IOS parameters after bronchodilator administration were strongly correlated with changes in forced expiratory volume at 1 second (FEV1) and forced expiratory flow at 25-75% (FEF25-75). However, the percentage changes in IOS parameters failed to discriminate between the asthma and COPD groups. Receiver operating characteristic curve (ROC) analysis of resistance at 5 and 20 Hz (R5-20) at the best cutoff (-15.4% change) showed both high sensitivity and specificity for BDR. CONCLUSIONS: IOS serves as a reliable and useful technique for identifying BDR in elderly patients with chronic obstructive airway disease. There was a difference in IOS parameters between the asthma and COPD groups; however, it was difficult to distinguish between both diseases. Further larger studies are required to investigate the real implications of using IOS in the clinical practice.

Regional lung ventilation pattern in preschool children with bronchopulmonary dysplasia is modified by bronchodilator response.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a significant long-term complication of prematurity. A standardized method of pulmonary function testing is still not available in preschool children with BPD. We investigated the feasibility of Electrical Impedance Segmentography (EIS) monitoring in this group and the impact of bronchodilator response (BDR) to salbutamol on the pattern of lung ventilation. METHODS: We conducted a follow-up study of 4-year-old premature children who had been treated in the tertiary NICU. The cohort was divided into two groups based on the presence of BPD. EIS monitoring was performed before and 15 min after the administration of 400 µg of salbutamol (pMDI with spacer) in all subjects during spontaneous tidal breathing in upright position. Data were expressed as median segmental impedance amplitude differences and segmental ventilation inhomogeneity index (II) changes. RESULTS: We included 51 children in our analysis: 33 with BPD (median birth weight-840 g; median gestational age-27 weeks) and 18 without BPD (1,290 g; 30 weeks, respectively). There was a significant increase in median segmental impedance amplitude after salbutamol in gravity non-dependent segments in children with BPD: upper left (UL): 462 versus 534 AU; (P = 0.003); upper right (UR): 481 versus 595 AU (P < 0.001) and II in these segments: UL: 0.046 versus 0.078 (P = 0.003) UR: 0.049 versus 0.064 (P = 0.006). There were no changes in the lower segments. There were no changes in ventilation pattern in children without BPD. CONCLUSION: BDR to salbutamol increases breath amplitude in gravity non-dependent segments of the lungs during spontaneous tidal breathing in preschool children with BPD. Pediatr Pulmonol. 2017;52:353-359. © 2016 Wiley Periodicals, Inc.