CubeX: A Compact X-ray Telescope Enables Both X-ray Fluorescence Imaging Spectroscopy and Pulsar Timing Based Navigation

This paper describes the miniaturized X-ray telescope payload, CubeX, in the context of a lunar mission. The first part describes the payload in detail, the second part summarizes a small satellite mission concept that utilizes its compact form factor and performance. This instrument can be used for both X-ray fluorescence (XRF) imaging spectroscopy and X-ray pulsar timing-based navigation (XNAV). It combines high angular resolution (\u3c 1 \u3earcminutes) Miniature Wolter-I X-ray optics (MiXO) with a common focal plane consisting of high spectral resolution (keV) CMOS X-ray sensors and a high timing resolution (\u3c 1 μsec) SDD X-ray sensor. This novel combination of the instruments enables both XRF measurements and XNAV operations without moving parts, in a small form factor (~1×1×6U

An Experimental Paradigm for the Prediction of Post-Operative Pain (PPOP)

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in São Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery

Use of a Cross-Sectional Survey in the Adult Population to Characterize Persons at High-Risk for Chronic Obstructive Pulmonary Disease

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Methods: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥ 10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease burden was defined by respiratory symptoms and health impairments. Data were analyzed using multiple logistic regression models with age as a covariate. Results: Among 35,722 adults ≥ 18 years, the overall prevalence of COPD and high-risk for COPD were 6.6% and 5.1%. Differences among COPD risk groups were evident based on gender, race, age, geography, tobacco use, health impairments, and respiratory symptoms. Risk for disease was seen early where 3.75% of 25–34 years-old met high-risk criteria. Longer tobacco duration was associated with an increased prevalence of COPD, particularly \u3e 20 years. Seventy-nine percent of persons ≥ 45 years-old with frequent shortness of breath (SOB) reported having or being at risk of COPD, reflecting disease burden. Conclusion: These data, representing nearly 18% of US adults, indicates those at high risk for COPD share many, but not all of the characteristics of persons diagnosed with the disease and demonstrates the value of the BRFSS as a tool to define lung health at a population level

Smoking Duration, Respiratory Symptoms, and COPD in Adults Aged ≥45 Years with a Smoking History

BACKGROUND: The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012. METHODS: Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design. RESULTS:The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years). Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD. Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers. Smoking duration had a linear relationship with COPD (P\u3c0.001) and all three respiratory symptoms (P\u3c0.001) after adjusting for smoking status and other covariates. While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1–9 years, 20–29 years, and ≥30 years duration periods. CONCLUSION:These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior

Tollip deficiency exaggerates airway type 2 inflammation in mice exposed to allergen and influenza A virus: role of the ATP/IL-33 signaling axis

Toll-interacting protein (Tollip) is a negative regulator of the pro-inflammatory response to viruses, including influenza A virus (IAV). Genetic variation of Tollip has been associated with reduced airway epithelial Tollip expression and poor lung function in patients with asthma. Whether Tollip deficiency exaggerates type 2 inflammation (e.g., eosinophils) and viral infection in asthma remains unclear. We sought to address this critical, but unanswered question by using a Tollip deficient mouse asthma model with IAV infection. Further, we determined the underlying mechanisms by focusing on the role of the ATP/IL-33 signaling axis. Wild-type and Tollip KO mice were intranasally exposed to house dust mite (HDM) and IAV with or without inhibitors for IL-33 (i.e., soluble ST2, an IL-33 decoy receptor) and ATP signaling (i.e., an antagonist of the ATP receptor P2Y13). Tollip deficiency amplified airway type 2 inflammation (eosinophils, IL-5, IL-13 and mucins), and the release of ATP and IL-33. Blocking ATP receptor P2Y13 decreased IL-33 release during IAV infection in HDM-challenged Tollip KO mice. Furthermore, soluble ST2 attenuated airway eosinophilic inflammation in Tollip KO mice treated with HDM and IAV. HDM challenges decreased lung viral load in wild-type mice, but Tollip deficiency reduced the protective effects of HDM challenges on viral load. Our data suggests that during IAV infection, Tollip deficiency amplified type 2 inflammation and delayed viral clearance, in part by promoting ATP signaling and subsequent IL-33 release. Our findings may provide several therapeutic targets, including ATP and IL-33 signaling inhibition for attenuating excessive airway type 2 inflammation in human subjects with Tollip deficiency and IAV infection

MARE-1 in Milan: Status and Perspectives

The international project MARE (Microcalorimeter Array for a Rhenium Experiment) aims at the direct and calorimetric measurement of the electron neutrino mass with sub-eV sensitivity. Although the baseline of the MARE project consists in a large array of rhenium based thermal detectors, a different option for the isotope is also being considered. The different option is 163Ho. The potential of using 187Re for a calorimetric neutrino mass experiment has been already demonstrated. On the contrary, no calorimetric spectrum of 163Ho has been so far measured with the precision required to set a useful limit on the neutrino mass. The first phase of the project (MARE-1) is a collection of activities with the aim of sorting out both the best isotope and the most suited detector technology to be used for the final experiment. One of the MARE-1 activities is carried out in Milan by the group of Milano–Bicocca in collaboration with NASA/GSFC and Wisconsin groups. The Milan MARE-1 arrays are based on semiconductor thermistors, provided by the NASA/GSFC group, with dielectric silver perrhenate absorbers, AgReO4. The experiment, which is presently being assembled, is designed to host up to 8 arrays. With 288 detectors, a sensitivity of 3 eV at 90% CL on the neutrino mass can be reached within 3 years. This contribution gives an outlook for the MARE activities for the active isotope selection. In this contribution the status and the perspectives of the MARE-1 in Milan are also reported

Glucocorticoid receptor expression on circulating leukocytes differs between healthy male and female adults

IntroductionThe glucocorticoid receptor (GR) is a key receptor involved in inflammatory responses and is influenced by sex steroids. This study measured GR expression on circulating leukocyte subtypes in males and females.MethodsA total of 23 healthy adults (12 female) participated in this study. GR expression was measured in leukocyte subtypes using flow cytometry. Peripheral blood mononuclear cell (PBMC) gene expression of GR (NR3C1), GR β, TGF-β1 and 2, and glucocorticoid-induced leucine zipper (GILZ) were determined by real-time polymerase chain reaction.ResultsLeukocyte GR was lower in females, particularly in granulocytes, natural killer cells, and peripheral blood mononuclear cells (p≤0.01). GR protein expression was different across leukocyte subtypes, with higher expression in eosinophils compared with granulocytes, T lymphocytes, and natural killer cells (p<0.05). There was higher gene expression of GR β in males (p=0.03).ConclusionsThis is the first study to identify sexual dimorphism in GR expression in healthy adults using flow cytometry. These results may begin to explain the sexual dimorphism seen in many diseases and sex differences in glucocorticoid responsiveness

The role of small airway dysfunction in asthma control and exacerbations:a longitudinal, observational analysis using data from the ATLANTIS study

Background Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.Methods In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.Findings 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0.20-0.25, p<0.0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.Interpretation Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved

B cell–adaptive immune profile in emphysema-predominant chronic obstructive pulmonary disease

Cigarette smoke, the major risk factor for COPD in developed countries, causes pulmonary inflammation that persists long after smoking cessation, suggesting self-perpetuating adaptive immune responses similar to those that occur in autoimmune diseases. Increases in the number and size of B cell–rich lymphoid follicles (LFs) have been shown in patients in severe stages of COPD (4), and increased B-cell products (autoantibodies) have been observed in the blood and lungs of patients with COPD (5, 6). Oligoclonal rearrangement of the immunoglobulin genes has been observed in B cells isolated from COPD LFs, suggesting that a specific antigenic stimulation drives B-cell proliferation. Consistently, we have shown that in the COPD lung, there is an overexpression of BAFF (B-cell activation factor of the TNF family), which is a key regulator of B-cell homeostasis in several autoimmune diseases (7) and is involved in the growth of LFs in COPD. However, a network analysis of lung transcriptomics showed that a prominent B-cell molecular signature characterized emphysema preferentially but was absent in AD independently of the degree of airflow limitation (8). In the current study, we investigated the correlation between B-cell responses in lung tissue from patients with COPD and healthy smokers, and the extent of emphysema versus airflow limitation