Adv Nanobiomed Res. 2021 May 6;1(6):2000111. doi: 10.1002/anbr.202000111. eCollection 2021 Jun.

ABSTRACT

Air-liquid interface (ALI) culture models currently represent a valid instrument to recreate the typical aspects of the respiratory tract in vitro in both healthy and diseased state. They can help reducing the number of animal experiments, therefore, supporting the 3R principle. This review discusses ALI cultures and co-cultures derived from immortalized as well as primary cells, which are used to study the most common disorders of the respiratory tract, in terms of both pathophysiology and drug screening. The article displays ALI models used to simulate inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, lung cancer, and viral infections. It also includes a focus on ALI cultures described in literature studying respiratory viruses such as SARS-CoV-2 causing the global Covid-19 pandemic at the time of writing this review. Additionally, commercially available models of ALI cultures are presented. Ultimately, the aim of this review is to provide a detailed overview of ALI models currently available and to critically discuss them in the context of the most prevalent diseases of the respiratory tract.

PMID:34345878 | PMC:PMC7611446 | DOI:10.1002/anbr.202000111

Cureus. 2021 Jul 1;13(7):e16087. doi: 10.7759/cureus.16087. eCollection 2021 Jul.

ABSTRACT

Acute respiratory failure in cystic fibrosis carries a high risk of mortality. The optimal mode of mechanical ventilation (MV) in this population is not well established. In this case series, we identified patients with cystic fibrosis who were ventilated with high-frequency percussive ventilation (HFPV) at our institution and describe their characteristics and outcomes. The use of high-frequency percussive ventilation has been sparsely described in the literature. This case series could serve as hypothesis-generating for future research.

PMID:34345563 | PMC:PMC8325394 | DOI:10.7759/cureus.16087

Clin Med Insights Endocrinol Diabetes. 2021 Jul 13;14:11795514211031204. doi: 10.1177/11795514211031204. eCollection 2021.

ABSTRACT

Cystic fibrosis-related diabetes mellitus (CFRD) is the most common non-pulmonary co-morbidity in cystic fibrosis (CF). CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which leads to aberrant luminal fluid secretions in organs such as the lungs and pancreas. How dysfunctional CFTR leads to CFRD is still under debate. Both intrinsic effects of dysfunctional CFTR in hormone secreting cells of the islets and effects of exocrine damage have been proposed. In the current review, we discuss these non-mutually exclusive hypotheses with a special focus on how dysfunctional CFTR in endocrine cells may contribute to an altered glucose homeostasis. We outline the proposed role of CFTR in the molecular pathways of β-cell insulin secretion and α-cell glucagon secretion, and touch upon the importance of the exocrine pancreas and intra-pancreatic crosstalk for proper islet function.

PMID:34345195 | PMC:PMC8280842 | DOI:10.1177/11795514211031204

Int J Chron Obstruct Pulmon Dis. 2021 Jul 21;16:2133-2148. doi: 10.2147/COPD.S310428. eCollection 2021.

ABSTRACT

INTRODUCTION: Understanding clinical evolution of chronic obstructive pulmonary disease (COPD) is crucial for improving disease management.

MATERIALS AND METHODS: STORICO (NCT03105999), an Italian, multicenter, non-interventional, observational study conducted in 40 pulmonology centers, aimed to describe the 1-year clinical evolution and health status of clinicallbased phenotypes. Baseline and follow-up data of COPD subjects with a chronic bronchitis (CB) or emphysema (EM) phenotype were collected. The frequency of COPD symptoms during the 24 hours (gathered via the night-time, morning and day-time symptoms of COPD questionnaire) and the anxiety and depression levels (via the HADS Scale) were recorded at each visit.

RESULTS: A total of 261 CB and 159 EM patients were analyzed. CB patients with ≥1 night-time symptom seemed to be more frequent (51.7%, 41.8% and 41.4% at baseline, 6-month and 12-month follow-up, respectively) than EM (37.7%, 32.1% and 30.2% at study visits) even if no statistical differences were observed at time points between phenotypes (chi-square test p-values presence/absence of night-time symptoms in CB vs EM at study visits >0.0007). In the first 6 months, the frequency of patients with ≥1 night-time symptom decreased of 9.9% in CB and of 5.6% in EM. A clinically relevant decline of DLCO % predicted over 1 year in EM was observed, the mean (SD) being 61.5 (20.8) % at baseline and 59.1 (17.4) % at 12-month follow-up. EM had higher levels of anxiety and depression than CB (median (25th-75th percentile) HADS total score in CB: 7.0 (4.0-13.0) and 7.0 (3.0-12.0), in EM: 9.0 (3.0-14.0) and 9.5 (3.0-14.0) both at baseline and at 6-month follow-up, respectively), considering 1.17 as minimally clinical important difference (MCID) for the total score.

CONCLUSION: EM patients, evaluated in a real-world setting, seem to suffer from a worse clinical condition and health status compared to CB patients, appearing to have "more treatable" traits.

PMID:34345170 | PMC:PMC8325060 | DOI:10.2147/COPD.S310428

Sci Rep. 2021 Aug 3;11(1):15757. doi: 10.1038/s41598-021-95366-z.

ABSTRACT

This study investigated the impact of bronchiectasis on patients admitted to the intensive care unit (ICU) at a hospital in Korea. Patients with bronchiectasis were diagnosed using results of chest computed tomography performed before ICU admission. The severity of bronchiectasis was based on the number of affected lobes, and patients with ≥ 3 bronchiectatic lobes were classified into the severe bronchiectasis group. Overall, 823 patients were enrolled. The mean age was 66.0 ± 13.9 years, and 63.4% were men. Bronchiectasis and severe bronchiectasis were present in 148 (18.0%) and 108 (13.1%) patients, respectively. The increase in the number of bronchiectatic lobes was related to the rise in ICU mortality (P for trend = 0.012) and in-hospital mortality (P for trend = 0.004). Patients with severe bronchiectasis had higher odds for 28-day mortality [odds ratio (OR) 1.122, 95% confidence interval (CI) 1.024-1.230], ICU mortality (OR 1.119, 95% CI 1.023-1.223), and in-hospital mortality (OR 1.208, 95% CI 1.092-1.337). The severe bronchiectasis group showed lower overall survival (log-rank P < 0.001), and the adjusted hazard ratio was 1.535 (95% CI 1.178-2.001). Severe bronchiectasis had a negative impact on all-cause mortality during ICU and hospital stays, resulting in a lower survival rate.

PMID:34345008 | DOI:10.1038/s41598-021-95366-z

Am J Respir Crit Care Med. 2021 Aug 3. doi: 10.1164/rccm.202106-1383ED. Online ahead of print.

NO ABSTRACT

PMID:34343466 | DOI:10.1164/rccm.202106-1383ED

Ann Acad Med Singap. 2021 Jul;50(7):556-565.

ABSTRACT

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality.

METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented.

RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, P<0.001) and a significantly larger proportion with post-tuberculous bronchiectasis (37.0% vs 15.8%, P=0.002). Fifty-five percent of our cohort had a history of haemoptysis. Lower body mass index, presence of chronic obstructive pulmonary disease, ever-smoker status, modified Reiff score, radiological severity and history of exacerbations were risk factors for mortality. Survival was significantly shorter in patients with severe bronchiectasis (BSI>9) compared to those with mild or moderate disease (BSI<9). The hazard ratio for severe disease (BSI>9) compared to mild disease (BSI 0-4) was 14.8 (confidence interval 1.929-114.235, P=0.01).

CONCLUSION: The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

PMID:34342336

Nat Chem Biol. 2021 Aug 2. doi: 10.1038/s41589-021-00844-0. Online ahead of print.

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is essential to maintain fluid homeostasis in key organs. Functional impairment of CFTR due to mutations in the cftr gene leads to cystic fibrosis. Here, we show that the first nucleotide-binding domain (NBD1) of CFTR can spontaneously adopt an alternate conformation that departs from the canonical NBD fold previously observed. Crystallography reveals that this conformation involves a topological reorganization of NBD1. Single-molecule fluorescence resonance energy transfer microscopy shows that the equilibrium between the conformations is regulated by adenosine triphosphate binding. However, under destabilizing conditions, such as the disease-causing mutation F508del, this conformational flexibility enables unfolding of the β-subdomain. Our data indicate that, in wild-type CFTR, this conformational transition of NBD1 regulates channel function, but, in the presence of the F508del mutation, it allows domain misfolding and subsequent protein degradation. Our work provides a framework to design conformation-specific therapeutics to prevent noxious transitions.

PMID:34341587 | DOI:10.1038/s41589-021-00844-0

J Tissue Eng Regen Med. 2021 Aug 2. doi: 10.1002/term.3234. Online ahead of print.

ABSTRACT

The mechanical environment of living cells is as critical as chemical signaling. Mechanical stimuli play a pivotal role in organogenesis and tissue homeostasis. Unbalances in mechanotransduction pathways often lead to diseases, such as cancer, cystic fibrosis, and neurodevelopmental disorders. Despite its inherent relevance, there is a lack of proper mechanoresponsive in vitro study systems. In this context, there is an urge to engineer innovative, robust, dynamic, and reliable organotypic technologies to better connect cellular processes to organ level-function and multi-tissue cross-talk. Mechanically active organoid-on-chip has the potential to surpass this challenge. These systems converge microfabrication, microfluidics, biophysics, and tissue engineering fields to emulate key features of living organisms, hence, reducing costs, time, and animal testing. In this review, we intended to present cutting-edge organ-on-chip platforms that integrate biomechanical stimuli as well as novel multicellular culture, such as organoids. We focused on its application in two main fields: Precision medicine and drug development. Moreover, we also discussed the state-of-the-art for the development of an engineered model to assess patient-derived tumor organoid metastatic potential. Finally, we highlighted the current drawbacks and emerging opportunities to match the industry needs. We envision the use of mechanoresponsive organotypic-on-chip microdevices as an indispensable tool for precision medicine, drug development, disease modeling, tissue engineering, and developmental biology. This article is protected by copyright. All rights reserved.

PMID:34339588 | DOI:10.1002/term.3234

J Bacteriol. 2021 Aug 2:JB0031121. doi: 10.1128/JB.00311-21. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF) is a heritable, multi-organ disease that impacts all tissues that normally express CFTR protein. While importance of the airway microbiota has long been recognized, the intestinal microbiota has only recently been recognized as an important player in both intestinal and lung health outcomes for persons with CF (pwCF). Here, we summarize current literature related to the gut-lung axis in CF, with a particular focus on three key ideas: Mechanisms through which microbes influence the gut-lung axis, drivers of microbiota alterations, and the potential for intestinal microbiota remediation.

PMID:34339302 | DOI:10.1128/JB.00311-21

J Bacteriol. 2021 Aug 2:JB0017521. doi: 10.1128/JB.00175-21. Online ahead of print.

ABSTRACT

Streptococcus intermedius, an oral commensal bacterium, is found at various sites including subgingival dental plaque, purulent infections, and in cystic fibrosis lungs. Oral streptococci utilize proteins on their surface to adhere to tissues and/or surfaces localizing the bacteria, which subsequently leads to the development of biofilms, colonization and infection. Among the 19 genomically annotated cell-wall attached surface proteins on S. intermedius, Pas is an adhesin that belongs to the Antigen I/II (AgI/II) family. Here we have structurally and functionally characterized Pas, particularly focusing on its microbial-host as well as microbial-microbial interactions. The crystal structures of VPas and C123Pas show high similarity with AgI/II of S. mutans. VPas hosts a conserved metal binding site, and likewise the C123Pas structure retains its conserved metal binding sites and isopeptide bonds within its three DEv-IgG domains. Pas interacts with nanomolar affinity to lung alveolar glycoprotein 340 (Gp340), its scavenger receptor cysteine rich domains (SRCRs) and with fibrinogen. Both Candida albicans and Pseudomonas aeruginosa, the opportunistic pathogens that cohabitate with S. intermedius in the lungs of CFTR patients were studied in dual-species biofilm studies. The Pas deficient mutant (Δpas) displayed significant reduction in dual biofilm formation with C. albicans. In similar studies with P. aeruginosa, Pas did not mediate the biofilm formation with either the acute isolate (PAO1), or the chronic isolate (FRD1). However, the Sortase A deficient mutant (ΔsrtA) displayed reduced biofilm formation with both C. albicans and P. aeruginosa FRD1. Taken together, our findings highlight the role of Pas in both microbial-host and interkingdom interactions and expose its potential role in disease outcomes. Importance Streptococcus intermedius, an oral commensal bacterium, has been clinically observed in subgingival dental plaque, purulent infections, and in cystic fibrosis lungs. In this study, we have (a) determined the crystal structure of the V- and C-regions of Pas; (b) shown that its surface protein Pas adheres to fibrinogen, which could potentially ferry the microbe through the blood stream from the oral cavity; (c) characterized Pas's high affinity adherence to lung alveolar protein Gp340 that could fixate the microbe on lung epithelial cells; and (d) most importantly shown that these surface proteins on the oral commensal S. intermedius enhances biofilms of known pathogens Candida albicans and Pseudomonas aeruginosa.

PMID:34339301 | DOI:10.1128/JB.00175-21

J Bacteriol. 2021 Aug 2:JB0014521. doi: 10.1128/JB.00145-21. Online ahead of print.

ABSTRACT

FleQ plays a crucial role in motility and biofilm formation by regulating flagellar and exopolysaccharide biosynthesis in Pseudomonas aeruginosa. It has been reported that the expression of FleQ is transcriptionally downregulated by the virulence factor regulator Vfr. Herein we demonstrated that a LysR-type transcriptional regulator, OsaR, is also capable of binding to the promoter region of fleQ and repressing its transcription. Through gel shift and DNase I footprinting assays, the OsaR binding site was identified and characterized as a dual LysR-type transcriptional regulator box (AT-N11-AT-N7-A-N11-T). Mutation of the A-T palindromic base pairs in fleQ promoter not only reduced the binding affinity of OsaR in vitro, but also de-repressed fleQ transcription in vivo. The OsaR binding site was found to cover the Vfr binding site; knockout of osaR or vfr separately exhibited no effect on the transcriptional level of fleQ; however, fleQ expression was repressed by overexpression of osaR or vfr. Furthermore, simultaneously deleting both osaR and vfr resulted in an upregulation of fleQ, but it could be complemented by the expression of either of the two repressors. In summary, our work revealed that OsaR and Vfr function as two transcriptional repressors of fleQ that bind to the same region of fleQ but work separately. IMPORTANCE Pseudomonas aeruginosa is a widespread human pathogen, which accounts for serious infections in the hospital, especially for lung infection in cystic fibrosis and chronic obstructive pulmonary disease patients. P. aeruginosa infection is closely associated with its motility and biofilm formation, which are both under the regulation of the important transcription factor FleQ. However, the upstream regulatory mechanisms of fleQ have not been fully elucidated. Therefore, our research identifying a novel regulator of fleQ as well as new regulatory mechanisms controlling its expression will be significant for better understanding the intricate gene regulatory mechanisms related to P. aeruginosa virulence and infection.

PMID:34339300 | DOI:10.1128/JB.00145-21

Cochrane Database Syst Rev. 2021 Aug 2;8:CD013488. doi: 10.1002/14651858.CD013488.pub2.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF suffer with pancreatic exocrine insufficiency, which if left untreated, leads to a poor nutritional status. Pancreatic enzyme replacement therapy (PERT) has been shown to be effective in improving nutritional status and subsequently associated with improved lung function. However, the timings of PERT administration in relation to a meal are subjective and not standardised, meaning that variations in the timing of PERT dosing persist.

OBJECTIVES: The primary objective of the review is to compare the efficacy (fat absorption) and effectiveness (nutritional status, lung function and quality of life) of different PERT dosing strategies in terms of timing of administration for treating dietary malabsorption in all individuals with CF.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 24 June 2021. We also searched ongoing trials registers on 09 July 2021.

SELECTION CRITERIA: Randomised controlled trials (RCTs), including cross-over RCTs with a minimum washout period of two weeks, and quasi-RCTs of PERT dosing regimens in people (of any age) with CF.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed and screened the studies identified from the searches. We planned to use GRADE to assess the certainty of evidence for our pre-specified critical outcomes, but we did not identify any eligible studies.

MAIN RESULTS: No studies met the eligibility criteria and therefore we did not include any in this review. The excluded studies were either cross-over in design (but lacking a sufficient washout period between treatments) or did not assess the timing of PERT. One study which was terminated early is awaiting assessment pending further information.

AUTHORS' CONCLUSIONS: We were unable to determine whether one dosing schedule for PERT is better than another since we identified no eligible RCTs. While the introduction of PERT to people with CF can improve their nutritional status, there are a limited number of studies which address this review question, and none met our eligibility criteria. Since malnutrition and adverse gastrointestinal symptoms remain a common feature in CF, the assessment of the relative performance of dosing schedules may provide evidence to improve outcomes in people with CF who are pancreatic insufficient. Further research is needed to fully evaluate the role of dosing schedules for PERT in fat absorption. Research should also establish reliable outcome measures and minimal clinically important differences. While RCTs with a cross-over design may have advantages over a parallel group design, an adequate washout period between intervention periods is essential.

PMID:34339047 | DOI:10.1002/14651858.CD013488.pub2

Percept Mot Skills. 2021 Aug 1:315125211036415. doi: 10.1177/00315125211036415. Online ahead of print.

ABSTRACT

Little is known about motor competence and the longitudinal development of motor performance among youth with cystic fibrosis (CF). In this study, we assessed aspects of motor performance in different age groups of young patients with CF and compared them with a healthy reference group of same aged children. We also examined the development of motor performance among different age groups of these children with CF, using The Deutscher Motorik Test (DMT) to assess attributes of health-related and motor performance-related fitness. We used an incremental ergometer cycle test to determine maximal exercise capacity (expressed as peak workload). We evaluated and recorded habitual physical activity (PA) as measured by the number of steps per day and the time spent in different PA intensities (expressed in metabolic equivalents). In total, 31 children and adolescents with CF agreed to participate (13 girls,18 boys) aged 6-17 years (M = 11.3, SD =3.3 years); they had a mean one second forced expiratory volume (expressed as a percentage of predicted value [% pred]) of 87.2% (SD = 22.3%). We found their values of health-related and motor performance-related fitness to be significantly lower (p < 0.05) than those of their healthy peer participants. In contrast to the reference group, participants with CF up to 14 years of age showed a linear improvement in these values and in their PA, followed by a plateau or even a nonsignificant decrease after age 14. These findings have important implications for the development and prescription of exercise programs for children with CF. Besides aerobic and strength exercises, we recommend that neuromuscular training be integrated into exercise programs to improve the coordinative abilities of youth with CF. More attention should be paid to vulnerable older adolescents to ensure their long-term motivation to maintain exercise participation.

PMID:34338055 | DOI:10.1177/00315125211036415

Br J Hosp Med (Lond). 2021 Jul 2;82(7):1-9. doi: 10.12968/hmed.2020.0739. Epub 2021 Jul 13.

ABSTRACT

Bronchiectasis is a common respiratory condition, characterised by abnormal bronchial dilatation, that often leads to recurrent airway infection and inflammation. It is an increasingly recognised respiratory condition, both as a primary lung disease but also co-existing with other respiratory diseases, such as chronic obstructive pulmonary disease and asthma. Diagnosis can have important treatment implications. There are shared systematic approaches to treatment, such as sputum clearance techniques, prompt treatment of exacerbations and, in certain circumstances, regular antibiotic therapy. It is vital to target antibiotic therapy appropriately, and knowledge of the patient's airway microbiology can assist with this. Certain infective and colonising organisms, such as Pseudomonas aeruginosa, cause worse patient outcomes and so need prompt treatment with appropriate antibiotics. In addition to this general management approach, there are many different underlying causes of bronchiectasis that should be identified wherever possible, to support more targeted therapy and prevent disease progression. This article provides a guide to the key principles of diagnosing and managing bronchiectasis, and outlines situations where more specialist respiratory support is required.

PMID:34338026 | DOI:10.12968/hmed.2020.0739

Magn Reson Med. 2021 Aug 2. doi: 10.1002/mrm.28947. Online ahead of print.

ABSTRACT

PURPOSE: Lung impairment from functional MRI is frequently assessed as defect percentage. The defect distribution, however, is currently not quantified. The purpose of this work was to develop a novel measure that quantifies how clustered or scattered defects in functional lung MRI appear, and to evaluate it in pediatric cystic fibrosis.

THEORY: The defect distribution index (DDI) calculates a score for each lung voxel categorized as defected. The index increases according to how densely and how far an expanding circle around a defect voxel contains more than 50% defect voxels.

METHODS: Fractional ventilation and perfusion maps of 53 children with cystic fibrosis were previously acquired with matrix pencil decomposition MRI. In this work, the DDI is compared to a visual score of 3 raters who evaluated how clustered the lung defects appear. Further, spearman correlations between DDI and lung function parameters were determined.

RESULTS: The DDI strongly correlates with the visual scoring (r = 0.90 for ventilation; r = 0.88 for perfusion; P < .0001). Although correlations between DDI and defect percentage are moderate to strong (r = 0.61 for ventilation; r = 0.75 for perfusion; P < .0001), the DDI distinguishes between patients with comparable defect percentage.

CONCLUSION: The DDI is a novel measure for functional lung MRI. It provides complementary information to the defect percentage because the DDI assesses defect distribution rather than defect size. The DDI is applicable to matrix pencil MRI data of cystic fibrosis patients and shows very good agreement with human perception of defect distributions.

PMID:34337778 | DOI:10.1002/mrm.28947

Oxid Med Cell Longev. 2021 Jul 13;2021:9931742. doi: 10.1155/2021/9931742. eCollection 2021.

ABSTRACT

Neutrophil extracellular traps (NETs) are complexes of decondensed DNA fibers and antimicrobial peptides that are released by neutrophils and play important roles in many noninfectious diseases, such as cystic fibrosis, systemic lupus erythematosus, diabetes, and cancer. Recently, the formation of NETs has been detected in many central nervous system diseases and is thought to play different roles in the occurrence and development of these diseases. Researchers have detected NETs in acute ischemic stroke thrombi, and these NETs are thought to promote coagulation and thrombosis. NETs in ischemic brain parenchyma were identified as the cause of secondary nerve damage. High levels of NETs were also detected in grade IV glioma tissues, where NETs were involved in the proliferation and invasion of glioma cells by activating a signaling pathway. Extracellular web-like structures have also recently been observed in mice with traumatic brain injury (TBI), and it was hypothesized that NETs contribute to the development of edema after TBI. This article reviews the effect of NETs on multiple diseases that affect the CNS and explores their clinical application prospects.

PMID:34336122 | PMC:PMC8294981 | DOI:10.1155/2021/9931742

Front Microbiol. 2021 Jul 14;12:706207. doi: 10.3389/fmicb.2021.706207. eCollection 2021.

ABSTRACT

Chronic pulmonary infections caused by non-tuberculous mycobacteria of the Mycobacterium abscessus complex (MABSC) are emerging as a global health problem and pose a threat to susceptible individuals with structural lung disease such as cystic fibrosis. The molecular mechanisms underlying the pathogenicity and intrinsic resistance of MABSC to antibiotics remain largely unknown. The involvement of Msp-type porins in the virulence and biocide resistance of some rapidly growing non-tuberculous mycobacteria and the finding of deletions and rearrangements in the porin genes of serially collected MABSC isolates from cystic fibrosis patients prompted us to investigate the contribution of these major surface proteins to MABSC infection. Inactivation by allelic replacement of the each of the two Msp-type porin genes of M. abscessus subsp. massiliense CIP108297, mmpA and mmpB, led to a marked increase in the virulence and pathogenicity of both mutants in murine macrophages and infected mice. Neither of the mutants were found to be significantly more resistant to antibiotics. These results suggest that adaptation to the host environment rather than antibiotic pressure is the key driver of the emergence of porin mutants during infection.

PMID:34335541 | PMC:PMC8317493 | DOI:10.3389/fmicb.2021.706207

J Dev Behav Pediatr. 2021 Jul 29. doi: 10.1097/DBP.0000000000000967. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to examine the moderating role of resilience in the relationship between sense of stress and posttraumatic growth (PTG) in mothers of children with cystic fibrosis (CF).

METHODS: This cross-sectional study was conducted in a group of 139 mothers of children with CF. A diagnostic survey with Polish versions of the inventories was used.

RESULTS: Over half of the mothers (52.89%) reported average and 26.11% high levels of general sense of stress. Mothers also experienced high (37.68%) and average (34.06%) PTG. Generally, mothers of children with CF manifested low general resilience. Sense of stress and PTG were significantly and positively correlated in this group of mothers. Positive correlations were revealed between resilience (total and individual dimensions), total PTG, and 1 dimension of PTG: changes in self-perception. Moreover, resilience was found to correlate with sense of stress. The obtained results indicate that resilience manifested as an optimistic life attitude and the ability to mobilize in difficult situations, and tolerance of failures and treating life as a challenge is a moderator in the relationship between sense of stress and PTG.

CONCLUSION: The relationship between sense of stress and PTG in mothers of children with CF depends on the level of resilience.

PMID:34334723 | DOI:10.1097/DBP.0000000000000967

Zhonghua Er Ke Za Zhi. 2021 Aug 2;59(8):689-694. doi: 10.3760/cma.j.cn112140-20210112-00033.

ABSTRACT

Objective: To analyze the cystic fibrosis transmembrane conductance regulator (CFTR) gene variations and phenotypes in 7 Chinese children. Methods: In this retrospective study, the data of 7 children with CFTR gene variations admitted to Children's Hospital of Chongqing Medical University from December 2013 to October 2020 were extracted. The general information, clinical manifestations, gene variations, diagnosis and treatment were summarized. Results: Among the 7 children, 2 were males and 5 were females, aged 5.2(0.5-11.3) years. Main clinical manifestations included malnutrition (5 cases), recurrent respiratory infection (4 cases), bronchiectasis (3 cases), steatorrhea (3 cases), vomiting in infancy (2 cases), liver cirrhosis (2 cases), meconium ileus (1 case), metabolic alkalosis and hypochloremia (1 case). A total of 15 variations were found by whole exon sequencing and Sanger sequencing, among which 3 were newly discovered, and 7 were missense mutations. Four children were diagnosed as CF, and the other 3 were diagnosed as CFTR related disease (CFTR-RD). Compared with CF patients, the pancreatic insufficiency and typical CF lung disease were relatively mild in CFTR-RD patients. After treatment, 6 children were clinically improved, while the rest one withdrew treatment due to critical pulmonary infection and disturbance of water-electrolyte metabolism. Conclusions: The loci and phenotypes of CFTR gene variants vary hugely and the pathogenicity of some variations are not clear. Whole exon sequencing can facilitate the identification of CF-and CFTR-RD-causing variaions. For the cases not compatible with CF, CFTR-RD should be considered and evaluated by timely gene detection, so as to carry out appropriate long term management.

PMID:34333923 | DOI:10.3760/cma.j.cn112140-20210112-00033