Publications by authors named "Michael Edwards"

631 Publications

Racial disparity in causes for readmission following bariatric surgery.

Surg Obes Relat Dis 2021 Oct 27. Epub 2021 Oct 27.

Division of Health Care Delivery Research, Mayo Clinic, Jacksonville, Florida.

Background: Readmission after bariatric surgery is not cost-effective and is a preventable quality metric within standardized practices. However, reasons for readmission among racial/ethnic bariatric cohorts are less explored and understood.

Objective: Our study objective was designed to compare reasons for readmission among racial/ethnic cohorts of bariatric patients.

Setting: Academic hospital.

Methods: We performed a retrospective analysis of the 2015-2018 MBSAQIP databases to identify Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) cases. Regression analyses determined predictors of all-cause and bariatric-related readmissions. Reasons for readmission were compared between racial/ethnic cohorts using propensity score matching.

Results: More than 550 000 RYGB and SG cases were analyzed. The readmission rate was 3%-4%. Black race, RYGB, robot-assisted approach, and numerous co-morbidities were independently associated with readmission (P <.05). In RYGB cases, black (versus white) patients were at decreased odds of leak-related (P < .001) and cardiovascular-related (P < .001) readmissions but at increased odds of readmissions related to renal complications (P < .001). Hispanic (versus white) patients had a higher likelihood of venous thromboembolism-related readmissions (P < .001). In SG cases, black (versus white) patients had a similar lower likelihood of readmission related to leaks or cardiovascular complications but higher odds of readmission related to renal complications (P < .001). Hispanic (versus black) patients had a higher likelihood of leak-related readmissions (P < .001).

Conclusion: Readmission reasons after bariatric surgery vary by race/ethnicity. Perioperative pathways to mitigate complications, including readmissions, should consider these disparate findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2021.10.015DOI Listing
October 2021

Characterization of polycyclic aromatic hydrocarbons in the Great Lakes Basin using dreissenid mussels.

Environ Monit Assess 2021 Nov 20;193(12):833. Epub 2021 Nov 20.

National Ocean Service, National Oceanic and Atmospheric Administration, National Centers for Coastal Ocean Science, 1305 East West Highway, Silver Spring, N/SCI1MD, 20910, USA.

The National Oceanic and Atmospheric Administration (NOAA), National Centers for Coastal Ocean Science (NCCOS) Mussel Watch Program (MWP), conducts basin-wide monitoring and place-based assessments using dreissenid mussels as bioindicators of chemical contamination in the Laurentian Great Lakes. Polycyclic aromatic hydrocarbons (PAHs) body burden results for the period 2009-2018 were combined into one dataset from multiple MWP studies allowing for a robust characterization of PAH contamination. Patterns in PAH data were identified using descriptive statistics and machine learning techniques. Relationships between total PAH concentration in dreissenid mussel tissue, impervious surface percentages, and PAH relative concentration were identified and used to build a predictive model for the Great Lakes Basin. Significant positive correlation was identified by the Spearman's rank correlation test between total PAH concentration and percent impervious surface. The findings support the paradigm that PAHs are primarily derived from land-based sources. Offshore and riverine locations had the lowest and highest median total PAH concentrations, respectively. PAH assemblages and ratios indicated that pyrogenic sources were more predominant than petrogenic sources and that PAHs at offshore sites exhibited relatively more weathering compared to inshore sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10661-021-09401-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604852PMC
November 2021

Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial.

Thorax 2021 Oct 29. Epub 2021 Oct 29.

Guy's Severe Asthma Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background And Aims: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.

Methods: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.

Results: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.

Conclusion: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2021-217429DOI Listing
October 2021

Measuring treatment response to advance precision medicine for multiple sclerosis.

Ann Clin Transl Neurol 2021 Nov 26;8(11):2166-2173. Epub 2021 Oct 26.

Biogen, Cambridge, Massachusetts, USA.

Objective: To assess the independent contributions of clinical measures (relapses, Expanded Disability Status Scale [EDSS] scores, and neuroperformance measures) and nonclinical measures (new brain magnetic resonance imaging [MRI] activity and serum neurofilament light chain [sNfL] levels) for distinguishing natalizumab-treated from placebo-treated patients.

Methods: We conducted post hoc analyses using data from the AFFIRM trial of natalizumab for multiple sclerosis. We used multivariable regression analyses with predictors (EDSS progression, no relapse, new or enlarging MRI activity, brain atrophy, sNfL levels, and neuroperformance worsening) to identify measures that independently discriminated between treatment groups.

Results: The multivariable model that best distinguished natalizumab from placebo was no new or enlarging T2 or gadolinium-enhancing activity on MRI (odds ratio; 95% confidence interval: 7.2; 4.7-10.9), year 2 sNfL levels <97.5th percentile (4.1; 2.6-6.2), and no relapses in years 0-2 (2.1; 1.5-3.0). The next best-fitting model was a two-component model that included no MRI activity and sNfL levels <97.5th percentile at year 2. There was little difference between the three- and two-component models.

Interpretation: Nonclinical measures (new MRI activity and sNfL levels) discriminate between treatment and placebo groups similarly to or better than clinical outcomes composites and have implications for patient monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607451PMC
November 2021

Implementation of a Multi-Modal Training Program for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings: Pathways to Comorbidity Care (PCC).

J Dual Diagn 2021 Oct-Dec;17(4):304-312. Epub 2021 Oct 26.

Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, Australia.

Objectives: We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drugs (AOD) clinicians to improve the management of comorbidity.

Methods: A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined (a) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice ( = 10 clinical files per clinician), (b) self-efficacy, knowledge, and attitudes of clinicians.

Results: Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v -12% change from baseline, respectively; [ (1,  = 340) = 35.29, = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [ (1,  = 340) = 10.45, = .06]. There were significant improvements in the PCC relative to the control group for clinician self-efficacy, (1,33) = 6.40, = .02 and knowledge and attitudes of comorbidity monitoring, (1,33) = 8.745, = .01.

Conclusions: The PCC training package may help improve identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity in drug and alcohol settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15504263.2021.1984152DOI Listing
October 2021

Racial disparities in bariatric perioperative outcomes among the elderly.

Surg Obes Relat Dis 2021 Sep 29. Epub 2021 Sep 29.

Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania.

Background: Bariatric surgery outcomes in elderly patients have been shown to be safe, but with a higher rate of adverse outcomes compared with nonelderly patients. The impact of race on bariatric surgery outcomes continues to be explored, with recent studies showing higher rates of adverse outcomes in black patients. Perioperative outcomes in racial cohorts of elderly bariatric patients are largely unexplored.

Objective: The goal of this study was to compare outcomes between elderly non-Hispanic black (NHB) and non-Hispanic white (NHW) bariatric surgery patients to determine whether outcomes are mediated by race.

Setting: Academic hospital.

Methods: Patients who had a primary Roux-en-Y (RYGB) and sleeve gastrectomy (SG) in the period 2015-2018 and were at least 65 years of age were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use Data File (MBSAQIP PUF). Selected cases were stratified by race. Outcomes were compared between matched racial cohorts. Multivariate regression analyses were performed to determine whether race independently predicted morbidity.

Results: From 2015 to 2018, 29,394 elderly NHW (90.8%) and NHB (9.2%) patients underwent an RYGB or SG. At baseline, NHB elderly patients had a higher burden of co-morbid conditions, resulting in higher rates of overall (7.7% versus 6.4%, P = .009) and bariatric-related (5.4% versus 4.1%, P = .001) morbidity. All outcome measures were similar between propensity-score-matched racial elderly bariatric patient cohorts. On regression analysis, NHB race remained independently correlated with morbidity (odds ratio [OR] 1.3, 95% CI 1.08-1.47, P = .003).

Conclusion: RYGB and SG are safe in elderly patient cohorts, with no differences in adverse outcomes between NHB and NHW patients, accounting for confounding factors. While race does not appear to impact outcomes in the elderly cohorts, NHB race may play a role in access.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2021.09.012DOI Listing
September 2021

What Sets Physically Active Rural Communities Apart from Less Active Ones? A Comparative Case Study of Three US Counties.

Int J Environ Res Public Health 2021 10 9;18(20). Epub 2021 Oct 9.

Department of Public Administration, West Virginia University, Morgantown, WV 26506, USA.

Background: Rural US communities experience health disparities, including a lower prevalence of physical activity (PA). However, "Positive Deviants"-rural communities with greater PA than their peers-exist. The purpose of this study was to identify the factors that help create physically active rural US communities.

Methods: Stakeholder interviews, on-site intercept interviews, and in-person observations were used to form a comparative case study of two rural counties with high PA prevalence (HPAs) and one with low PA prevalence (LPA) from a southern US state, selected based on rurality and adult PA prevalence. Interview transcripts were inductively coded by three readers, resulting in a thematic structure that aligned with a Community Capital Framework, which was then used for deductive coding and analysis.

Results: Fifteen stakeholder interviews, nine intercept interviews, and on-site observations were conducted. Human and Organizational Capital differed between the HPAs and LPA, manifesting as Social, Built, Financial, and Political Capital differences and a possible "spiraling-up" or cyclical effect through increasing PA and health (Human Capital), highlighting a potential causal model for future study.

Conclusions: Multi-organizational PA coalitions may hold promise for rural PA by directly influencing Human and Organizational Capital in the short term and the other forms of capital in the long term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph182010574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535724PMC
October 2021

Collaborative care: Primary health workforce and service delivery in Western New South Wales-A case study.

Aust J Rural Health 2021 Oct 29;29(5):768-778. Epub 2021 Sep 29.

NSW Rural Doctors Network, Newcastle, NSW, Australia.

Objective: To explore how four small towns in rural New South Wales known as the 4Ts are addressing challenges accessing quality care and sustainable health services through a collaborative approach to workforce planning using the collaborative care framework.

Design: Descriptive case study approach.

Setting: The collaborative care project was developed as a result of ongoing partnerships between 2 rural Local Health Districts, 2 Primary Health Networks and a non-governmental health workforce organisation. The collaboration works with 5 subregions each comprising 2 or more rural communities. This paper focuses on the 4Ts subregion.

Participants: Stakeholders of the collaborative design including organisations and the community.

Intervention: A place-based approach to co-designing health services with community in one sub-region of Western New South Wales.

Main Outcome Measures: A synthesis of field observations and experiences of community and jurisdictional partners in implementation of the 4Ts subregional model. Mapping of implementation processes against the collaborative care framework.

Results: The collaborative care framework is a useful planning and community engagement tool to build health workforce literacy and to impact on system change at the local level. We identify key elements of effectiveness in establishing the 4Ts model, including the need for coordinated health system planning, better integrating existing resources to deliver services, community engagement, building health workforce literacy and town-based planning.

Conclusion: This study adds to the body of knowledge about how to successfully develop a collaborative primary health care workforce model in practice. The findings demonstrate that the implementation of a collaborative primary health care workforce model using the collaborative care framework can improve service access and quality, which in turn might facilitate workforce sustainability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajr.12796DOI Listing
October 2021

Operative Fixation of Lateral Malleolus Fractures With Locking Plates vs Nonlocking Plates: A Systematic Review and Meta-analysis.

Foot Ankle Int 2021 Sep 28:10711007211040508. Epub 2021 Sep 28.

Department of Trauma Surgery, Radboud University Medical Center, Nijmegen, Nijmegen, the Netherlands.

Background: The exact benefit of locking plates over nonlocking plates in patients with lateral malleolus fractures remains unclear. The primary aim of this study was to compare the functional outcome of locking plates vs nonlocking plates in patients with a lateral malleolus fracture. The secondary aims were to compare the number of complications and hardware removals and to compare whether results differed for older patients and for patients treated with anatomical locking plates.

Methods: The PubMed/MEDLINE, Embase, Cochrane, and CINAHL databases were searched for studies comparing locking plates with nonlocking plates in patients with fixated lateral malleolus fractures. All included studies were assessed on their methodologic quality using the MINORS. Subgroup analyses were performed on older patients and patients treated with anatomical locking plates.

Results: A total of 11 studies were included. The meta-analysis showed that functional outcome did not differ between patients treated with locking plates and nonlocking plates (MD 2.38, 95% CI -2.71 to 7.46). No difference in both complication rate (OR 1.10, 95% CI 0.74-1.63) and the amount of hardware removals (OR 0.77, 95% CI 0.52-1.14) was found. Even after analyzing older patients and patients treated with anatomical locking plates, no benefit was shown.

Conclusion: This meta-analysis demonstrates no clear benefit in selecting locking plates over nonlocking plates in the treatment of lateral malleolus fractures.

Clinical Relevance: Locking plates are increasingly being used in the treatment of lateral malleolus fractures. Biomechanical studies have shown an increased stability with use of locking vs nonlocking plates. This clinical review does not support a benefit of use of locking plates for these fractures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10711007211040508DOI Listing
September 2021

Cast-OFF Trial: One Versus 4 to 5 Weeks of Plaster Cast Immobilization for Nonreduced Distal Radius Fractures: A Randomized Clinical Feasibility Trial.

Hand (N Y) 2021 Sep 27:15589447211044775. Epub 2021 Sep 27.

Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Distal radius fracture is a common fracture of which the incidence appears to be increasing worldwide. This pilot study investigated whether 1 week of plaster cast is feasible for nonreduced (stable fractures including nondisplaced and displaced fractures) distal radius fractures.

Methods: The study was a multicenter randomized clinical feasibility trial including patients from regional acute care providers. Patients with a nonreduced distal radius fracture were included in the study. Nonreduced fractures meant intra-articular or extra-articular fractures and including nondisplaced and minimal displaced fractures (dorsal angulation less than 5°-10°, maximum radial shortening of 2 mm, and maximum radial shift of 2 mm) not needing a reduction. Forty Patients were included and randomized. After 1 week of plaster cast, patients were randomized to 1 of the 2 treatment groups: plaster cast removed (intervention group) versus 4 to 5 weeks of plaster cast (control group).

Results: The analysis shows no significant differences between the 2 groups in having less pain, better function after 6 weeks, and better overall patient satisfaction. No difference was shown in secondary displacement between the 2 groups (control 1 vs intervention 0).

Conclusion: One week of plaster cast treatment for nonreduced distal radius fracture is feasible, preferred by patients, with at least the same functional outcome and pain scores.

Level Of Evidence: According to the Oxford 2011 level of evidence, the level of evidence of this study is 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15589447211044775DOI Listing
September 2021

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 3;PP. Epub 2021 Sep 3.

New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely non-invasive, non-thermal, and non-ionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image-guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant pre-clinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TUFFC.2021.3110083DOI Listing
September 2021

Pulmonary Innate Lymphoid Cell Responses during Rhinovirus-induced Asthma Exacerbations : A Clinical Trial.

Am J Respir Crit Care Med 2021 Dec;204(11):1259-1273

National Heart and Lung Institute, London, United Kingdom.

Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well characterized. To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects. Patients with moderate asthma and healthy subjects were inoculated with rhinovirus-16 and underwent bronchoscopy at baseline and at Day 3, and Day 8 after inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage using flow cytometry. The ratio of bronchoalveolar lavage ILC2:ILC1 was assessed to determine their relative contributions to the clinical and immune response to rhinovirus challenge. At baseline, ILC2s were significantly higher in patients with asthma than in healthy subjects. At Day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in patients with asthma than in healthy subjects (all comparisons  < 0.05). In healthy subjects, ILC1s increased from baseline at Day 3 ( = 0.001), while in patients with asthma, ILC1s increased from baseline at Day 8 ( = 0.042). Patients with asthma had significantly higher ILC2:ILC1 ratios at baseline ( = 0.024) and Day 8 ( = 0.005). Increased ILC2:ILC1 ratio in patients with asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid. An ILC2-predominant inflammatory profile in patients with asthma was associated with increased severity and duration of rhinovirus infection compared with healthy subjects, supporting the potential role of ILC2s in the pathogenesis of virus-induced asthma exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202010-3754OCDOI Listing
December 2021

Age-dependent Intracranial Artery Morphology in Healthy Children.

Clin Neuroradiol 2021 Aug 24. Epub 2021 Aug 24.

Department of Radiology, Faculty of Medicine, University of Calgary, HMRB Building, Room 155, 3330 Hospital Drive NW, AB T2N 4N1, Calgary, Canada.

Purpose: Evaluation of intracranial artery morphology plays an important role in diagnosing a variety of neurovascular diseases. In addition to clinical symptoms, diagnosis currently relies on qualitative rather than quantitative evaluation of vascular imaging sequences, such as magnetic resonance angiography (MRA). However, there is a paucity of literature on normal arterial morphology in the pediatric population across brain development. We aimed to quantitatively assess normal, age-related changes in artery morphology in children.

Methods: We performed retrospective analysis of pediatric MRA data obtained from a tertiary referral center. An MRA dataset from 98 children (49 boys/49 girls) aged 0.6-20 years (median = 11.5 years) with normal intracranial vasculature was retrospectively collected between 2011 and 2018. All arteries were automatically segmented to determine the vessel radius. Using an atlas-based approach, the average radius and density of arteries were measured in the three main cerebral vascular territories and the radius of five major arteries was determined at corresponding locations.

Results: The radii of the major arteries as well as the average artery radius and density in the different vascular territories in the brain remained constant throughout childhood and adolescence (|r| < 0.369 in all cases).

Conclusion: This study presents the first automated evaluation of intracranial vessel morphology on MRA across childhood. Our results can serve as a framework for quantitative evaluation of cerebral vessel morphology in the setting of pediatric neurovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00062-021-01071-9DOI Listing
August 2021

Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection.

Am J Respir Crit Care Med 2021 11;204(9):1075-1085

Department of Surgery and Cancer.

Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation triggers is important to guide appropriate therapy, but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection etiology. To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. We used serial sampling within and studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas chromatography-mass spectrometry techniques were used to measure VOC production from infected airway epithelial-cell cultures and in exhaled breath samples from healthy subjects experimentally challenged with rhinovirus (RV)-A16 and from subjects with COPD with naturally occurring exacerbations. We identified a novel VOC signature comprising decane and other long-chain alkane compounds that is induced during RV infection of cultured airway epithelial cells and is also increased in the exhaled breath from healthy subjects experimentally challenged with RV and from patients with COPD during naturally occurring viral exacerbations. These compounds correlated with the magnitude of antiviral immune responses, viral burden, and exacerbation severity but were not induced by bacterial infection, suggesting that they represent a specific virus-inducible signature. Our study highlights the potential for measurement of exhaled breath VOCs as rapid, noninvasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202103-0660OCDOI Listing
November 2021

Objective Assessment of Physical Activity and Associated Contexts During High School Sport Practices.

Front Sports Act Living 2021 9;3:548516. Epub 2021 Jul 9.

North Carolina State University, Raleigh, NC, United States.

Organized sports provide children and adolescents with opportunities to achieve recommended amounts of moderate to vigorous physical activity (MVPA), and schools are a primary setting for sports programs. The main aims of this study were to examine participant physical activity (PA) levels during the most popular high school sports in the United States and to assess the influences of practice contextual factors on PA levels. Participant PA and its contexts were assessed during practices for the 10 most popular girls' and boys' high school sports in the United States. Data were obtained during 598 practice sessions in 12 schools in North Carolina using a validated direct observation instrument (System for Observing Fitness Instruction Time (SOFIT). A regression model was applied to understand the association between sport context and athletes' PA. Overall, athletes were observed engaging in MVPA 60% of practice time. MVPA varied among sports and levels were highly influenced by practice contexts. Among girls' sports, cross country and soccer practices provided the highest proportion of MVPA and MVPA percent during boys' practice sessions was highest during cross country and track and field. Practice contexts were associated with MVPA accrual with time allocated for gameplay and fitness activities associated with the highest levels of PA. The results contribute to an understanding of which sports and how their practices are conducted facilitate increased PA. Findings indicate athletes accrue substantial amounts of PA during high school practices, but that it varies from sport to sport. As well, the context that characterizes sport practices is a significant determinant in how much PA occurs. Most sports that emphasized game simulation, fitness, and skill development drills had higher levels of MVPA. Given the length and frequency of practices and how the content is delivered, we can accurately predict how much PA athletes are likely to achieve during a given sport season. The findings from this study demonstrate that sport can make a useful, if not sufficient role in helping high school athletes reach recommended PA levels. PA engagement can be optimized by attending to the management of contexts surrounding the sports.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fspor.2021.548516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299060PMC
July 2021

Environmental Factors Associated with Physical Activity in Rural U.S. Counties.

Int J Environ Res Public Health 2021 07 20;18(14). Epub 2021 Jul 20.

US Department of Agriculture, Agricultural Research Service, Grand Forks, ND 58201, USA.

Background: Rural U.S. adults' prevalence of meeting physical activity (PA) guidelines is lower than urban adults, yet rural-urban differences in environmental influences of adults' PA are largely unknown. The study's objective was to identify rural-urban variations in environmental factors associated with the prevalence of adults meeting PA guidelines.

Methods: County-level data for non-frontier counties ( = 2697) were used. A five-category rurality variable was created using the percentage of a county's population living in a rural area. Factor scores from Factor Analyses (FA) were used in subsequent Multiple Linear Regression (MLR) analyses stratified by rurality to identify associations between environmental factor scores and the prevalence of males and females meeting PA guidelines.

Results: FA revealed a 13-variable, four-factor structure of natural, social, recreation, and transportation environments. MLR revealed that natural, social, and recreation environments were associated with PA for males and females, with variation by sex for social environment. The natural environment was associated with PA in all but urban counties; the recreation environment was associated with PA in the urban counties and the two most rural counties.

Conclusions: Variations across the rural-urban continuum in environmental factors associated with adults' PA, highlight the uniqueness of rural PA and the need to further study what succeeds in creating active rural places.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18147688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307667PMC
July 2021

A New Look at an Old Problem: Improving Diversity, Equity, and Inclusion in Scientific Research.

Am Surg 2021 Nov 12;87(11):1722-1726. Epub 2021 Jul 12.

Department of Surgery, 12280Wake Forest School of Medicine, Winston-Salem, NC, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/00031348211029853DOI Listing
November 2021

Antimicrobial coating prevents ventilator-associated pneumonia in a 72 hour large animal model.

J Surg Res 2021 Jul 3;267:424-431. Epub 2021 Jul 3.

Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

Background: The primary goal of this study was to demonstrate that endotracheal tubes coated with antimicrobial lipids plus mucolytic or antimicrobial lipids with antibiotics plus mucolytic would significantly reduce pneumonia in the lungs of pigs after 72 hours of continuous mechanical ventilation compared to uncoated controls.

Materials And Methods: Eighteen female pigs were mechanically ventilated for up to 72 hours through uncoated endotracheal tubes, endotracheal tubes coated with the antimicrobial lipid, octadecylamine, and the mucolytic, N-acetylcysteine, or tubes coated with octadecylamine, N-acetylcysteine, doxycycline, and levofloxacin (6 pigs per group). No exogenous bacteria were inoculated into the pigs, pneumonia resulted from the pigs' endogenous oral flora. Vital signs were recorded every 15 minutes and arterial blood gas measurements were obtained for the duration of the experiment. Pigs were sacrificed either after completion of 72 hours of mechanical ventilation or just prior to hypoxic arrest. Lungs, trachea, and endotracheal tubes were harvested for analysis to include bacterial counts of lung, trachea, and endotracheal tubes, lung wet and dry weights, and lung tissue for histology.

Results: Pigs ventilated with coated endotracheal tubes were less hypoxic, had less bacterial colonization of the lungs, and survived significantly longer than pigs ventilated with uncoated tubes. Octadecylamine-N-acetylcysteine-doxycycline-levofloxacin coated endotracheal tubes had less bacterial colonization than uncoated or octadecylamine-N-acetylcysteine coated tubes.

Conclusion: Endotracheal tubes coated with antimicrobial lipids plus mucolytic and antimicrobial lipids with antibiotics plus mucolytic reduced bacterial colonization of pig lungs after prolonged mechanical ventilation and may be an effective strategy to reduce ventilator-associated pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2021.05.046DOI Listing
July 2021

Catastrophic bilateral sudden sensorineural hearing loss following COVID-19.

BMJ Case Rep 2021 Jun 24;14(6). Epub 2021 Jun 24.

Department of Otolaryngology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Since December 2019, when it was first detected in Wuhan, the SARS-CoV-2 (COVID-19) has spread across the globe. The pandemic has had an unprecedented impact on the global population with >110 million confirmed cases and 2.5 million deaths. The most common initial symptoms of COVID-19 infection are cough, dyspnoea, fever, malaise and anosmia. Severe clinical manifestations include respiratory compromise, pneumonia, organ failure and death. There have been many other less common symptoms as a result of COVID-19 described in the literature, including significant rates of olfactory dysfunction. However, we believe there has been only one other previously documented cases of bilateral hearing loss.Sudden sensorineural hearing loss is a relatively common presentation seen by otolaryngologists. It is defined as rapid hearing loss, ≥30 dB occurring over 3 consecutive days in three contiguous sound frequencies. The exact pathological process is yet to be fully characterised, though it is most commonly unilateral and commonly develops shortly following viral infection. Treatment typically consists of glucocorticoid steroids administered orally, via intratympanic injection or a combination of both routes though there are currently no standardised management of these patients.Bilateral sudden sensorineural hearing loss (SSNHL) is rare, accounting for <2% of all cases. We describe a case of bilateral SSNHL in a 68-year-old patient who presented with profound hearing loss shortly after symptomatic infection with COVID-19, which at the time of publication is the first such case reported in the literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2021-243157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230962PMC
June 2021

Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials.

Health Qual Life Outcomes 2021 Jun 13;19(1):164. Epub 2021 Jun 13.

Duke University School of Medicine, Durham, NC, USA.

Objectives: There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge.

Methods: Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States.

Results: Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims.

Conclusions: A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12955-021-01800-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201736PMC
June 2021

Design recommendations for exoskeletons: Perspectives of individuals with spinal cord injury.

J Spinal Cord Med 2021 Jun 1:1-6. Epub 2021 Jun 1.

Department of Trauma Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.

Objective: This study investigated the expectations of individuals with spinal cord injury (SCI) regarding exoskeletons.

Design: The survey consisted out of questions regarding multiple aspects of exoskeleton technology.

Setting: An online survey was distributed via the monthly newsletter of the Dutch Patient Association for Spinal Cord Injury (SCI).

Participants: Individuals with SCI who are members of the Dutch Patient Association for SCI.

Outcome Measures: General impression of exoskeleton technology, expectations regarding capabilities and user-friendliness, training expectations and experiences, future perspectives and points of improvement.

Results: The survey was filled out by 95 individuals with SCI, exoskeletons were considered positive and desirable by 74.7%. About 11 percent (10.5%) thought one could ambulate faster, or just as fast, while wearing an exoskeleton as able-bodied people. Furthermore, 18.9% expected not to use a wheelchair or walking aids while ambulating with the exoskeleton. Twenty-five percent believed that exoskeletons could replace wheelchairs. Some main points of improvement included being able to wear the exoskeleton in a wheelchair and while driving a car, not needing crutches while ambulating, and being able to put the exoskeleton on by oneself.

Conclusion: Individuals with SCI considered exoskeletons as a positive and desirable innovation. But based on the findings from the surveys, major points of improvement are necessary for exoskeletons to replace wheelchairs in the future. For future exoskeleton development, we recommend involvement of individuals with SCI to meet user expectations and improve in functionality, usability and quality of exoskeletons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10790268.2021.1926177DOI Listing
June 2021

Dutch trauma system performance: Are injured patients treated at the right place?

Injury 2021 Jul 16;52(7):1688-1696. Epub 2021 May 16.

Brabant Trauma Registry, Network Emergency Care Brabant, Tilburg, the Netherlands.

Background: The goal of trauma systems is to match patient care needs to the capabilities of the receiving centre. Severely injured patients have shown better outcomes if treated in a major trauma centre (MTC). We aimed to evaluate patient distribution in the Dutch trauma system. Furthermore, we sought to identify factors associated with the undertriage and transport of severely injured patients (Injury Severity Score (ISS) >15) to the MTC by emergency medical services (EMS).

Methods: Data on all acute trauma admissions in the Netherlands (2015-2016) were extracted from the Dutch national trauma registry. An ambulance driving time model was applied to calculate MTC transport times and transport times of ISS >15 patients to the closest MTC and non-MTC. A multivariable logistic regression analysis was performed to identify factors associated with ISS >15 patients' EMS undertriage to an MTC.

Results: Of the annual average of 78,123 acute trauma admissions, 4.9% had an ISS >15. The nonseverely injured patients were predominantly treated at non-MTCs (79.2%), and 65.4% of patients with an ISS >15 received primary MTC care. This rate varied across the eleven Dutch trauma networks (36.8%-88.4%) and was correlated with the transport times to an MTC (Pearson correlation -0.753, p=0.007). The trauma networks also differed in the rates of secondary transfers of ISS >15 patients to MTC hospitals (7.8% - 59.3%) and definitive MTC care (43.6% - 93.2%). Factors associated with EMS undertriage of ISS >15 patients to the MTC were female sex, older age, severe thoracic and abdominal injury, and longer additional EMS transport times.

Conclusions: Approximately one-third of all severely injured patients in the Netherlands are not initially treated at an MTC. Special attention needs to be directed to identifying patient groups with a high risk of undertriage. Furthermore, resources to overcome longer transport times to an MTC, including the availability of ambulance and helicopter services, may improve direct MTC care and result in a decrease in the variation of the undertriage of severely injured patients to MTCs among the Dutch trauma networks. Furthermore, attention needs to be directed to improving primary triage guidelines and instituting uniform interfacility transfer agreements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.injury.2021.05.015DOI Listing
July 2021

Heavy drinking as phenomenon: gender and agency in accounts of men's heavy drinking.

Health Sociol Rev 2020 Dec 9:1-16. Epub 2020 Dec 9.

Australian Research Centre in Sex Health and Society, La Trobe University, Melbourne, Australia.

Alcohol consumption is a significant public health concern in Australia, with men disproportionately represented in treatment for health issues related to heavy drinking. Despite this, little is known about the experiences of these men or the gender dynamics that may shape heavy drinking. Increasingly, the treatment of alcohol and other drug-related issues, including those related to heavy drinking, is based on a biopsychosocial approach. Within this framework, heavy drinking is understood as a symptom of individual pathology in the context of various social 'factors' that influence individual capacity to exercise agency. Following the work of Karen Barad, this article employs a feminist science studies account of agency to formulate heavy drinking as a gendered 'phenomenon': enacted and sustained through the 'intra-action' of other phenomena. Drawing on interviews with men who drink heavily, our analysis explores how the phenomenon of men's heavy drinking materialises through the intra-actions of gender, isolation and healthcare. We argue that heavy drinking is not a sign of failed individual agency but an expression of entangled agencies. In concluding, we suggest it is possible to enhance the well-being of men who drink heavily by addressing specific gendered intra-actions in the making of heavy drinking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14461242.2020.1850317DOI Listing
December 2020

Basic care as exceptional care: addiction stigma and consumer accounts of quality healthcare in Australia.

Health Sociol Rev 2021 07 9;30(2):95-110. Epub 2020 Jul 9.

Centre for Social Research in Health, Faculty of Arts and Social Sciences, University of New South Wales, Australia.

The discrimination faced by people understood to have alcohol or other drug addictions has been the subject of extensive research, with many studies documenting experiences of stigma within healthcare services. Building on this literature, we examine the role of stigma in shaping the healthcare expectations of people seen as affected by alcohol and other drug addictions. Our analysis draws on recent theorisations of stigma as a process of social production to analyse in-depth, qualitative interviews with 20 people who had recently attended an inpatient withdrawal management service. Participants describe as exceptional forms of care that are often taken for granted by other members of the community. We argue that routinised experiences of discrimination work to constitute basic care as exceptional. This finding is significant for two reasons: (1) people who consume alcohol and other drugs often have complex healthcare needs and already encounter obstacles to accessing the care they need, and (2) by positioning people who consume drugs outside the purview of healthcare, this dynamic obstructs their fundamental right to care. We conclude by reflecting on the implications of these findings for those who are often positioned as not entitled to high quality healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14461242.2020.1789485DOI Listing
July 2021

The Poor Fit of Model Fit for Selecting Number of Factors in Exploratory Factor Analysis for Scale Evaluation.

Educ Psychol Meas 2021 Jun 12;81(3):413-440. Epub 2020 Aug 12.

Arizona State University, Tempe, AZ, USA.

Model fit indices are being increasingly recommended and used to select the number of factors in an exploratory factor analysis. Growing evidence suggests that the recommended cutoff values for common model fit indices are not appropriate for use in an exploratory factor analysis context. A particularly prominent problem in scale evaluation is the ubiquity of correlated residuals and imperfect model specification. Our research focuses on a scale evaluation context and the performance of four standard model fit indices: root mean square error of approximate (RMSEA), standardized root mean square residual (SRMR), comparative fit index (CFI), and Tucker-Lewis index (TLI), and two equivalence test-based model fit indices: RMSEAt and CFIt. We use Monte Carlo simulation to generate and analyze data based on a substantive example using the positive and negative affective schedule ( = 1,000). We systematically vary the number and magnitude of correlated residuals as well as nonspecific misspecification, to evaluate the impact on model fit indices in fitting a two-factor exploratory factor analysis. Our results show that all fit indices, except SRMR, are overly sensitive to correlated residuals and nonspecific error, resulting in solutions that are overfactored. SRMR performed well, consistently selecting the correct number of factors; however, previous research suggests it does not perform well with categorical data. In general, we do not recommend using model fit indices to select number of factors in a scale evaluation framework.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0013164420942899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072951PMC
June 2021

Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells.

J Biol Chem 2021 Jan-Jun;296:100701. Epub 2021 Apr 23.

Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany; Department of Surgery, Medical School, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address:

The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062550PMC
July 2021

Comparison of eGFR formulas in determining chronic kidney disease stage in bariatric patients and the impact on perioperative outcomes.

Surg Obes Relat Dis 2021 Jul 19;17(7):1317-1326. Epub 2021 Mar 19.

Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania.

Background: Chronic kidney disease (CKD) independently increases the risk of 30-day adverse outcomes following metabolic and bariatric surgery (MBS). However, no studies have evaluated the stage of CKD at which increased perioperative risk is manifested. Here, we correlate 30-day major morbidities after MBS with extent of renal disease based on CKD Stage.

Objectives: To determine the impact of CKD stage on perioperative outcomes after bariatric surgery.

Setting: Academic Hospital.

Methods: From the 2017 Metabolic and Bariatric Surgery Quality Improvement Program (MBSAQIP) database, we identified patients with CKD who underwent sleeve gastrectomy or laparoscopic gastric bypass surgery. Glomerular filtration rates (GFRs) were calculated and cohorts were generated based on CKD Stage. Complication rates and rates of morbidity and mortality were compared between stages, and strengths of correlation were calculated.

Results: GFR and CKD Stage were calculated for 150,283 patients. There was a significant increase in the risk of major morbidity at each progressive stage of CKD (P < .001 for all compared stages). There was a strong positive linear correlation between increasing CKD Stage and total morbidity (r = .983), including reoperation ( r = .784), readmission (r = .936), unplanned ICU transfer (r = .853), and aggregate complications such as pulmonary (r = .900), bleeding (r = .878), or progressive worsening of renal function (r = .845). In logistic regression, for every 10-point decrease in GFR, odds of total morbidity increased by 6%.

Conclusion: An increased risk of perioperative complications may be seen in early stages of CKD, and risk is compounded in more advanced stages. Bariatric surgical candidates should be counseled on their increased risk of surgical complications even with mild CKD, and the benefits of bariatric surgery should be carefully weighed against significantly increased risks of complications in severe CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2021.03.006DOI Listing
July 2021

Interferon regulatory factor 8 regulates expression of acid ceramidase and infection susceptibility in cystic fibrosis.

J Biol Chem 2021 Jan-Jun;296:100650. Epub 2021 Apr 9.

Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address:

Most patients with cystic fibrosis (CF) suffer from acute and chronic pulmonary infections with bacterial pathogens, which often determine their life quality and expectancy. Previous studies have demonstrated a downregulation of the acid ceramidase in CF epithelial cells resulting in an increase of ceramide and a decrease of sphingosine. Sphingosine kills many bacterial pathogens, and the downregulation of sphingosine seems to determine the infection susceptibility of cystic fibrosis mice and patients. It is presently unknown how deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) connects to a marked downregulation of the acid ceramidase in human and murine CF epithelial cells. Here, we employed quantitative PCR, western blot analysis, and enzyme activity measurements to study the role of IRF8 for acid ceramidase regulation. We report that genetic deficiency or functional inhibition of CFTR/Cftr results in an upregulation of interferon regulatory factor 8 (IRF8) and a concomitant downregulation of acid ceramidase expression with CF and an increase of ceramide and a reduction of sphingosine levels in tracheal and bronchial epithelial cells from both human individuals or mice. CRISPR/Cas9- or siRNA-mediated downregulation of IRF8 prevented changes of acid ceramidase, ceramide, and sphingosine in CF epithelial cells and restored resistance to Pseudomonas aeruginosa infections, which is one of the most important and common pathogens in lung infection of patients with CF. These studies indicate that CFTR deficiency causes a downregulation of acid ceramidase via upregulation of IRF8, which is a central pathway to control infection susceptibility of CF cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113888PMC
August 2021

miR-122 promotes virus-induced lung disease by targeting SOCS1.

JCI Insight 2021 04 8;6(7). Epub 2021 Apr 8.

Priority Research Centre GrowUpWell, Experimental and Translational Respiratory Medicine Group, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.127933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119205PMC
April 2021
-->