Fertility desires and sexual behaviours among women recovering from genital fistula repair in Eldoret, Kenya.

OBJECTIVES: The reproductive desire of women following genital fistula repair surgery is complex, varied and often not addressed, although it carries significant consequences. The aim of this study was to better understand the fertility desires and sexual behaviours of women who recently underwent surgical repair of a genital fistula. METHODS: This is a secondary analysis of a retrospective cohort study designed to assess the effectiveness of Beyond Fistula, a reintegration programme for women recovering from genital fistula surgery in Eldoret, Kenya. One hundred women who participated in the Beyond Fistula programme between 2013 and 2019 were interviewed in person regarding future fertility desire, current sexual behaviour and contraceptive use. RESULTS: Among the 79 reproductive-aged women included in this study, 63.3% reported no future desire for pregnancy. Those that desired another pregnancy were significantly younger (48.3% were 18-29 years old vs. 66.0% were 35 years old or more, p = 0.004), had fewer living children (70% had 0-2 children vs. 56% had 3 or more children, p < 0.001), and a lower level of food insecurity (27.6% reported no to marginal insecurity vs. 14%, p = 0.014). Current sexual activity was marginally different between women who did and did not desire future pregnancy (82.8% vs. 66.0%, p = 0.053). Of the 50 women in our study who did not desire pregnancy, 62.0% were sexually active and of these, only 38.7% were preventing pregnancy. Lack of knowledge and access to methods were most commonly cited as barriers to use. CONCLUSIONS: Many women recovering from genital fistula surgery do not desire pregnancy and are sexually active but are not using a method to prevent pregnancy. The potential for post-surgical reintegration programmes to address education and access to contraception is a vital and unmet need to promote reproductive empowerment in this population of women as they reestablish their lives.

Improving Stroke Measure Compliance and Outcomes Through Hospital Collaboration.

Globally, national stroke registries have been shown to improve the quality of patient care and outcomes. However, registry utilization and implementation vary by country. In the United States, stroke-specific performance measures must be met to achieve and maintain stroke center certification awarded by the state or nationally accredited certifying bodies. The 2 stroke registries available in the United States are the American Heart Association Get With The Guidelines-Stroke registry, which is voluntary, and the Paul Coverdell National Acute Stroke Registry, funded competitively to states by the Centers for Disease Control and Prevention. Compliance with stroke processes of care is variable, and quality improvement initiatives among organizations have been shown to have an impact on improving stroke care delivery. However, the effectiveness of interorganizational continuous quality improvement approaches, especially among competing institutions, to improving stroke care is ambiguous, and no uniform governance for successful interhospital collaboration has been identified. The purpose of this article is to review national initiatives focused on interorganizational collaboration to improve stroke care delivery with a focus on interhospital collaboration in the United States to improve stroke performance measures specific to stroke center certification. The state of Kentucky's experience and utilization of the Institute for Healthcare Improvement Breakthrough Series model with key strategies for success will be discussed to serve as a foundation and empower novice stroke leaders in learning health systems. The models may be adapted internationally for application to stroke-specific care process improvement locally, regionally, and nationally; among organizations within the same health system or competing systems; and among organizations with funding or without funding to improve stroke performance measures.

Urinary glucocorticoids in harbour seal (Phoca vitulina) pups during rehabilitation.

The glucocorticoid (GC) hormone cortisol is often measured in seals to indicate their stress levels, although other endogenous GCs are usually overlooked. We investigated concentrations of four endogenous GCs in the urine of "orphan" harbour seal pups in rehabilitation. We hypothesised that the GC levels would be elevated if pups were socially isolated, without water access, and with low body mass. Ninety-six samples were collected from 32 pups at four different rehabilitation centres and were analysed by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry. Median urinary creatinine (Cr) concentrations of endogenous prednisolone (31.6 ng/mg/Cr) and prednisone (31.1 ng/mg/Cr) occurred in similar magnitude to cortisol (37.0 ng/mg/Cr), while median cortisone concentrations were higher (390 ng/mg/Cr). Prednisolone and prednisone concentrations were more strongly inversely related to pup growth rate and pup mass than cortisol and cortisone. Concentrations of all four GCs decreased with mass gain for pups with water access but did not decrease for pups without water; linear mixed models indicated the interaction between these trends was significant for cortisol and cortisone, but not for prednisolone or prednisone. These results indicate the potential value of measuring all four of these endogenous GC hormones in phocid seal pups.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Exploring the gap between refugee-background communities' needs and existing community-based physical activity programs in Australia.

Physical activity programs run by local government, public health and not-for-profit sectors are a key public health strategy for improving rates of physical activity within local communities. However, these programs are underutilized. This is especially the case among members of refugee-background communities whose participation could have far-ranging and multilevel benefits. To explore how greater engagement among refugee-background communities with these programs could be fostered in Brisbane, Queensland, Australia, a qualitative study was undertaken from the perspectives of both community-based physical activity program providers and agencies involved in delivering services to refugee-background communities. This study involved a series of semi-structured interviews with a purposive sample of personnel from agencies that work with individuals and families from refugee-background communities and organizations that provide low-cost or no-cost physical activity programs and initiatives. Reflexive thematic analysis was used to interpret meaning from these data. Three themes relating to how participation in community-based physical activity programs could be improved among refugee-background communities were identified: improving cultural safety through intersectoral collaboration; confronting constraints imposed by the broader public health policy environment; and building capacity and empowering the community to diversify the sector. The findings highlight the importance of localized, deep-level intersectoral collaborations in bridging the gap between the health and social care needs of refugee-background communities and existing physical activity programs. However, a range of systems-produced barriers to the creation of such collaborations must be addressed to enable local actors to help mitigate and address the systemic exclusion of marginalized populations from participation in broader society.

This qualitative study explored how participation in community-based physical activity programs could be improved among refugee-background communities. To do this, community-based physical activity program providers and agencies involved in delivering services to refugee-background communities in Brisbane, Queensland, Australia, were invited to participate in a semi-structured interview. Reflexive thematic analysis was then used to identify patterns and themes within the interview data. This analysis found that the cultural safety of community-based physical activity programs needs to be improved. From participants' perspectives, a good way to do this is through genuine collaboration between services providing community-based physical activity programs and those working directly with refugee-background communities. Relatedly, however, participants experienced the broader public health policy environment as increasingly bureaucratic and market orientated, where top-down models are adopted and funding is ad hoc and insecure. This environment was identified as constraining the ability of service providers and agencies to collaborate on the level required to improve cultural safety for members of refugee-background communities. Relatedly, the analysis also identified the importance of building the capacity and empowering members of refugee-background communities for diversifying the sector and increasing the participation rates of refugee-background communities in community-based physical activity programs.

Trail running events contribute microplastic pollution to conservation and wilderness areas.

Clothing and footwear designed for trail running shed microplastics (MPs) during use. Trail running events may therefore present a significant source of MP pollution in conservation and wilderness areas. Microplastics may present long-term risks to biodiversity and endemic plant and animal species in such areas. In this study, we used a before-after-control-impact approach to quantify and characterise MP emissions from clothing and shoe outsoles during trail running events. Microplastic deposition on trail surfaces was assessed using both a controlled study and during two public trail running events in New South Wales, Australia (the Duval Dam Buster and the Washpool World Heritage Trail Race). Microplastics were present on trails after all events and included fibres and rubber fragments. Microplastic counts varied considerably depending on trail surface hardness and gradient, and clothing and footwear properties. The controlled study showed running tights (leggings) and shoes with soft rubber outsoles produced more MPs than shirts and hard rubbers. In the trail running events, abrasive wear to shoe outsoles produced an average of 0.3 ± 0.1 to 0.9 ± 0.2 MPs/linear metre/runner, and clothing produced 0.7 ± 0.3 to 2.0 ± 0.3 fibres/linear metre/runner, with fibres accounting for 63-69% of MPs. Microplastic deposition from both footwear and clothing was higher on sloped and rock trail surfaces than flat and soil surfaces. Laser Direct Infrared (LDIR) Imaging indicated the main types of MPs present on trails were polyurethane, polyethylene terephthalate and polyamide. Trail running is increasing in popularity and large-scale events may cause a rapid and significant input of MPs in protected areas. Land managers, event coordinators and outdoor apparel manufacturers could mitigate MP impacts however, by diverting foot traffic around ecologically sensitive areas, capping participant numbers, and developing abrasion resistant clothing and footwear.

SARS-CoV-2 infection and seizures: the perfect storm.

Seizures have been increasingly identified as a neurologic manifestation of coronavirus disease 2019 (COVID-19) infection. They may be symptomatic due to systemic infections, as a result of direct central nervous system (CNS) invasion, or occur in response to inflammatory reactions to the virus. It is possible that proinflammatory molecules released in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to hyperexcitability and epileptogenesis, similar to infections caused by other neurotrophic viruses. Cerebral spinal fluid (CSF) in patients with COVID-19 and seizures is negative for SARS-CoV-2 (PCR) in the majority of patients, but has been found to be positive for proinflammatory molecules like IL-6, IL-8, and anti-neuronal autoantibodies. Electroencephalogram (EEG) in COVID-19 patients are nonspecific. However, in the encephalopathic and critically ill subpopulation, EEG is essential in detecting nonconvulsive seizures and status epilepticus which is associated with increased overall mortality in COVID-19 patients. Thus, as encephalopathy is often the only CNS symptom evidenced in patients with nonconvulsive seizures, more judicious use of continuous EEG in encephalopathic COVID-19 patients should be considered. This would facilitate earlier detection and treatment of seizures in this population, which would ultimately improve outcomes. Further research into the onset and potential for development of seizures and epilepsy in patients with COVID-19 is needed.

Care of the Patient With Acute Ischemic Stroke (Prehospital and Acute Phase of Care): Update to the 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association.

The year 2020 was the year of the nurse, celebrating nurse scholarship, innovation, and leadership by promoting scientific nursing research, improving nursing practice, advancing nursing education, and providing leadership to influence health policy. As architects of stroke care, neuroscience nurses play a vital role in collaborating and coordinating care between multiple health professionals. Nurses improve accessibility and equity through telestroke, emergency medical services, and mobile stroke units and are integral to implementing education strategies by advocating and ensuring that patients and caregivers receive stroke education while safely transitioning through the health care system and to home. Stroke care is increasingly complex in the new reperfusion era, requiring nurses to participate in continuing education while attaining levels of competency in both the acute and recovery care process. Advanced practice nurses are taking the lead in many organizations, serving as prehospital providers on mobile stroke units, participating as members of the stroke response team, and directing stroke care protocols in the emergency department. This scientific statement is an update to the 2009 "Comprehensive Overview of Nursing and Interdisciplinary Care of the Acute Ischemic Stroke Patient." The aim is to provide a comprehensive review of the scientific evidence on nursing care in the prehospital and hyperacute emergency hospital setting, arming nurses with the necessary tools to provide evidenced-based high-quality care.

Airway Elastin is increased in severe asthma and relates to proximal wall area: histological and computed tomography findings from the U-BIOPRED severe asthma study.

BACKGROUND: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. OBJECTIVE: Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. METHODS: Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. RESULTS: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18-20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. CONCLUSION: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

Ventilatory support at home for children: A joint position paper from the Thoracic Society of Australia and New Zealand/Australasian Sleep Association.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

Women's experiences of safety apps for sexualized violence: a narrative scoping review.

BACKGROUND: Sexualized violence against women is a significant human rights problem worldwide. Safety apps have the capacity to provide women with resources to prevent or respond to experiences of sexualized violence. METHODS: The aim of the following study was to review the scope of the literature on women's experiences of safety apps related to sexualized violence. The databases Embase, MEDLINE, PsycINFO, and Scopus were systematically searched, and seven studies were included in this review. RESULTS: Thematic analysis identified the following themes in the literature: (1) security; (2) accessibility; and (3) knowledge. CONCLUSION: The gaps in the literature are identified and implications and recommendations for future research is discussed.

Sensitivity of Freshwater Australian Bass (Macquaria novemaculeata) and Silver Perch (Bidyanus bidyanus) to Waterborne Antimony: Exposure-Dose-Response Characteristics and Ion Homeostasis.

We conducted acute toxicity studies using semi-static protocols to examine the lethal responses of Australian bass and silver perch exposed to antimony (Sb) oxidation states in Sb(III) (10.5-30.5 mg L-1) and Sb(V) (95.9-258.7 mg L-1). Bioavailability and the effects of Sb on body ion regulation (Na, Ca, Mg, and K) were also investigated. Antimony species-specific effects were observed with exposure to both Sb oxidation states. Median lethal concentrations (LC50s) for Sb(III) were 13.6 and 18 mg L-1 for Australian bass and silver perch, respectively, and the LC50 for Sb(V) in Australian bass was 165.3 mg L-1. The LC50 could not be calculated for silver perch exposed to Sb(V) as the maximum exposure concentrations produced 40% mortality but a larger-than value of > 258.7 mg L-1 was estimated. Relative median potency values derived from the LC50s were 0.1 Sb(III) and 12.2 and 16.6 Sb(V) for Australian bass and silver perch, respectively, demonstrating greater toxicity of Sb(III) to both fish species. Antimony uptake in fish was observed. Median critical body residue (CBR50) values of 77.7 and 26.6 mg kg-1 for Sb(III) were estimated for Australian bass and silver perch, respectively, and 628.1 mg kg-1 for Sb(V) in Australian bass. Bioconcentration factors (BCFs) for both Sb(III) and Sb(V) did not change with exposure but the greater BCFs for fish exposed to Sb(III) indicate that it is more bioavailable than Sb(V) in acute exposure. No effects on whole-body Na, Ca, Mg, or K ions were observed with fish exposure to either Sb species.

A high yielding IFNAR1 ECD mammalian expression process for use in autoimmune disease drug development.

Interferon-alpha receptor 1 (IFNAR1) is a target of interest for recombinant biotherapeutics that block the JAK/STAT pathway. This pathway is believed to play a role in many diseases including Hepatitis B and C, Herpes Simplex, Multiple Sclerosis, and other autoimmune disorders. By using IFNAR1 as a target to block Type I IFN from binding to the JAK/STAT pathway and prevent activation of this target, autoimmune disease progression can be modulated. Current IFNAR1 extracellular domain (ECD) expression and purification protocols are labor intensive with low product yield and limited scalability. In this work, we evaluate three different expression systems (baculovirus, human embryonic kidney 293 (HEK293×), and Chinese hamster ovary (CHO)) to improve expression of IFNAR1 ECD. We demonstrate the benefits of utilizing mammalian CHO cell transient transfection to increase expression titer, as well as an improved two-step purification process performed using immobilized metal affinity chromatography (IMAC) as the capture step and Ceramic Hydroxyapatite (CHT) Type II for HMW impurity removal in flow through mode. This process showed an 20-fold increase in productivity compared to the baseline process as measured by grams purified per liter of cell culture fluid. Lastly, the improved process showed good scalability, enabling efficient purification of 3.6 g of product from a 30 L scale bioreactor.

CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells.

IL-17-high asthma with features of a psoriasis immunophenotype.

BACKGROUND: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. OBJECTIVE: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. METHODS: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17-high and IL-13-high asthma phenotypes. RESULTS: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17-high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and ß-defensin. CONCLUSION: The IL-17-high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.

BACKGROUND: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. OBJECTIVE: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. METHODS: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. RESULTS: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1ß, IL-8, and IL-1ß. CONCLUSIONS: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.

Stratification of asthma phenotypes by airway proteomic signatures.

BACKGROUND: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. OBJECTIVE: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. METHODS: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. RESULTS: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. CONCLUSION: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.

Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET.

BACKGROUND: Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma. METHODS: We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate-to-severe asthma of the U-BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry. RESULTS: Using stringent false discovery rate analysis, MMP-10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal eosinophil (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP-10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less-stringent conditions (raw P-value < 0.05, log2 fold change > 0.5), we defined a 73-gene set characteristic of the HE compared to the LE group. Thirty-three of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC-chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS-1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression. CONCLUSION: Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP-10 likely play an important role in these processes.

A new, practicable and economical cage design for experimental studies on small honey bee colonies.

Bees are in decline globally as a result of multiple stressors including pests, pathogens and contaminants. The management of bees in enclosures can identify causes of decline under standardized conditions but the logistics of conducting effect studies in typical systems used across several colonies is complex and costly. This study details a practicable, new and economical cage system that effectively houses live honey bee colonies to investigate the impact of physical conditions, biological factors and environmental contaminants on honey bee health. The method has broad application for a range of effect studies concerning honey bee development, physiology, survival and population dynamics because it enables entire colonies, as opposed to individual workers, to be managed well in captivity.

A Disintegrin and A Metalloproteinase-9 (ADAM9): A Novel Proteinase Culprit with Multifarious Contributions to COPD.

INTRODUCTION: Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice. METHODS: ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wild-type (WT) mice. WT and Adam9-/- mice were exposed to air or CS for 1-6 months, and COPD-like lung pathologies were measured. RESULTS: ADAM9 staining was increased in lung epithelial cells and macrophages in smokers and even more so in COPD patients and correlated directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 % predicted. Bronchial epithelial cell ADAM9 mRNA levels were higher in COPD patients than controls and correlated directly with pack-year smoking history. Plasma, BALF and sputum ADAM9 levels were similar in COPD patients and controls. CS exposure increased Adam9 levels in WT murine lungs. Adam9-/- mice were protected from emphysema development, small airway fibrosis, and airway mucus metaplasia. CS-exposed Adam9-/- mice had reduced lung macrophage counts, alveolar septal cell apoptosis, lung elastin degradation, and shedding of VEGFR2 and EGFR in BALF samples. Recombinant ADAM9 sheds EGF and VEGF receptors from epithelial cells to reduce activation of the Akt pro-survival pathway and increase cellular apoptosis. CONCLUSIONS: ADAM9 levels are increased in COPD lungs and linked to key clinical variables. Adam9 promotes emphysema development, and large and small airway disease in mice. Inhibition of ADAM9 could be a therapeutic approach for multiple COPD phenotypes.