Role of mechanical stress in regulating airway surface hydration and mucus clearance rates

Effective clearance of mucus is a critical innate airway defense mechanism, and under appropriate conditions, can be stimulated to enhance clearance of inhaled pathogens. It has become increasingly clear that extracellular nucleotides (ATP and UTP) and nucleosides (adenosine) are important regulators of mucus clearance in the airways as a result of their ability to stimulate fluid secretion, mucus hydration, and cilia beat frequency (CBF). One ubiquitous mechanism to stimulate ATP release is through external mechanical stress. This article addresses the role of physiologically-relevant mechanical forces in the lung and their effects on regulating mucociliary clearance (MCC). The effects of mechanical forces on the stimulating ATP release, fluid secretion, CBF, and MCC are discussed. Also discussed is evidence suggesting that airway hydration and stimulation of MCC by stress-mediated ATP release may play a role in several therapeutic strategies directed at improving mucus clearance in patients with obstructive lung diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)

Impacts of Federal Farm Program Payments on Cropland Values and Rental Rates: Evidence from County-level Data in South Dakota

Farmland values, cash rental rates, and federal farm program payments steadily increased in the Northern Plains from 1991 - 2001. Econometric models are used to examine the impacts of Federal farm payments on cropland values and rental rates, statewide and regional, in South Dakota during this time period

Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia: Role of cyclic stress in airway mucociliary transport

In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2-purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS-induced increase in ASL ATP concentration was sufficient to induce purinoceptor-mediated increases in ASL height and MCC, via inhibition of epithelial Na+-channel-mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+-activated chloride channels. In contrast, static, non-oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence

Teaching Foundational Aquatic Skills to Children in Open Water Environments

Learning to swim in a swimming pool might not prepare water competence sufficiently for different aquatic environments. The aim of this study was to assess the effectiveness of teaching children water safety knowledge and skills in open water environments (i.e., harbor, river, and surf). The aquatic knowledge and skills of 98 children (7-11 years old) were tested in a swimming pool before, immediately after, and three months after receiving a three-day intensive education program. At pre-test, typically fewer than 50% of children achieved a high level of water safety competence. After the program, competency in each of the six tasks assessed had increased with up to 80% of participants completing the tasks unassisted. Three-month retention of these skills was generally high (i.e., competency levels were either maintained or improved). A key challenge for future research will be to untangle the influences of maturation, order effects, and the open water education

Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype

Abnormalities in mucus production and qualitative properties such as mucus hydration are central to the pathophysiology of airway disease including cystic fibrosis, asthma, and chronic bronchitis. In vitro air–liquid interface epithelial cell cultures demonstrate direct relationships between mucociliary transport, periciliary liquid (PCL) height, and mucus concentration (expressed as percent solids or partial osmotic pressure). In health, the osmotic modulus/pressure of the PCL exceeds that of the mucus layer, resulting in efficient, low-friction movement of mucus. In disease, through multiple mechanisms, the osmotic pressure of the mucus begins to exceed basal PCL values, resulting in compression of the cilia and slowing of mucus transport. The in vivo data in both cystic fibrosis and chronic bronchitis parallel in vitro data demonstrating that when mucus osmotic pressure is increased, mucociliary clearance is decreased. In chronic bronchitis, there is a direct correlation between FEV1 and percent solids of mucus, demonstrating a strong relationship between disease progression and mucus abnormalities. Animal models, based mechanistically on raised sodium absorption (and therefore water absorption) from airway surfaces, mimic the pathophysiology of chronic obstructive pulmonary disease. Collectively, these data suggest the importance of mucus concentration in the pathogenesis of airway disease. It is important to understand the precise mechanisms that result in mucus hyperconcentration, for example, mucin overproduction versus abnormal regulation of ion/water transport, which may be unique to and characteristic of each disease phenotype. The measurement of mucus concentration may be a simple method to diagnose chronic bronchitis, monitor its progression, and serve as a biomarker for development of new therapies

Comment les premières expériences cliniques dans les communautés rurales influencent l'apprentissage des étudiants en matière de généralisme rural sous l’angle de la théorie de l'éducation

Introduction: Rural communities have poorer health compared to urban populations due partly to having lesser healthcare access. Rural placements during medical education can equip students with the knowledge and skills to work in rural communities, and, it is hoped, increase the supply of rural physicians. It is unclear how students gain knowledge of rural generalism during placements, and how this can be understood in terms of place-based and/or sociocultural educational theories. To gain insight into these questions we considered the experiences of pre-clerkship medical students who completed two mandatory four-week rural placements during their second year of medical school. Methods: Data was collected using semi-structured interviews or focus groups, followed by thematic analysis of the interview transcripts. Results: Rural placements allowed students to learn about rural generalism such as breadth of practice, and boundary issues. This occurred mainly by students interacting with rural physician faculty, with the effectiveness of precepting being key to students acquiring knowledge and skills and reporting a positive regard for the placement experience. Discussion: Our data show the central role of generalist physician preceptors in how and what students learn while participating in rural placements. Sociocultural learning theory best explains student learning, while place-based education theory helps inform the curriculum. Effective training and preparation of preceptors is likely key to positive student placement experiences.Introduction : Les communautés rurales sont en moins bonne santé que les populations urbaines, en partie parce qu'elles ont moins accès aux soins de santé. Les stages de médecine en milieu rural peuvent permettre aux étudiants d'acquérir les connaissances et les compétences nécessaires pour travailler dans les communautés rurales et, on l'espère, augmenter le nombre de médecins y travaillent. On ne sait pas clairement comment les étudiants acquièrent des connaissances sur le généralisme rural au cours de leurs stages, et comment cela peut être compris en termes de théories éducatives socioculturelles et/ou basées sur le lieu de travail.  Pour répondre à ces questions, nous avons étudié les expériences d'étudiants en médecine au pré-clinique qui ont effectué deux stages obligatoires de quatre semaines en milieu rural au cours de leur deuxième année d'études de médecine. Méthodes : Les données ont été recueillies au moyen d'entrevues semi-structurées ou de groupes de discussion, suivis d'une analyse thématique des transcriptions des entrevues. Résultats : Les stages en milieu rural ont permis aux étudiants de se familiariser avec le généralisme rural, notamment l'étendue de la pratique et les questions de limites. L'efficacité du préceptorat est essentielle pour que les étudiants acquièrent des connaissances et des compétences et qu'ils aient une expérience de stage positive. Discussion :  Nos données témoignent du rôle central que jouent les médecins généralistes précepteurs quant au contenu et modes d’apprentissage des étudiants lorsqu'ils participent à des stages en milieu rural. La théorie de l'apprentissage socioculturel est celle qui explique le mieux l'apprentissage des étudiants, tandis que la théorie de la formation fondée sur le lieu contribue à orienter le programme d'études. Une formation et préparation efficace des précepteurs est probablement la clé d'une expérience de stage positive pour les étudiants

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Developing a first principles approach to educating water skills for life to children

In New Zealand, despite the fact that the majority of drownings occur in open water, most swimming teaching occurs in public swimming pools. It is possible that learning to swim in a public swimming pool does not sufficiently prepare people to develop water competence when exposed to open water environments. This aim of this study was to address whether it is effective to teach children water safety knowledge and skills in open water environments. Based on existing research the following predictions were tested: 1) The water safety skill competency of NZ primary school children will be varied but overall quite low 2) The water safety skill competency of children will improve following a one week intervention program taught in open water environments 3) Following an intervention program taught in open water environments, the improvement in water safety skill competency of children will be retained for at least three months Ninety-eight primary school-aged children (7-11 years old) volunteered to participate and provided informed consent. Their water safety knowledge and skills were tested in a swimming pool before, immediately after, and three months after receiving a three-day education program delivered in open water environments (harbour, surf, river). The education program was conducted by teams of ‘expert providers’ with comprehensive experience and appropriate education qualifications. For each of the three test phases, participants were asked to attempt six tasks (i.e., Quiz, Buoyancy, Submersion, Obstacle Course, Simulated Rescue and Propulsion). The participant’s relative competency to perform the tasks unaided was assessed by observers on a 4-point scale. At pre-test, the percentage of children achieving a high level of competence on the six water safety tasks was typically less than 50%. In support of previous research, the water safety competencies of children were spread across a wide continuum of skilled behaviour and was quite low relative to those recommended in the Water Skills for Life program. It is concerning that approximately 60% of participants failed to complete a 5 minute continuous swim or an unsupported floating exercise without receiving additional help. Encouragingly there was strong support for the efficacy of the open water education program. Children improved their competency in each of the six tasks assessed. Furthermore, children demonstrated a good level of retention of these skills when assessed three months after the program had concluded. Caregivers offered very positive support for the education program and most felt that their child/children were definitely more aware of the dangers associated with open water environments and how to behave safely. Previous work had shown that 10 weeks of one hour lessons taught in swimming pools was effective in improving water safety knowledge and competency (Button et al., 2017). The current study indicates that similar levels of improvement can be obtained from an education program conducted within three days. A key challenge for future research will be to determine the transferability of water safety skills learnt in open water environments. It is recommended that New Zealand’s water safety sector work collaboratively to inform policy and strategies by: • Exploring and promoting opportunities to teach water safety knowledge and skills to New Zealanders in open water environments • Identifying and supporting ‘expert’ organisations best placed to provide education in different open water environments • Liaising with and lobbying the Ministry of Education and NZ schools to consider how best to integrate open water safety education with swimming pool based skill acquisition program

Obesity is associated with increased risk of invasive penile cancer

BACKGROUND: To validate the association between obesity and penile cancer at a population level, we conducted a matched case–control study linking the Iowa Department of Motor Vehicles Drivers’ License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI). METHODS: All men diagnosed with invasive penile squamous cell carcinoma from 1985 to 2010 were identified by SHRI. Two hundred sixty-six cancer cases and 816 cancer-free male controls, selected from the Iowa DLD, were matched within 5-year age and calendar year strata. Body mass index (BMI) was calculated using self-reported height and weight from the DLD. RESULTS: Conditional logistic regression was used to evaluate the association between BMI and the risk of developing invasive penile cancer. Obesity was significantly associated with an increased risk of developing penile cancer. For every five-unit increase in BMI the risk of invasive penile cancer increased by 53 % (OR 1.53, 95 % CI 1.29-1.81, p < 0.0001). CONCLUSION: We previously reported an association between obesity and higher risk of invasive penile cancer and advanced cancer stage at diagnosis in a hospital-based retrospective study. This population-based study confirms an association between obesity and invasive penile cancer

Monitoring airway mucus flow and ciliary activity with optical coherence tomography

Muco-ciliary transport in the human airway is a crucial defense mechanism for removing inhaled pathogens. Optical coherence tomography (OCT) is well-suited to monitor functional dynamics of cilia and mucus on the airway epithelium. Here we demonstrate several OCT-based methods upon an actively transporting in vitro bronchial epithelial model and ex vivo mouse trachea. We show quantitative flow imaging of optically turbid mucus, semi-quantitative analysis of the ciliary beat frequency, and functional imaging of the periciliary layer. These may translate to clinical methods for endoscopic monitoring of muco-ciliary transport in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD)