Vaccination against Rabbit Hemorrhagic Disease Virus 2 (RHDV2) Using a Baculovirus Recombinant Vaccine Provides Durable Immunity in Rabbits.

Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

The Inverted Case Study Technique: Changing the Traditional Case-Study Approach to Prioritize Physiological Mechanisms Over Correct Diagnosis and Treatment.

The traditional case study has been used as a learning tool for the past 100 years and in our program, graduate physiology students are presented with a real-world scenario and must determine the diagnosis and treatment of the patient. We found that students defaulted to memorization of disease with treatment and bypassed gaining an understanding of the mechanistic physiology behind disease and treatment. To adjust our student's approach, we developed a novel way to enhance student learning. In order to accomplish this shift from memorization to physiological mastery, we created the Inverted Case Study. This approach diverges from the traditional model in that students are given the diagnosis and treatment beforehand and are tasked with explaining the actual physiology of the case. In this way, students can no longer rely on the memorization of symptoms-disease-treatment, but rather gain a solid understanding of the physiological mechanisms of the disease since that is the focus of ICST. The inverted case study approach is an effective approach to apply and hone critical thinking skills.

Microalgae cultivation using ammonia and carbon dioxide concentrations typical of pig barns.

While global population growth drives increased production efficiency in animal agriculture, there is a growing demand for environmentally friendly practices, particularly in reducing air pollutant emissions from concentrated animal feeding operations. This study explores the potential of cultivating microalgae in photobioreactors (PBRs) as an eco-friendly and cost-effective approach to mitigate NH3 and CO2 emissions from pig barns. Unlike traditional physicochemical mitigation systems, microalgae offer a renewable solution by converting pollutants into valuable biomass. The research focused on Scenedesmus dimorphus growth under typical NH3 and CO2 concentrations found in the indoor air of pig barns. Four NH3 (0, 12, 25, and 50 ppm) and four CO2 concentrations (350, 1200, 2350, and 3500 ppm) were tested using photobioreactors. Results showed a maximum specific growth rate of 0.83 d-1 with 12 ppm NH3 and 3500 ppm CO2. The dry biomass concentration was significantly higher (1.16 ± 0.08 g L-1; p < 0.01) at 25 ppm NH3 and 2350 ppm CO2 than other test conditions. S. dimorphus demonstrated the peak NH3 and CO2 fixation rates (23.8 ± 2.26 mg NH3 L-1 d-1 and 432.24 ± 41.09 mg CO2 L-1 d-1) at 25 ppm NH3 and 2350 ppm CO2. These findings support the feasibility of using algae to effectively remove air pollutants in pig barns, thereby improving indoor air quality.

Practitioner/Practice- and Patient-Based Factors Contributing to Dental Practitioner Treatment Recommendations for Patients with Pain-Related TMDs: Findings from the National Dental PBRN.

AIMS: To document National Dental Practice-Based Research Network (PBRN) practitioner treatment recommendations for patients with painful temporomandibular disorders (TMDs) and to identify practitioner/practice- and patient-related factors contributing to treatment recommendations made at the initial clinical visit. METHODS: This prospective single-sample cohort study formed groups based on treatment recommendations made by 185 dental practitioners who treated 1,901 patients with painful TMDs. At the baseline visit, which this article describes, practitioners provided patients with their diagnoses and a treatment plan and then completed a comprehensive questionnaire. RESULTS: Self-care, an intraoral appliance, medication, and practitioner-recommended jaw exercises were the most frequently recommended treatments. Practitioners recommended multiple treatments to most patients. TMD signs, symptoms, and diagnoses were primary considerations in treatment planning, but the practitioner's expectations for improvement were only significant for intraoral appliances and self-care. Female practitioners and those with expertise in TMDs more frequently recommended patient-directed and multidisciplinary treatments compared to their counterparts. CONCLUSIONS: Practitioners used a wide range of treatments for patients with few consistent patterns. The propensity to use TMD signs, symptoms, and diagnoses when making treatment recommendations suggests a tendency to conceptualize patients using the biomedical model. Infrequent referral to nondental providers suggests a lack of availability of these providers, a misunderstanding of the complexity of TMDs, and/or discomfort with assessment of psychosocial factors. Implications include the need for comprehensive training in the assessment and management of TMD patients during dental school and participation in TMD continuing education courses following evidence-based guidelines.

Granulocyte Colony-Stimulating Factor is a Determinant of Severe Bronchopulmonary Dysplasia and Coincident Retinopathy.

Bronchopulmonary dysplasia (BPD), also called chronic lung disease of immaturity, afflicts approximately one third of all extremely premature infants, causing lifelong lung damage. There is no effective treatment other than supportive care. Retinopathy of prematurity (ROP), which impairs vision irreversibly, is common in BPD, suggesting a related pathogenesis. However, specific mechanisms of BPD and ROP are not known. Herein, a neonatal mouse hyperoxic model of coincident BPD and retinopathy was used to screen for candidate mediators, which revealed that granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3, was up-regulated significantly in mouse lung lavage fluid and plasma at postnatal day 14 in response to hyperoxia. Preterm infants with more severe BPD had increased plasma G-CSF. G-CSF-deficient neonatal pups showed significantly reduced alveolar simplification, normalized alveolar and airway resistance, and normalized weight gain compared with wild-type pups after hyperoxic lung injury. This was associated with a marked reduction in the intensity, and activation state, of neutrophilic and monocytic inflammation and its attendant oxidative stress response, and protection of lung endothelial cells. G-CSF deficiency also provided partial protection against ROP. The findings in this study implicate G-CSF as a pathogenic mediator of BPD and ROP, and suggest the therapeutic utility of targeting G-CSF biology to treat these conditions.

Particle generation and dispersion from high-speed dental drilling.

OBJECTIVE: To investigate the characteristics of particle generation and dispersion during dental procedure using digital inline holography (DIH) METHODS: Particles at two locations, near-field and far-field, which represent the field closer to the procedure location and within 0.5 m from the procedure location respectively, are studied using two different DIH systems. The effect of three parameters namely rotational speed, coolant flow rate, and bur angle on particle generation and dispersion are evaluated by using 10 different operating conditions. The particle characteristics at different operating conditions are estimated from the holograms using machine learning-based analysis. RESULTS: The particle concentration decreased by at least two orders of magnitude between the near-field and far-field locations across the 10 different operating conditions, indicating significant dispersion of the particles. High rotational speed is found to produce a larger number of smaller particles, while lower rotational speeds generate larger particles. Coolant flow rate is found to have a greater impact on particle transport to the far-field location. Irregular shape dental particles account for 29% of total particles at far-field location, with the majority of these irregular shape particles having diameters ranging from 12 to 18 µm. CONCLUSIONS: All three parameters have significant effects on particle generation and dispersion, with rotational speed having a more significant influence on particle generation at near-field and coolant flow rate playing a more important role on particle transport to the far-field. CLINICAL RELEVANCE: This study provides valuable insights on particle characteristics during high-speed drilling. It can help dental professionals minimize exposure risks for themselves and patients by optimizing clinical operating conditions.

A Controlled Study of Biopsychosocial Differences Observed in Masticatory Myalgia With and Without Pain Referral.

AIMS: To assess differences in biopsychosocial factors between participants with masticatory myofascial pain with referral (MFPwR), with myalgia without referral (Mw/oR), and community controls without TMDs. METHODS: Study participants were diagnosed with MFPwR (n = 196), Mw/oR (n = 299), or as a non-TMD community control (n = 87) by two calibrated examiners at each of three study sites. Pain chronicity, pain on palpation of masticatory muscle sites, and pressure pain thresholds (PPT) at 12 masticatory muscle, 2 trigeminal, and 2 nontrigeminal control sites were recorded. Psychosocial factors assessed included anxiety, depression, and nonspecific physical symptoms (Symptom Checklist-90 Revised); stress (Perceived Stress Scale); and health-related quality of life (Short Form Health Survey). Comparisons among the three groups were adjusted for age, sex, race, education, and income using multivariable linear regression. The significance threshold was set at P = .017 (.05 / 3) for subsequent pairwise comparisons. RESULTS: Compared to the Mw/oR group, the MFPwR group had significantly greater pain chronicity, number of painful muscle sites, anxiety, depression, nonspecific physical symptoms, and impaired physical health (P < .017). The MFPwR group also had significantly lower PPTs for masticatory sites (P < .017). Both muscle pain groups differed significantly from the non-TMD community control group for all outcome measures (P < .017). CONCLUSION: These findings support the clinical utility of separating MFPwR from Mw/oR. Patients with MFPwR are more complex from a biopsychosocial perspective than Mw/oR patients, which likely affects prognosis and supports consideration of these factors in case management.

Enhanced Lyn Activity Causes Severe, Progressive Emphysema and Lung Cancer.

The epidemiological patterns of incident chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma are changing, with an increasing fraction of disease occurring in patients who are never-smokers or were not exposed to traditional risk factors. However, causative mechanism(s) are obscure. Overactivity of Src family kinases (SFKs) and myeloid cell-dependent inflammatory lung epithelial and endothelial damage are independent candidate mechanisms, but their pathogenic convergence has not been demonstrated. Here we present a novel preclinical model in which an activating mutation in Lyn, a nonreceptor SFK that is expressed in immune cells, epithelium, and endothelium-all strongly implicated in the pathogenesis of COPD-causes spontaneous inflammation, early-onset progressive emphysema, and lung adenocarcinoma. Surprisingly, even though activated macrophages, elastolytic enzymes, and proinflammatory cytokines were prominent, bone marrow chimeras formally demonstrated that myeloid cells were not disease initiators. Rather, lung disease arose from aberrant epithelial cell proliferation and differentiation, microvascular lesions within an activated endothelial microcirculation, and amplified EGFR (epidermal growth factor receptor) expression. In human bioinformatics analyses, LYN expression was increased in patients with COPD and was correlated with increased EGFR expression, a known lung oncogenic pathway, and LYN was linked to COPD. Our study shows that a singular molecular defect causes a spontaneous COPD-like immunopathology and lung adenocarcinoma. Furthermore, we identify Lyn and, by implication, its associated signaling pathways as new therapeutic targets for COPD and cancer. Moreover, our work may inform the development of molecular risk screening and intervention methods for disease susceptibility, progression, and prevention of these increasingly prevalent conditions.

Safety and Effectiveness of As-Needed Formoterol in Asthma Patients Taking Inhaled Corticosteroid (ICS)-Formoterol or ICS-Salmeterol Maintenance Therapy.

BACKGROUND: As-needed low-dose inhaled corticosteroid (ICS)-formoterol reliever is recommended in patients with asthma prescribed maintenance ICS-formoterol. Clinicians often ask whether ICS-formoterol reliever can be used with other maintenance ICS-long-acting ß2-agonists. OBJECTIVE: To evaluate the safety and effectiveness of as-needed formoterol in patients taking maintenance ICS-formoterol or ICS-salmeterol from the RELIEF study. METHODS: RELIEF (SD-037-0699) was a 6-month, open-label study that randomized 18,124 patients with asthma to as-needed formoterol 4.5 µg or salbutamol 200 µg on top of maintenance therapy. This post hoc analysis included patients on maintenance ICS-formoterol or ICS-salmeterol (n = 5436). The primary safety outcome was a composite of serious adverse events (SAEs) and/or adverse events leading to discontinuation (DAEs); the primary effectiveness outcome was time-to-first exacerbation. RESULTS: For both maintenance groups and both relievers, similar numbers of patients had ≥1 SAE and/or DAE. In patients taking maintenance ICS-salmeterol, but not ICS-formoterol, significantly more non-asthma-related and nonserious DAEs occurred with as-needed formoterol versus as-needed salbutamol (P = .0066 and P = .0034, respectively). In patients taking maintenance ICS-formoterol, there was a significantly lower risk in time-to-first exacerbation with as-needed formoterol versus as-needed salbutamol (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.70, 0.95; P = .007). In patients taking ICS-salmeterol maintenance, time-to-first exacerbation was not significantly different between treatment arms (HR: 0.95, 95% CI: 0.84, 1.06; P = .35). CONCLUSIONS: As-needed formoterol significantly reduced exacerbation risk compared with as-needed salbutamol when added to maintenance ICS-formoterol, but not to maintenance ICS-salmeterol. More DAEs were seen with ICS-salmeterol maintenance therapy plus as-needed formoterol. Further research is needed to assess whether this is relevant to as-needed combination ICS-formoterol.

Prime-boost, double-dose influenza vaccine immunity in COPD: a pilot observational study.

Background: COPD patients are more susceptible to viral respiratory infections and their sequelae, and have intrinsically weaker immune responses to vaccinations against influenza and other pathogens. Prime-boost, double-dose immunisation has been suggested as a general strategy to overcome weak humoral response to vaccines, such as seasonal influenza vaccination, in susceptible populations with weak immunity. However, this strategy, which may also provide fundamental insights into the nature of weakened immunity, has not been formally studied in COPD. Methods: We conducted an open-label study of seasonal influenza vaccination in 33 vaccine-experienced COPD patients recruited from established cohorts (mean age 70 (95% CI 66.9-73.2) years; mean forced expiratory volume in 1 s/forced vital capacity ratio 53.4% (95% CI 48.0-58.8%)). Patients received two sequential standard doses of the 2018 quadrivalent influenza vaccine (15 µg haemagglutinin per strain) in a prime-boost schedule 28 days apart. We measured strain-specific antibody titres, an accepted surrogate of likely efficacy, and induction of strain-specific B-cell responses following the prime and boost immunisations. Results: Whereas priming immunisation induced the expected increase in strain-specific antibody titres, a second booster dose was strikingly ineffective at further increasing antibody titres. Similarly, priming immunisation induced strain-specific B-cells, but a second booster dose did not further enhance the B-cell response. Poor antibody responses were associated with male gender and cumulative cigarette exposure. Conclusions: Prime-boost, double-dose immunisation does not further improve influenza vaccine immunogenicity in previously vaccinated COPD patients. These findings underscore the need to design more effective vaccine strategies for COPD patients for influenza.

Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma.

BACKGROUND: Type 2 endotype asthma is driven by IL-4 and IL-13 signaling via IL-4Ra, which is highly expressed on airway epithelium, airway smooth muscle, and immunocytes in the respiratory mucosa, suggesting potential advantages of an inhalable antagonist. Lipocalin 1 (Lcn1), a 16 kDa protein abundant in human periciliary fluid, has a robust drug-like structure well suited to protein engineering, but it has never been used to make an inhaled Anticalin protein therapeutic. OBJECTIVES: We sought to reengineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile. METHODS: Lcn1 was systematically modified by directed protein mutagenesis yielding a high-affinity, slowly dissociating, long-acting full antagonist of IL-4Ra designated PRS-060 with properties analogous to dupilumab, competitively antagonizing IL-4Ra-dependent cell proliferation, mucus induction, and eotaxin expression in vitro. Because PRS-060 displayed exquisite specificity for human IL-4Ra, with no cross-reactivity to rodents or higher primates, we created a new triple-humanized mouse model substituting human IL-4Ra, IL-4, and IL-13 at their correct syntenic murine loci to model clinical dosing. RESULTS: Inhaled PRS-060 strongly suppressed acute allergic inflammation indexes in triple-humanized mice with a duration of action longer than its bulk clearance, suggesting that it may act locally in the lung. CONCLUSION: Lcn1 can be reengineered into the Anticalin antagonist PRS-060 (elarekibep), exemplifying a new class of inhaled topical, long-acting therapeutic drugs with the potential to treat type 2 endotype asthma.

Cigarette smoke depletes alveolar macrophages and delays clearance of Legionella pneumophila.

Legionella pneumophila is the main etiological agent of Legionnaires' disease, a severe bacterial pneumonia. L. pneumophila is initially engulfed by alveolar macrophages (AMs) and subvert normal cellular functions to establish a replicative vacuole. Cigarette smokers are particularly susceptible to developing Legionnaires' disease and other pulmonary infections; however, little is known about the cellular mechanisms underlying this susceptibility. To investigate this, we used a mouse model of acute cigarette smoke exposure to examine the immune response to cigarette smoke and subsequent L. pneumophila infection. Contrary to previous reports, we show that cigarette smoke exposure alone causes a significant depletion of AMs using enzymatic digestion to extract cells, or via imaging intact lung lobes by light-sheet microscopy. Furthermore, treatment of mice deficient in specific types of cell death with smoke suggests that NLRP3-driven pyroptosis is a contributor to smoke-induced death of AMs. After infection, smoke-exposed mice displayed increased pulmonary L. pneumophila loads and developed more severe disease compared with air-exposed controls. We tested if depletion of AMs was related to this phenotype by directly depleting them with clodronate liposomes and found that this also resulted in increased L. pneumophila loads. In summary, our results showed that cigarette smoke depleted AMs from the lung and that this likely contributed to more severe Legionnaires' disease. Furthermore, the role of AMs in L. pneumophila infection is more nuanced than simply providing a replicative niche, and our studies suggest they play a major role in bacterial clearance.

Growth of Scenedesmus dimorphus in swine wastewater with versus without solid-liquid separation pretreatment.

Scenedesmus dimorphus was cultivated in raw and pretreated swine wastewater (SW) with 6-L photobioreactors (PBRs) to investigate the effect of solid-liquid separation on algal growth. The same aerated PBRs containing no algae were used as control. Moderate COD and nitrogen removal from the SW was achieved with the algal PBRs. However, compared to the control reactors, they offered no consistent treatment boost. Improved algal growth occurred in the pretreated SW, as measured by maximum algal cell count (3202 ± 275 × 106 versus 2286 ± 589 × 106 cells L-1) and cell size. The enhanced algal growth in the pretreated SW resulted in relatively high nitrogen (5.7 %) and organic matter contents in the solids harvested at the end of cultivation experiments, with ∼25.6 % of nitrogen in the SW retained in the solids and ∼9.1 % absorbed by algae. The pretreatment also resulted in elevated phosphorus removal. This study is anticipated to foster the development of microalgae-based SW treatment processes.

Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells.

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.

Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD.

OBJECTIVE: Novel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of 1305 proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology. METHODS: Serum samples were collected from 241 COPD subjects in the multicenter French Cohort of Bronchial obstruction and Asthma to measure the expression of 1305 proteins using SOMAscan proteomic platform. Clustering of the proteomics was applied to identify disease subtypes and their functional annotation and association with key clinical parameters were examined. Cluster findings were revalidated during a follow-up visit, and compared to those obtained in a group of 47 COPD patients included in the Melbourne Longitudinal COPD Cohort. RESULTS: Unsupervised clustering identified two clusters within COPD subjects at inclusion. Cluster 1 showed elevated levels of factors contributing to tissue injury, whereas Cluster 2 had higher expression of proteins associated with enhanced immunity and host defense, cell fate, remodeling and repair and altered metabolism/mitochondrial functions. Patients in Cluster 2 had a lower incidence of exacerbations, unscheduled medical visits and prevalence of emphysema and diabetes. These protein expression patterns were conserved during a follow-up second visit, and substanciated, by a large part, in a limited series of COPD patients. Further analyses identified a signature of 15 proteins that accurately differentiated the two COPD clusters at the 2 visits. CONCLUSIONS: This study provides insights into COPD heterogeneity and suggests that overexpression of factors involved in lung immunity/host defense, cell fate/repair/ remodelling and mitochondrial/metabolic activities contribute to better clinical outcomes. Hence, high throughput proteomic assay offers a powerful tool for identifying COPD endotypes and facilitating targeted therapies.

A novel vaccine candidate against rabbit hemorrhagic disease virus 2 (RHDV2) confers protection in domestic rabbits.

OBJECTIVE: To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits. ANIMALS: 40 New Zealand White rabbits obtained from a commercial breeder. PROCEDURES: Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2. Rabbits were challenged with oral suspensions containing infectious virus and monitored for clinical disease for up to 10 days. Rabbits that died or were euthanized following infection were necropsied, and livers were evaluated for viral RNA via RT-PCR. RESULTS: None of the vaccinated animals (0/9) exhibited clinical disease or mortality following infection with RHDV2 while 9/13 (69%) of the control animals succumbed to lethal disease following infection. CLINICAL RELEVANCE: The novel vaccine described herein provided complete protection against lethal infection following RHDV2 challenge. Outside of emergency use, there are currently no licensed vaccines against RHDV2 on the market in the United States; as such, this vaccine candidate would provide an option for control of this disease now that RHDV2 has become established in North America.

Cross-talk between IL-6 trans-signaling and AIM2 inflammasome/IL-1ß axes bridge innate immunity and epithelial apoptosis to promote emphysema.

Pulmonary emphysema is associated with dysregulated innate immune responses that promote chronic pulmonary inflammation and alveolar apoptosis, culminating in lung destruction. However, the molecular regulators of innate immunity that promote emphysema are ill-defined. Here, we investigated whether innate immune inflammasome complexes, comprising the adaptor ASC, Caspase-1 and specific pattern recognition receptors (PRRs), promote the pathogenesis of emphysema. In the lungs of emphysematous patients, as well as spontaneous gp130F/F and cigarette smoke (CS)-induced mouse models of emphysema, the expression (messenger RNA and protein) and activation of ASC, Caspase-1, and the inflammasome-associated PRR and DNA sensor AIM2 were up-regulated. AIM2 up-regulation in emphysema coincided with the biased production of the mature downstream inflammasome effector cytokine IL-1ß but not IL-18. These observations were supported by the genetic blockade of ASC, AIM2, and the IL-1 receptor and therapy with AIM2 antagonistic suppressor oligonucleotides, which ameliorated emphysema in gp130F/F mice by preventing elevated alveolar cell apoptosis. The functional requirement for AIM2 in driving apoptosis in the lung epithelium was independent of its expression in hematopoietic-derived immune cells and the recruitment of infiltrating immune cells in the lung. Genetic and inhibitor-based blockade of AIM2 also protected CS-exposed mice from pulmonary alveolar cell apoptosis. Intriguingly, IL-6 trans-signaling via the soluble IL-6 receptor, facilitated by elevated levels of IL-6, acted upstream of the AIM2 inflammasome to augment AIM2 expression in emphysema. Collectively, we reveal cross-talk between the AIM2 inflammasome/IL-1ß and IL-6 trans-signaling axes for potential exploitation as a therapeutic strategy for emphysema.

Cultivation of Scenedesmus dimorphus with air contaminants from a pig confinement building.

The continual consolidation and concentration of animal feeding operations (AFOs) raises various environmental challenges, including air pollutant emission. Cost-effective mitigation technologies are pursued to protect the health and wellbeing of animals and farmers as well as the environment. Previous lab studies utilized ammonia (NH3) and carbon dioxide (CO2), two major air pollutants in AFOs, for microalgal cultivation. However, the field performance of this algae-based mitigation approach has yet to be investigated. In this study, two photobioreactors (PBRs) were tested in a nursery pig barn to mitigate NH3 and CO2 while growing Scenedesmus dimorphus (S. dimorphus). Pit air was fed into the PBRs where the two pollutants were adsorbed by S. dimorphus as nutrients to produce algal biomass and oxygen gas (O2). The cleaned air then recirculated back to the room space. S. dimorphus reached its maximum cell count on the 17th day of the experiment when NH3 and CO2 concentrations in the pit air were 25.6 ppm and 3150 ppm, respectively. The maximum biomass concentration occurred on the 11th day when the NH3 and CO2 concentrations were 14.6 and 2250 ppm, respectively. The average mitigation efficiency was 31-50% for NH3 and 1-1.7% for CO2. The costs for removing 1 g NH3 and CO2 were estimated to be $3.77 and $0.20, respectively. This study shows that an integrated PBR system is technically feasible for reducing pig barn air pollutant emission while producing microalgae as a valuable product.

BigMouth: development and maintenance of a successful dental data repository.

Few clinical datasets exist in dentistry to conduct secondary research. Hence, a novel dental data repository called BigMouth was developed, which has grown to include 11 academic institutions contributing Electronic Health Record data on over 4.5 million patients. The primary purpose for BigMouth is to serve as a high-quality resource for rapidly conducting oral health-related research. BigMouth allows for assessing the oral health status of a diverse US patient population; provides rationale and evidence for new oral health care delivery modes; and embraces the specific oral health research education mission. A data governance framework that encouraged data sharing while controlling contributed data was initially developed. This transformed over time into a mature framework, including a fee schedule for data requests and allowing access to researchers from noncontributing institutions. Adoption of BigMouth helps to foster new collaborations between clinical, epidemiological, statistical, and informatics experts and provides an additional venue for professional development.

Vaccine strain affects seroconversion after influenza vaccination in COPD patients and healthy older people.

Though clinical guidelines recommend influenza vaccination for chronic obstructive pulmonary disease (COPD) patients and other high-risk populations, it is unclear whether current vaccination strategies induce optimal antibody responses. This study aimed to identify key variables associated with strain-specific antibody responses in COPD patients and healthy older people. 76 COPD and 72 healthy participants were recruited from two Australian centres and inoculated with influenza vaccine. Serum strain-specific antibody titres were measured pre- and post-inoculation. Seroconversion rate was the primary endpoint. Antibody responses varied between vaccine strains. The highest rates of seroconversion were seen with novel strains (36-55%), with lesser responses to strains included in the vaccine in more than one consecutive year (27-33%). Vaccine responses were similar in COPD patients and healthy participants. Vaccine strain, hypertension and latitude were independent predictors of seroconversion. Our findings reassure that influenza vaccination is equally immunogenic in COPD patients and healthy older people; however, there is room for improvement. There may be a need to personalise the yearly influenza vaccine, including consideration of pre-existing antibody titres, in order to target gaps in individual antibody repertoires and improve protection.