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Dental procedures often produce aerosols and spatter, which have the potential to transmit pathogens such as severe acute respiratory syndrome coronavirus 2. The existing literature is limited.Aerosols and spatter were generated from an ultrasonic scaling procedure on a dental manikin and characterized via 2 optical imaging methods: digital inline holography and laser sheet imaging. Capture efficiencies of various aerosol mitigation devices were evaluated and compared.The ultrasonic scaling procedure generated a wide size range of aerosols (up to a few hundred μm) and occasional large spatter, which emit at low velocity (mostly3 m/s). Use of a saliva ejector and high-volume evacuator (HVE) resulted in overall reductions of 63% and 88%, respectively, whereas an extraoral local extractor (ELE) resulted in a reduction of 96% at the nominal design flow setting.The study results showed that the use of ELE or HVE significantly reduced aerosol and spatter emission. The use of HVE generally requires an additional person to assist a dental hygienist, whereas an ELE can be operated hands free when a dental hygienist is performing ultrasonic scaling and other operations.An ELE aids in the reduction of aerosols and spatters during ultrasonic scaling procedures, potentially reducing transmission of oral or respiratory pathogens like severe acute respiratory syndrome coronavirus 2. Position and airflow of the device are important to effective aerosol mitigation.

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.

T2 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 16kD protein abundant in human periciliary fluid, has a robust drug-like structure well-suited to protein engineering, but has never been used to make an inhaled "Anticalin" protein therapeutic.To re-engineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile.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. As 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 hIL-4Ra, hIL-4, and hIL-13 at their correct syntenic murine loci to model clinical dosing.Inhaled PRS-060 strongly suppressed acute allergic inflammation indices in triple humanized mice with a duration of action longer than its bulk clearance suggesting it may act locally in the lung.Lcn1 can be re-engineered into the Anticalin antagonist PRS-060, exemplifying a new class of inhaled topical, long-acting therapeutic with potential to treat T2 endotype asthma.

It has been reported that a GM-CSF→CCL17 pathway, originally identified in vitro in macrophage lineage populations, is implicated in the control of inflammatory pain, as well as arthritic pain and disease. We explore, in this study and in various inflammation models, the cellular CCL17 expression and its GM-CSF dependence as well as the function of CCL17 in inflammation and pain. This study used models allowing the convenient cell isolation from Ccl17E/+ reporter mice; it also exploited both CCL17-dependent and unique CCL17-driven inflammatory pain and arthritis models, the latter permitting a radiation chimera approach to help identify the CCL17 responding cell type(s) and the mediators downstream of CCL17 in the control of inflammation and pain. We present evidence that 1) in the particular inflammation models studied, CCL17 expression is predominantly in macrophage lineage populations and is GM-CSF dependent, 2) for its action in arthritic pain and disease development, CCL17 acts on CCR4+ non–bone marrow–derived cells, and 3) for inflammatory pain development in which a GM-CSF→CCL17 pathway appears critical, nerve growth factor, CGRP, and substance P all appear to be required.

Aims: Excessive reactive oxygen species (ROS) are detrimental to immune cellular functions that control pathogenic microbes; however, the mechanisms are poorly understood. Our aim was to determine the immunological consequences of increased ROS levels during acute bacterial infection. Results: We used a model of Streptococcus pneumoniae (Spn) lung infection and superoxide dismutase 3-deficient (SOD3-/-) mice, as SOD3 is a major antioxidant enzyme that catalyses the dismutation of superoxide radicals. First, we observed that in vitro, macrophages from SOD3-/- mice generated excessive phagosomal ROS during acute bacterial infection. In vivo, there was a significant reduction in infiltrating neutrophils in the bronchoalveolar lavage fluid and reduced peribronchial and alveoli inflammation in SOD3-/- mice 2 days after Spn infection. Annexin V/propidium iodide staining revealed enhanced apoptosis in neutrophils from Spn-infected SOD3-/- mice. In addition, SOD3-/- mice showed an altered macrophage phenotypic profile, with markedly diminished recruitment of monocytes (CD11clo, CD11bhi) in the airways. Further investigation revealed significantly lower levels of the monocyte chemokine CCL-2, and cytokines IL-23, IL-1β, and IL-17A in Spn-infected SOD3-/- mice. There were also significantly fewer IL-17A-expressing gamma-delta T cells (γδ T cells) in the lungs of Spn-infected SOD3-/- mice. Innovation: Our data demonstrate that SOD3 deficiency leads to an accumulation of phagosomal ROS levels that initiate early neutrophil apoptosis during pneumococcal infection. Consequent to these events, there was a failure to initiate innate γδ T cell responses. Conclusion: These studies offer new cellular and mechanistic insights into how excessive ROS can regulate innate immune responses to bacterial infection.

BACKGROUND. Patients often seek consultation with dentists for temporomandibular disorders (TMDs). The objectives of this article were to describe the methods of a large prospective cohort study of painful TMD management, practitioners’ and patients’ characteristics, and practitioners’ initial treatment recommendations conducted by The National Dental Practice-Based Research Network (the “network”). METHODS. Participating dentists recruited into this study treated patients seeking treatment for painful TMDs. The authors developed self-report instruments based on well-accepted instruments. The authors collected demographics, biopsychosocial characteristics, TMD symptoms, diagnoses, treatments, treatment adherence, and painful TMDs and jaw function outcomes through 6 months. RESULTS. Participating dentists were predominately White (76.8%) and male (62.2%), had a mean age of 52 years, and were general practitioners (73.5%) with 23.8% having completed an orofacial pain residency. Of the 1,901 patients with painful TMDs recruited, the predominant demographics were White (84.3%) and female (83.3%). Patients’ mean age was 44 years, 88.8% self-reported good to excellent health, and 85.9% had education beyond high school. Eighty-two percent had pain or stiffness of the jaw on awakening, and 40.3% had low-intensity pain. The most frequent diagnoses were myalgia (72.4%) and headache attributed to TMDs (51.0%). Self-care instruction (89.4%), intraoral appliances (75.4%), and medications (57.6%) were recommended frequently. CONCLUSIONS. The characteristics of this TMD cohort include those typical of US patients with painful TMDs. Network practitioners typically managed TMDs using conservative treatments. PRACTICAL IMPLICATIONS. This study provides credible data regarding painful TMDs and TMD management provided by network practitioners across the United States. Knowledge acquired of treatment recommendations and patient reports may support future research and improve dental school curricula.

BackgroundStudies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort.MethodsPatients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis.ResultsOf 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses.ConclusionThis analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

The solar receiver is the most important component of any central solar tower power plant (CSP) system. A numerical analysis of four billboard geometry designs of the central tower receiver was undertaken in this study. On the receiver, the surface area, heat transfer fluid (HTF), and intensity of beam radiation were all constant. The mass flow rate of HTF was modified, and the temperature gain was used as a metric to determine the most efficient design based on the analytical results. Four different models of vertical tube receivers were designed and analyzed. In the analysis, the surface area of the receivers was the same. When compared to the vertical variable circular tube receiver design, the vertical variable hexagonal tube receiver design achieved a marginally higher temperature for the HTF fluid at lower mass flow rates.

Diversity and phenology of host-seeking ticks were studied in the Flint Hills region of the USA, which is a prominent region for raising beef cattle. Between a two-year period from 2015–2017, ticks were collected using the dragging method from 9 distant locations, 6 of which were studied seasonally and 3 continuously throughout the study period. Of the 10,055 ticks collected, 76.5% were the Lonestar tick (Amblyomma americanum), 14% were American dog tick (Dermacentor variabilis), and 9.1% were Gulf Coast tick (A. maculatum). The blacklegged tick, Ixodes scapularis were also found, albeit in low numbers. The host-seeking activity of all three predominant tick species peaked once during the late spring, summer months in the region. The phenology of all ticks was positively associated with accumulated temperature and photoperiod. Additionally, the Normalized Vegetation Difference Index (NDVI) was associated with A. americanum, and saturation deficit and relative humidity were negatively associated with D. variabilis and A. maculatum tick phenology, respectively. This finding is useful to predict the times during a year in which cattle are at higher risk for exposure to these ticks and associated pathogens.

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.

Influenza is a common and contagious respiratory disease caused by influenza A, B, C, and D viruses (IAV, IBV, ICV, and IDV). A multiplex real-time RT-PCR assay was developed for simultaneous detection of IAV, IBV, ICV, and IDV. The assay was designed to target unique sequences in the matrix gene of IBV and ICV, the RNA polymerase subunit PB1 of IDV, and combined with USDA and CDC IAV assays, both target the matrix gene. The host 18S rRNA gene was included as an internal control. In silico analyses indicated high strain coverages: 97.9% for IBV, 99.5% for ICV, and 100% for IDV. Transcribed RNA, viral isolates and clinical samples were used for validation. The assay specifically detected target viruses without cross-reactivity, nor detection of other common pathogens. The limit of detection was approximately 30 copies for each viral RNA template, which was equivalent to a threshold cycle value of ~37.

Highlights • A multiplex real-time PCR assay was developed for PCV2 and PCV3 detection and differentiation. • Sensitivity was determined by standard curves with viral isolates and positive diagnostic samples. • Specificity was determined by testing common swine viruses. • The assay was validated on 336 swine diagnostic samples. • Limited data indicated that PCV3 has higher prevalence than PCV2 in the US., A multiplex quantitative real-time polymerase chain reaction (mqPCR) assay was developed and validated for the detection and differentiation of porcine circovirus type 3 (PCV3) and type 2 (PCV2) strains. The assay coverage was 97.9% (184/188) for PCV3 and 99.1% (1889/1907) for PCV2 sequences that were available from the current GenBank database. The PCR amplification efficiencies were 98–99% for plasmids, and 92–96% for diagnostic samples, with correlation coefficients all greater than 0.99. The limit of detection (LOD) determined as plasmid copies per reaction was 17 for PCV3 and 14 for PCV2. The assay specifically detected the targeted viruses without cross reacting to each other or to other common porcine viruses. Among 336 swine clinical samples collected in 2018, 101 (30.1%) were PCV3 positive, 56 (16.7%) were PCV2 positive and 18 (5.4%) were co-positives. Sixty selected PCV3 positives were confirmed by Sanger sequencing, and 53 of the 56 PCV2 positive samples were tested positive by another validated PCR assay.

The last 30 years of school reform have left us with an increase in urban school districts with market regimes (school choice, charter schools, and managerialism). Sociologists of the professions h...

Between March 2014 and February 2017, host-seeking ticks were collected during the late spring and summer months seasonally, and as well as continually through all seasons from several sites in a periurban environment in Pittsburg, Kansas, located in the Central Midwestern United States. All three post-emergent life-stages of Amblyomma americanum, and the adults of three other ticks viz. Dermacentor variabilis, A. maculatum, and Ixodes scapularis were collected using the flagging method, and were taxonomically identified using morphological and molecular methods. A total of 15946 ticks were collected from these sites. A vast majority of the ticks collected over the three-year study period was A. americanum (79.01%). The three other species collected included D. variabilis (13.10%), A. maculatum (7.15%), and Ixodes scapularis (0.73%). More female ticks of each species were collected throughout the study period from all sites, and a unimodal activity period was noted for all four species. The diversity, composition, and phenology of these medically significant tick species are discussed.

BackgroundDental procedures often produce aerosols and splatter which have the potential to transmit pathogens such as SARS-CoV-2. The existing literature is limited.MethodsAerosols and splatter were generated from an ultrasonic scaling procedure on a dental mannequin and characterized by two optical imaging methods – digital inline holography (DIH) and laser sheet imaging (LSI). Capture efficiencies of various aerosol mitigation devices were evaluated and compared.ResultsThe ultrasonic scaling procedure generates a wide size range of aerosols up to a few hundred micrometers and occasional large splatter which emit at low velocity (mostly below 3 m/s). Use of a saliva ejector (SE) and high-volume evacuator (HVE) resulted in 63% and 88% of overall reduction respectively while an extraoral local extractor (ELE) resulted in a reduction of 96% at the nominal design flow setting.ConclusionsThe study results showed that the use of ELE or HVE significantly reduced aerosol and splatter emission. The use of HVE generally requires an additional person to assist a hygienist, while an ELE can be operated “hands-free” when a dental hygienist is performing ultrasonic scaling and other operations.Practical ImplicationsAn extraoral local extractor aids in the reduction of aerosols and splatters during ultrasonic scaling procedures, potentially reducing transmission of oral or respiratory pathogens, like SARS-CoV-2. Position and airflow of the device are important to effective aerosol mitigation.

COPD and idiopathic pulmonary fibrosis (IPF) together represent a considerable unmet medical need, and advances in their treatment lag well behind those of other chronic conditions. Both diseases involve maladaptive repair mechanisms leading to progressive and irreversible damage. However, our understanding of the complex underlying disease mechanisms is incomplete; with current diagnostic approaches, COPD and IPF are often discovered at an advanced stage and existing definitions of COPD and IPF can be misleading. To halt or reverse disease progression and achieve lung regeneration, there is a need for earlier identification and treatment of these diseases. A precision medicine approach to treatment is also important, involving the recognition of disease subtypes, or endotypes, according to underlying disease mechanisms, rather than the current “one-size-fits-all” approach. This review is based on discussions at a meeting involving 38 leading global experts in chronic lung disease mechanisms, and describes advances in the understanding of the pathology and molecular mechanisms of COPD and IPF to identify potential targets for reversing disease degeneration and promoting tissue repair and lung regeneration. We also discuss limitations of existing disease measures, technical advances in understanding disease pathology, and novel methods for targeted drug delivery.

Unexpected questing activity of ticks was noted during the winter months of January and February in the Central Midwestern states of Kansas, Missouri, Oklahoma, and Arkansas. From nine geographically distinct locations, four species of ticks were collected using the flagging method, of which the lone star tick, Amblyomma americanum, was most abundant, followed by the American dog tick, Dermacentor variabilis, the Gulf coast tick, Amblyomma maculatum, and the Black legged tick, Ixodes scapularis. More A. americanum nymphs were caught questing than male or female adults. The winter activity of these medically important ticks in this region poses concern for public health and offers an insight into future tick activity in light of ongoing climate change. More studies on the seasonality of these tick species, and how different climate parameters affect their seasonal activity in this region are warranted and would be expected to benefit for both human and veterinary medicine.

Background: Blood eosinophil count (bEOS) is an important biomarker in obstructive lung disease. NOVELTY (NCT02760329) is a global, prospective, observational study with potential to identify obstructive lung disease phenotypes associated with differential outcomes, using biomarkers and clinical features. Objective: To evaluate factors associated with bEOS in patients with either physician-assigned asthma or COPD in NOVELTY. Methods: A cross-sectional analysis of associations between a single bEOS measurement and other baseline characteristics was performed using univariate and multivariate regression models. Results: Of 4,538 patients with data, the geometric mean (SE) bEOS was 0.16 (0.002) x109/L. Of these, 864 (19%) had EOS ≥300 cells/µL (23% asthma; 14% COPD). High bEOS was positively associated with male sex, ≥2 symptom worsenings in prior 3 months, FeNO, FEV1 reversibility, obesity and frequent mucoid cough, in both asthma and COPD (Figure). For asthma, positive associations with higher bEOS were observed for reduced lung function and physician-assessed severity; for COPD, positive associations were observed with current/former smokers. Associations with FeNO and frequent mucoid cough persisted in multivariate models for both diagnoses. Conclusions: Higher bEOS was independently associated with higher FeNO and presence of frequent mucoid cough regardless of physician-assigned asthma or COPD.

Background: Determinates of how physicians assign severity in asthma or COPD are poorly understood. The NOVEL observational longiTudinal studY NOVELTY (NCT02760329) is a global, prospective, 3-year observational study of patients with a physician-assigned diagnosis or suspected diagnosis of asthma, asthma+COPD or COPD. Objective: To identify factors associated with physician-assigned severity of either asthma or COPD in the NOVELTY population. Methods: Ordinal regression analysis was used to identify factors associated with higher physician-assigned severity (severe vs mild or moderate; moderate vs mild) at baseline in patients with asthma (n=4,361) or COPD (n=2,931). Results: Factors associated with higher levels of physician-assigned severity are shown in the figure. Clinical features including exacerbation history in the past year, lower post-bronchodilator FEV1 % predicted, or FEV1/FVC ratio, reversibility and higher mMRC dyspnoea score were associated with greater severity for both diagnoses. Presence of allergic or non-allergic rhinitis or nasal polyps were notable factors in asthma, as was emphysema in COPD. Conclusions: Greater physician-assigned severity was associated with worse respiratory symptoms, lower lung function and exacerbation history in patients with asthma or COPD in NOVELTY; associations between greater severity and some diagnosis-related features and comorbidities varied between asthma and COPD.