Search

Context Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4). Objective To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4. Methods Single-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg). Results Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (P Conclusion GLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.

Here, we present the first draft genome sequences of 10 bacterial strains that were isolated from the rumen, nasopharynx, vagina, or uterus of healthy beef cattle. These genomes are from one Alkalihalobacillus clausii isolate, three Bacillus safensis isolates, five Escherichia coli isolates, and one Pasteurella multocida isolate.

To support all students, including students with disabilities, many schools have adopted a positive behavioral interventions and supports (PBIS) framework. Although rigorous research documents the beneficial effects of Tier 1 PBIS for all students and emerging research extends these findings to students with disabilities, there has not been a national U.S. study focused on PBIS and discipline outcomes for students with disabilities. In this exploratory study, we combine existing national data sets to explore the relationship between (a) known PBIS exposure (i.e., being in the PBIS data set) and fidelity (i.e., meeting the criterion on an established fidelity measure of Tier 1 PBIS) and (b) exclusionary discipline for students with disabilities. Using two-part path analysis, we document that PBIS may be associated with decreased use of suspension; however, findings are less consistent for other discipline outcomes. This study highlights the critical need for more accurate data on discipline outcomes and further research on effective intervention.

PurposeDespite immigrant-receiving countries' need for skilled professionals to meet labour demands, research suggests that many skilled migrants undergo deskilling, downward career mobility, underemployment, unemployment and talent waste, finding themselves in low-skilled occupations that are not commensurate to their education and experience. Skilled immigrant women face additional gendered disadvantages, including a disproportionate domestic burden, interrupted careers and gender segmentation in occupations and organizations. This study explores how the ongoing COVID-19 pandemic impacted skilled newcomer women's labour market outcomes and work experiences.Design/methodology/approachThe authors draw on 50 in-depth questionnaires with skilled women to elaborate on their work experiences during the ongoing COVID-19 pandemic.FindingsThe pandemic pushed skilled immigrant women towards unemployment, lower-skilled or less stable employment. Most study participants had their career trajectory delayed, interrupted or reversed due to layoffs, decreased job opportunities and increased domestic burden. The pandemic's gendered nature and the reliance on work-from-home arrangements and online job search heightened immigrant women's challenges due to limited social support and increased family responsibilities.Originality/valueThis paper adds to the conversation of increased integration challenges under pandemic conditions by contextualizing the pre-pandemic literature on immigrant work integration to the pandemic environment. Also, this paper contributes a better understanding of the gender dynamics informing the COVID-19 socio-economic climate.

The purpose of this longitudinal study was to examine patterns in implementation of Tiers 2 and 3 school-wide positive behavioral interventions and supports (SWPBIS) systems to identify timings of installation that led to higher implementation of advanced tiers. Extant data from 776 schools in 27 states reporting on the first 3 years of Tier 2 implementation and 359 schools in 23 states reporting on the first year of Tier 3 implementation were analyzed. Using structural equation modeling, we found that higher Tier 1 implementation predicted subsequent Tier 2 and Tier 3 implementation. In addition, waiting 2 or 3 years after initial Tier 1 implementation to launch Tier 2 systems predicted higher initial Tier 2 implementation (compared with implementing the next year). Finally, we found that launching Tier 3 systems after Tier 2 systems, compared with launching both tiers simultaneously, predicted higher Tier 2 implementation in the second and third year, so long as Tier 3 systems were launched within 3 years of Tier 2 systems. These findings provide empirical guidance for when to launch Tiers 2 and 3 systems; however, we emphasize that delays in launching advanced systems should not equate to delays in more intensive supports for students.

Nitrogen (N) fertilizer runoff in the Mississippi River Basin contributes to a hypoxic zone in the Gulf of Mexico. Through efforts such as the Illinois Nutrient Loss Reduction Strategy, farmers are being challenged to voluntarily change production practices to limit the amount of N lost from their fields through runoff. Best management practices currently recommended to reduce nutrient loss include cover crops, optimal application timing, bioreactors, wetlands, and buffers. However, the adoption of new or unfamiliar farming practices such as these best management practices is inherently risky for farmers. In order to gain a more detailed understanding of how farmers perceive nutrient loss, and their willingness to voluntarily comply with nutrient loss reduction goals, a survey was designed and administered to approximately 3,850 members of the Illinois Corn Growers Association. The survey was designed in consultation with nutrient loss experts at the Illinois Corn Growers Association, whose membership was chosen because they would be most affected by regulation limiting N application timing or rates. Questions addressed farmers’ demographics, nutrient loss concerns, and production practices related to reducing nutrient loss. Key findings from the 762 completed surveys include the importance placed on conservation practices in respondents’ farming operations, a high level of concern about nutrient loss, and operational changes already made in response to those concerns. By providing insights on how farmers perceive and are responding to nutrient runoff, this study can contribute to efforts encouraging voluntary compliance with the goals of the Illinois Nutrient Loss Reduction Strategy.

Ranolazine reduces angina frequency and increases exercise capacity. We hypothesized that exercise training with ranolazine would allow subjects to train at greater intensities, resulting in greater improvements in exercise capacity, physical activity, and health-related quality of life (HRQOL). In a pilot study, subjects with chronic stable angina pectoris were randomized to ranolazine (n = 13) or placebo (n = 16). After a 2-week drug titration period, subjects participated in a 12-week exercise program. Peak VO2, physical activity (via accelerometer), and HRQOL were assessed before and after training. After exercise training, peak VO2increased twice as much with ranolazine (2.1 ± 3.4 ml/kg/min) as with placebo (0.9 ± 1.5) (both p

Fidelity of implementation of school practices is crucial to student outcomes. Several types of tools, including self-assessments, are available for measuring fidelity, but little is known regarding the relation of self-assessments of fidelity to fidelity instruments completed with the support of external experts, specifically, during the first few years of implementation. The present study used cross-sectional data from 1,438 schools to examine relations between fidelity self-assessment and team-based fidelity measures in the first 4 years of implementation of School-Wide Positive Behavioral Interventions and Supports (SWPBIS). Results showed strong positive correlations between fidelity self-assessments and a team-based measure of fidelity at each year of implementation.

Although there is a plethora of information available regarding the impact of nutrition on exercise performance, many recommendations are based on male needs due to the dominance of male participation in the nutrition and exercise science literature. Female participation in sport and exercise is prevalent, making it vital for guidelines to address the sex-specific nutritional needs. Female hormonal levels, such as estrogen and progesterone, fluctuate throughout the mensural cycle and lifecycle requiring more attention for effective nutritional considerations. Sex-specific nutritional recommendations and guidelines for the active female and female athlete have been lacking to date and warrant further consideration. This review provides a practical overview of key physiological and nutritional considerations for the active female. Available literature regarding sex-specific nutrition and dietary supplement guidelines for women has been synthesized, offering evidenced-based practical information that can be incorporated into the daily lives of women to improve performance, body composition, and overall health.

The initial purpose of this study was to examine the effects of single-joint resistance exercise on NIRS measurements, tumor necrosis percentage, functionality, and the rate of wound complications in patients with STS of the extremities undergoing preoperative radiation. Due to extraneous circumstances, only two patients were able to complete study-related activities; therefore, the revised purpose of this preliminary study was to report demographic data on all parameters and assess the feasibility of the current protocol in order to guide subsequent research. Although no statistical analyses were performed, exercised-induced changes in blood volume were reported. Feasibility was evaluated on 8 established benchmarks: acceptability, demand, implementation, practicality, adaptation, integration, expansion, and limited-efficacy testing. Ultimately, it was determined that the current protocol is feasible for patients with soft tissue sarcoma below the knee in the lower limb.

Additional file of Sex differences and considerations for female specific nutritional strategies: a narrative review

Neutrophil dysfunction is a common feature of aging, and is associated with the pathogenesis of many age-related diseases, including type 2 diabetes mellitus (T2DM). Although exercise training improves metabolic health, decreases risk of T2DM, and is associated with improving neutrophil functions, involvement in regular physical activity declines with age. The aim of this study was to determine if neutrophil functions could be improved in association with changes in fitness and metabolic parameters in older adults at risk for T2DM using 10-weeks of low volume high-intensity interval exercise training (HIIT). Ten older (71 ± 5 years) sedentary adults with prediabetes (HbA1c: 6.1 ± 0.3%) completed 10 weeks of a supervised HIIT program. Three 30 min sessions/week consisted of ten 60 s intervals of low intensity [50–60% heart rate reserve (HRR)] separated with similar durations of high intensity intervals (80–90% HRR). Before and after training, glucose and insulin sensitivity, neutrophil chemotaxis, bacterial phagocytosis, reactive oxygen species (ROS) production, and mitochondrial functions were assessed. Exercise-mediated changes in cardiorespiratory fitness (VO2peak) and neutrophil functions were compared to six young (23 ± 1 years) healthy adults. Following training, significant reductions in fasting glucose and insulin were accompanied by improved glucose control and insulin sensitivity (all p < 0.05). Before exercise training, VO2peak in the old participants was significantly less than that of the young controls (p < 0.001), but increased by 16 ± 11% following training (p = 0.002) resulting in a 6% improvement of the deficit. Neutrophil chemotaxis, phagocytosis and stimulated ROS production were significantly less than that of the young controls, while basal ROS were higher before training (all p < 0.05). Following training, chemotaxis, phagocytosis and stimulated ROS increased while basal ROS decreased, similar to levels observed in the young controls (all p < 0.05) and reducing the deficit of the young controls between 2 and 154%. In five of the adults with prediabetes, neutrophil mitochondrial functions were significantly poorer than the six young controls before training. Following training, mitochondrial functions improved toward those observed in young controls (all p < 0.05), reducing the deficit of the young controls between 14.3 and 451%. Ten weeks of HIIT in older adults at risk for T2DM reduced disease risk accompanied by improved primary and bioenergetic neutrophil functions. Our results are consistent with a reduced risk of infections mediated by relationships in exercise induced systemic and cellular metabolic features.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02441205, registered on May 12th, 2015.

Background Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program. Methods Previously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod®) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1β), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-α), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships. Results Exercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO2) correlated with reductions in galectin-3 (r = −0.57, P = 0.05 in RA; r = −0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-α (r < −0.60 and P

In this 3-year prospective study, we tested the extent to which school-, practice-, and district-level variables predicted sustained implementation for schools in various stages of implementation of school-wide positive behavioral interventions and supports (SWPBIS) Tier 1 (universal) systems. Staff from 860 schools in 14 U.S. states completed a research-validated measure of factors associated with sustained implementation of school interventions during Year 1 of this study. Analyses included multigroup structural equation modeling of school and district implementation fidelity data. Results indicated that adequate implementation fidelity and better Team Use of Data for decision making in Study Year 1 were the strongest predictors of sustained implementation in Year 3. In addition, the number of other schools in the district adopting SWPBIS was a similarly strong predictor. A critical mass of schools implementing was also predictive, especially for schools earlier in implementation. School characteristics were not predictive, except for grade levels served, which was an inconsistent predictor by stage.

Aging in the right place (AIRP) involves supporting older adults to live as long as possible in their homes and communities, recognizing that where an older person lives impacts their ability to age optimally and must match their unique lifestyles and vulnerabilities. Photovoice, a participatory action research strategy, allows people to document their experiences through photography, promoting critical dialogue about issues such as AIRP and rights-based housing. This presentation highlights the concept of AIRP from the perspectives of a diverse group of older adults living in promising practices shelters in Vancouver, Montreal, and Calgary, Canada using photovoice. Findings indicate that the process promoted a sense of empowerment among participants. Insights about older adults’ perceptions of AIRP residing in shelters to best meet their intersectional identities, housing, and support needs will be shared. Findings inform policy initiatives that promote AIRP and the right to adequate housing for older adults experiencing homelessness.

Several reliable and valid fidelity surveys are commonly used to assess Tier 1 implementation in School-Wide Positive Behavioral Interventions and Supports (SWPBIS); however, differences across sur...

Feeding schedules are an important aspect of any husbandry regime for animals in human care. While frequently debated for endothermic animals, ectotherms, especially snakes, often suffer from stagnated animal husbandry practices. To rectify this issue, we investigated the impact of food presentation frequency, as well as food amount per presentation on the growth of one-year-old and newborn Corn Snakes (Pantherophis guttatus) and newborn False Water Cobras (Hydrodynastes gigas) in human care. Three cohorts, each composed of siblings, were split into two treatment groups for the experiment. Each snake was fed two prey items representing less than 5% of their mass, approximately three days apart over a 15 week period. All animals were weighed weekly in grams. Treatment 1 received both prey items on the same day while treatment 2 received one prey item a day for 2 consecutive days. Over a 7 day period each individual consumed the same amount of food. The goal of this study was to test the impact of energy allocation on digestion and to determine if the digestion of a single large meal resulted in a loss of energy allocation for growth. Results indicated that there was not a major difference in growth between treatments, suggesting that energy allocated for digesting large amounts of prey did not result in a loss of energy allocation for growth.

This study examines predictors of abandonment of evidence-based practices through descriptive analyses of extant state-level training data, fidelity of implementation data, and nationally reported school demographic data across 915 schools in three states implementing school-wide positive behavioral interventions and supports (SWPBIS). Schools included in this study were tracked for a 5-year period after initial training, yet some elected to abandon SWPBIS at various times during implementation. Results showed that a small proportion of schools in the sample abandoned SWPBIS (7%). Logistic regression analysis identified school locale as the only statistically significant predictor of SWPBIS abandonment with schools located in cities being more likely to abandon. Results are discussed in terms of addressing types of schools at greater risk for abandonment and the importance of state-level training and coaching support.

The purpose of this study was to document within-year fidelity growth during installation and initial implementation of School-Wide Positive Behavioral Interventions and Supports (SWPBIS). Participants included school teams from schools throughout the United States that were in years 1 to 4 of SWPBIS implementation and routinely evaluated their implementation fidelity. The fidelity outcome was assessed with the Team Implementation Checklist (TIC) and was completed multiple times per year by SWPBIS teams. Results from multilevel fidelity growth models documented within- and between-school variability and growth predictors. Years implementing, location, school type, and enrollment size were significant predictors of beginning-year fidelity scores (intercept), and years implementing and relative socioeconomic status were significant predictors of the average rate of fidelity change per month of school (slope). These results add to the growing field of implementation science, and practice recommendations are outlined. (PsycINFO Database Record

In this analysis of extant data from 3,011 schools implementing school-wide positive behavioral interventions and supports (SWPBIS) across multiple years, we assessed the predictive power of various school characteristics and speed of initial implementation on sustained fidelity of implementation of SWPBIS at 1, 3, and 5 years. In addition, we partitioned variance in whether schools sustained SWPBIS at the school, district, and state levels. Results showed that the largest differences in fidelity were at the state level. In addition, school characteristics (particularly grade levels served) and speed of initial implementation were significant but small predictors of sustained implementation. Results are discussed in terms of effective supports at the state and district levels, as well as addressing types of schools at greater risk of abandonment, such as high schools.

The purpose of this study was to determine if an experimental five-item measure of barriers to implementing and sustaining school-wide prevention practices, the Assessment of Barriers to Implementation and Sustainability in Schools (ABISS), would relate to objective measures of school-wide positive behavioral interventions and supports (SWPBIS) implementation fidelity. The ABISS was administered to individuals in 704 U.S. schools implementing SWPBIS across 11 states, and scores were compared with school demographic variables and SWPBIS fidelity of implementation. Results showed acceptable model fit for the ABISS, partial measurement invariance, and statistically significant relations, after controlling for school demographic variables, with SWPBIS fidelity of implementation, except for schools implementing SWPBIS for 5 or more years. These patterns indicate substantial but decreasing relations of perceived barriers to implementation fidelity as schools continue to implement SWPBIS. Implications are discussed in terms of how assessment of perceived barriers can support implementation and sustainability of school-wide prevention practices.

This essay examines the democratic impulses that shaped Thomas Paine’s vision for a religious revolution. Many historical treatments have recognized the central role that the themes of equality and freedom played in his political ideology. This study expands on this analysis by demonstrating how Paine grounded his religious beliefs in the same soil, advocating for Americans to extend the same democratic ideals of the political revolution to reform religion. Despite the irony that most Americans who supported Paine’s political vision rejected his religious ideas, many orthodox religious leaders adapted their beliefs and practices to the same democratic impulses as Paine. Thus, contrary to many treatments that simplistically juxtapose Paine and America’s faithful, this essay contends that both ultimately contributed to many of the same underlying democratic shifts in religious and cultural authority in late eighteenth- and early nineteenth-century America. Keywords: United States, Thomas Paine, American religion, democracy, evangelicalism DOI: 10.14712/23363231.2016.1

Recent research in implementation science has focused on identifying factors that predict adoption of evidence-based practices in schools. Less attention has focused on examining the adoption of practices within districts. This study included a sequential cohort of 552 districts in 25 U.S. states adopting an evidence-based framework, school-wide positive behavioral interventions and supports (PBIS). We examined schools within districts reporting on PBIS fidelity during their first five years of PBIS initiatives. Latent change score and multi-level growth modeling were used to examine and predict the percent of district adoption of PBIS over time. Results showed a significant increase in the rate of district adoption over the first 4 years of the initiative, with a decrease in growth between years 4 and 5. District size, proportion of students receiving free or reduced lunch, and districts located in cities and towns were found to be significant predictors of the percent of schools adopting PBIS. Implications for future implementation research and strategies for increasing the adoption of PBIS are discussed.

Jan Stievermann and Ryan P. Hoselton consider the role of experiential piety in the exegesis of Cotton Mather and Jonathan Edwards. Both were deeply engaged in the new critical questions of their day, and both were also committed to nurturing religious piety—though they differed somewhat in how they handled these concerns. Although Mather was profoundly interested in the philological and historical issues in the Bible, he prioritized devotional and contemplative engagement with Scripture. Edwards, Stievermann and Hoselton argue, drew on the experimental language and philosophy of the Enlightenment to construct a case for the supernatural authority of the Bible against increasingly naturalistic arguments. Edwards held that one gains spiritual understanding as the Holy Spirit harmonizes the believer’s internal senses with the Word; this reconstruction affected Edwards’ approach to the emotive element in Scripture, the dynamism of typology, and the nature of the regenerate interpreter of the Bible.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes.Methods: Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80–90% VO2reserve) separated by similar bouts of lower-intensity intervals (50–60% VO2reserve). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions.Results: Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p p p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p +)/CD16+ monocytes was reduced (p = 0.002), with both nonclassical (CD14dim/CD16bright) and intermediate (CD14bright/CD16positive) monocytes being reduced (both p p E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1β, IL-6, CXCL-8, IL-10, CRP, or TNF-α.Conclusions: We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.

Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive eosinophilic and lymphocytic inflammation with associated changes in the extracellular matrix (ECM) resulting in airway wall remodeling. Hyaluronan (HA) is a nonsulfated glycosaminoglycan ECM component that functions as a structural cushion in its high molecular mass (HMM) but has been implicated in metastasis and other disease processes when it is degraded to smaller fragments. However, relatively little is known about the role HA in mediating inflammatory responses in allergy and asthma. In the present study, we used a murine Aspergillus fumigatus inhalational model to mimic human disease. After observing in vivo that a robust B cell recruitment followed a massive eosinophilic egress to the lumen of the allergic lung and corresponded with the detection of low molecular mass HA (LMM HA), we examined the effect of HA on B cell chemotaxis and cytokine production in the ex vivo studies. We found that LMM HA functioned through a CD44-mediated mechanism to elicit chemotaxis of B lymphocytes, while high molecular mass HA (HMM HA) had little effect. LMM HA, but not HMM HA, also elicited the production of IL-10 and TGF-β1 in these cells. Taken together, these findings demonstrate a critical role for ECM components in mediating leukocyte migration and function which are critical to the maintenance of allergic inflammatory responses.

Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung.

Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. J(H)(-/-) mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, J(H)(-/-) mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and J(H)(-/-) mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of J(H)(-/-) mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the J(H)(-/-) animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.

Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive inflammation and remodeling of the extracellular matrix (ECM) and associated cells of the airway wall. Under inflammatory conditions, hyaluronan (HA), a major component of the ECM, undergoes dynamic changes, which may in turn affect the recruitment and activation of inflammatory cells leading to acute and chronic immunopathology of allergic asthma.In the present study, we measured the changes in HA levels generated at sites of inflammation, and examined its effect on inflammatory responses and collagen deposition in an Aspergillus fumigatus murine inhalational model of allergic asthma.We found that HA levels are elevated in allergic animals and that the increase correlated with the influx of inflammatory cells 5 days after the second allergen challenge. This increase in HA levels appeared largely due to upregulation of hyaluronidase-1 (HYAL1) and hyaluronidase-2 (HYAL2). Furthermore, HA co-localizes with areas of new collagen synthesis and deposition.Overall, our findings contribute to the growing literature that focuses on the components of ECM as inflammatory mediators rather than mere structural support products. The evidence of HA localization in fungal allergic asthma provides the impetus to study HA more closely with allergic leukocytes in murine models. Further studies examining HA's role in mediating cellular responses may help to develop targets for treatment in patients with severe asthma due to fungal sensitization.

Asthma was the most common comorbidity in hospitalized patients during the 2009 influenza pandemic. For unknown reasons, hospitalized asthmatics had less severe outcomes and were less likely to die from pandemic influenza. Our data with primary human bronchial cells indicate that changes intrinsic to epithelial cells in asthma may protect against cytopathology induced by influenza virus. To further study influenza virus pathogenesis in allergic hosts, we aimed to develop and characterize murine models of asthma and influenza comorbidity to determine structural, physiological and immunological changes induced by influenza in the context of asthma. Aspergillus fumigatus-sensitized and -challenged C57BL/6 mice were infected with pandemic H1N1 influenza virus, either during peak allergic inflammation or during airway remodeling to gain insight into disease pathogenesis. Mice infected with the influenza virus during peak allergic inflammation did not lose body weight and cleared the virus rapidly. These mice exhibited high eosinophilia, preserved airway epithelial cell integrity, increased mucus, reduced interferon response and increased insulin-like growth factor-1. In contrast, weight loss and viral replication kinetics in the mice that were infected during the late airway remodeling phase were equivalent to flu-only controls. These mice had neutrophils in the airways, damaged airway epithelial cells, less mucus production, increased interferons and decreased insulin-like growth factor-1. The state of the allergic airways at the time of influenza virus infection alters host responses against the virus. These murine models of asthma and influenza comorbidity may improve our understanding of the epidemiology and pathogenesis of viral infections in humans with asthma.

Extremely long, electrically conductive, ductile, free-standing nanosheets of water-stabilized KxCoO2·yH2O are synthesized using the sol-gel and electric-field induced kinetic-demixing (SGKD) process. Room temperature in-plane resistivity of the KxCoO2·yH2O nanosheets is less than ~4.7 mΩ·cm, which corresponds to one of the lowest resistivity values reported for metal oxide nanosheets. The synthesis produces tens of thousands of very high aspect ratio (50,000:50,000:1 = length/width/thickness), millimeter length nanosheets stacked into a macro-scale pellet. Free-standing nanosheets up to ~50 μm long are readily delaminated from the stacked nanosheets. High-resolution transmission electron microscopy (HR-TEM) studies of the free-standing nanosheets indicate that the delaminated pieces consist of individual nanosheet crystals that are turbostratically stacked. X-ray diffraction (XRD) studies confirm that the nanosheets are stacked in perfect registry along their c-axis. Scanning electron microscopy (SEM) based statistical analysis show that the average thickness of the nanosheets is ~13 nm. The nanosheets show ductility with a bending radius as small as ~5 nm.

Psychometric and utility studies on Social Emotional Assessment Measure (SEAM), an innovative tool for assessing and monitoring social-emotional and behavioral development in infants and toddlers with disabilities, were conducted. The Infant and Toddler SEAM intervals were the study focus, using mixed methods, including item response theory modeling and classical test theory. Results using a Rasch one-parameter logistic model indicated model fit statistics were consistent for age and item difficulty as well as for ability and item characteristics. Classical test theory analyses generally confirmed the developmental structure; mean scores increased with age and were significantly correlated across 6-month increments. Reliability studies indicated strong internal consistency and moderate interrater agreement between teachers. Test–retest reliability results completed by parents online indicated significant agreement. Overall, 90% of parents reported the SEAM asked appropriate questions and took less than 10 min to complete.

Allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. This study assessed the requirement for B cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. C57BL/6 and μMT mice (assumed to lack peripheral B cells) were sensitized with Aspergillus fumigatus extract and challenged with two inhalation exposures of live conidia to induce airway disease. Airway hyperresponsiveness after methacholine challenge, peribronchovascular inflammation, goblet cell metaplasia, and fibrotic remodeling of the airways was similar between μMT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the μ-chain, these μMT mice produced IgE and IgG Abs, although the Abs induced did not have specificity for A. fumigatus Ags. In contrast, IgA was not detected in either the lavage fluid or serum of μMT mice that had been exposed to A. fumigatus. Our findings also reveal the existence of CD19+CD9+IgD+ B-1 cells in the lungs of the μMT animals. These data show the μMT mice to have a developmental pathway independent of the canonical μ-chain route that allows for their survival upon antigenic challenge with A. fumigatus conidia, although this pathway does not seem to allow for the normal development of Ag-specific repertoires. Additionally, this study shows that IgA is not required for either clearance or containment of A. fumigatus in the murine lung, as fungal outgrowth was not observed in the μMT animals after multiple inhalation exposures to live conidia.

As part of efforts throughout China to improve the outcomes of individuals with disabilities, the Shanghai government has launched a campaign to screen at least 95 percent of newborns. To assist in meeting this goal, the Ages & Stages Questionnaires (ASQ), Third Edition, was translated into Chinese and the feasibility of a screening system using the ASQ-Chinese translation (ASQ-C) was investigated in Shanghai. Twenty-nine primary children’s healthcare clinics and several district-wide children’s healthcare institutes participated. Validity and reliability of the ASQ-C were studied as well as utility in pediatric clinics as part of well child visits. Using a sample of more than 8000 caregivers and children from 3 to 66 months of age, screening cutoff scores for each of the 19 ASQ-C intervals were determined, based on two standard deviations below the mean domain score. Inter-rater agreement between ASQ-C completed by 519 parents and a professional assessor was .89. Test-retest reliability for 651 caregivers who completed two ASQ-C at a 1–4 week interval was .91. Cronbach’s coefficient alpha measuring internal consistency ranged from .37 to .79. Convergent validity, measuring agreement between Bayley Scales of Infant Development, 2nd edition, and Denver II outcome categories (i.e. risk, typical) and ASQ-C outcomes (i.e. risk, typical), ranged from .57 to .94. Results from this pilot study suggest the ASQ-C is a promising screening instrument for identification of developmental problems in the Shanghai region. Implementation of a universal screening system in pediatric clinics has the potential to assist in early identification of developmental delays, referral to rehabilitative services, and improvement of developmental outcomes for young children and their families.

Fungal sensitization in patients with asthma often indicates an unusual disease course in which traditional asthma treatments have little effect and in which morbidity is particularly severe. Airway hyperresponsiveness (AHR), inflammatory infiltrates, smooth muscle hyperplasia, and irreversible fibrotic remodeling of the bronchial architecture are features of allergic fungal asthma. The systemic production of IgE has long been associated with the immunopathogenesis of allergic asthma; however, the role of B lymphocytes and their products in the response to fungal allergens remains unclear. In the present study, we hypothesize that B lymphocytes are recruited to the allergic lung to impact the allergic response. Using a murine fungal aeroallergen model to mimic the human syndrome, we characterized the B cell population in the lung after fungal challenge and found that CD19(+)CD23(+) B2 lymphocyte numbers are increased in the allergic lung in a dynamic process. IgA, IgG(2a), and IgE were prominent in the serum and bronchoalveolar lavage fluid of allergic animals. It was evident that a tissue-centric production of these antibodies was possible. IgA-, IgG-, and IgE-producing cells from the allergic lung were identified by flow cytometry and immunohistochemistry. This study shows for the first time that CD19(+)CD23(+) B2 lymphocyte numbers change in the lung in a dynamic process after inhalation of fungal conidia and their increase has a significant impact on the Ab production in the pulmonary compartment in the context of fungal allergy.

Fungal exposure may elicit a number of pulmonary diseases in man, including allergic asthma. Fungal sensitization is linked to asthma severity, although the basis for this increased pathology remains ambiguous. To create conditions simulating environmental fungal allergen exposure in a human, nose-only inhalation delivery of Aspergillus fumigatus conidia was employed in mice previously sensitized to Aspergillus antigen extract. BALB/c mice were immunized with subcutaneous and intraperitoneal injections of soluble A. fumigatus extract in alum, which was followed by three intranasal inoculations of the same fungal antigens dissolved in saline to elicit global sensitization in a manner similar to other published models. The animals were then challenged with a 10-min inhaled dose of live conidia blown directly from the surface of a mature A. fumigatus culture. After a single challenge with inhaled A. fumigatus conidia, allergic pulmonary inflammation and airway hyperresponsiveness were significantly increased above that of either naïve animals or animals that had been sensitized to A. fumigatus antigens but not challenged with conidia. The architecture of the lung was changed by inhalation of conidia when compared to controls in that there were significant increases in epithelial thickness, goblet cell metaplasia, and peribronchial collagen deposition. Additionally, α-smooth muscle actin staining of histological sections showed visual evidence of increased peribronchial smooth muscle mass after fungal challenge. In summary, the delivery of live A. fumigatus conidia to the sensitized airways of BALB/c mice advances the study of the pulmonary response to fungi by providing a more natural route of exposure and, for the first time, demonstrates the consistent development of fibrosis and smooth muscle changes accompanying exposure to inhaled fungal conidia in a mouse model.

The Aspergillus fumigatus mouse model of asthma mimics the characteristics of human fungal asthma, including local and systemic inflammation. Monocyte/macrophage lineage cells direct innate immune responses and guide adaptive responses. To identify gene expression changes in peripheral blood monocytes in the context of fungal allergy, mice were exposed to systemic and intranasal inoculations of fungal antigen (sensitized), and naive and sensitized animals were challenged intratracheally with live A. fumigatus conidia. Microarray analysis of blood monocytes from allergic versus non-allergic mice showed ≥ twofold modulation of 45 genes. Ingenuity pathway analysis revealed a network of these genes involved in antigen presentation, inflammation, and immune cell trafficking. These data show that allergen sensitization and challenge affects gene expression in peripheral monocytes.

Allergic asthma is a T(H)2-mediated disease marked by airway inflammation, increased mucus production, and elevated serum IgE in response to allergen provocation. Among its ascribed functions, the neuropeptide vasoactive intestinal peptide (VIP) is believed to promote a T(H)2 phenotype when signaling through its VPAC(2) receptor. In this study, we assessed the requirement for the VIP/VPAC(2) axis in initiating the allergic pulmonary phenotype in a murine model of fungal allergic asthma. C57BL/6 wild-type (WT) and VPAC(2) knock-out (KO) mice were sensitized with Aspergillus fumigatus antigen and challenged with an aerosol of live conidia to induce allergic airways disease. WT and KO mice exhibited similar peribronchovascular inflammation, increased number of goblet cells, and elevated serum IgE. However, the absence of VPAC(2) receptor resulted in a marked enhancement of MUC5AC mRNA with an associated increase in goblet cells and a reduction in eosinophils in the airway lumen at day 3 when VIP mRNA was undetectable in the KO lung. Sustained elevation of serum IgE was noted in KO mice at day 14, while the level in WT mice declined at this time point. These data suggest that the absence of VPAC(2) does not protect mice from developing the signs and symptoms of allergic asthma.

This study examined the accuracy of a curriculum-based assessment for use during the eligibility process for Individuals with Disabilities Education Improvement Act (IDEA) services. The study extended a previous investigation in which performance scores of children without disabilities on the Assessment, Evaluation, and Programming System (AEPS) were used to set cutoff scores at 6-month age intervals. These cutoff scores were then tested for service eligibility classification accuracy. The present study specifies and examines cutoff scores at more specific age intervals and performance domains. Present study findings largely replicated results of the original study. The AEPS cutoff scores were found to accurately classify most eligible children but did overidentify some ineligible children. The data from these two studies suggest that, to the extent allowed by state criteria, early intervention/early childhood special education personnel may be able to use the AEPS test as a valid assessment tool while qualifying children for IDEA services.

The inability to accurately mimic and track the natural mechanisms of sensitization, challenge, and clearance in experimental models of allergic asthma restricts the ability to identify potential therapeutic targets and elucidate basic biological mechanisms of this prominent human disease. Use of a clinically relevant fungal allergen, such as Aspergillus fumigatus, allows researchers to follow an allergen's uptake and clearance from the lung. Unfortunately, there are currently limited resources to specifically visualize or sensitively quantify a small number of fungal conidia in the lung. In this study, we have created and characterized an IgG1 isotype monoclonal antibody produced against the intact conidia of A. fumigatus for the purpose of developing specific detection and quantification techniques.

Although fungi are pervasive in many environments, few cause disease in humans. Of these, Aspergillus fumigatus is particularly well suited to be a pathogen of the human lung. Its physical and biological characteristics combine to provide an organism that can cause tremendous morbidity and high mortality if left unchecked. Luckily, that is rarely the case. However, repeated exposure to inhaled A. fumigatus spores often results in an immune response that carries significant immunopathology, exacerbating asthma and changing the structure of the lung with chronic impacts to pulmonary function. This review focuses on the current understanding of the mechanisms that are associated with fungal exposure, sensitization, and infection in asthmatics, as well as the function of various inflammatory cells associated with severe asthma with fungal sensitization.