Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma

The Lantern Vol. 54, No. 2, Spring 1988

• Burning the Christmas Guests • A Song in Time • I Ask a Question • As If Raggedy Anne • One Man\u27s Escape • Gypsy Caravan • Apartment 14B • The College Inferno • Somewhere Under Manhattan • Trumped • Sunday • In Quest of Creativity • Imperfect Healing • The Game • The Hunger • Peanuts on the Beach • Battlefield Prom • Confessions of the Untrained Eye • Animal Attraction • Street Lamps • Hey, Old Man • In Search of Self-Actualization • Cousin Joe Bob\u27s First Visit to Pulsationshttps://digitalcommons.ursinus.edu/lantern/1132/thumbnail.jp

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

Does the Osteopathic Pedal Pump Reduce Lower Limb Volume in Healthy Subjects?

CONTEXT: Lymphatic treatments are gentle and passive techniques believed to enhance movement of lymph back into the central circulatory system. Animal studies provide supportive evidence, yet there are few studies in humans. OBJECTIVES: The aim of this study is to investigate whether the osteopathic pedal pump protocol reduces volume in the lower limbs of healthy subjects. METHODS: A total of 30 first- and second-year medical students were recruited. Subjects were excluded from participating if they had acute asthma, chronic obstructive pulmonary disease (COPD), congestive heart failure, active infections, fractures of the lower extremities, or metastatic cancer. A within-subjects study design with pre- and posttreatment measurement of lower limb volume was utilized. Pretreatment lower limb volume measurements were obtained utilizing a volumetric water gauge prior to myofascial thoracic inlet release and a 5 min pedal lymphatic pump protocol treatment. Posttreatment lower limb measurements were taken immediately following the protocol treatment. A telephone interview was conducted 2-3 days after the treatment to assess the participants\u27 experience of the treatment and whether the treatment elicited a subjective change from baseline. A paired t test was utilized to determine the statistical significance of volume displacement posttreatment. RESULTS: The mean change of pretreatment to posttreatment lower limb volume was -45.63 mL with a standard deviation of 37.65 mL. The change between the pretreatment and posttreatment volume measurements was statistically significant (p CONCLUSIONS: The osteopathic pedal pump technique, when utilized on those without leg lymphedema, reduces lower limb volume as measured by the volumetric water gauge. Further studies are warranted, especially in persons with excess lower-extremity edema, lymphedema or venous stasis

Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection

Intracellular pathogens belonging to the genus Leishmania have developed effective strategies that enable them to survive within host immune cells. Immunostimulatory compounds that counteract such immunological escape mechanisms represent promising treatment options for diseases. Here, we demonstrate that a lipopeptidephosphoglycan (LPPG) isolated from the membrane of a protozoan parasite, Entamoeba histolytica (Eh), shows considerable immunostimulatory effects targeted against Leishmania (L.) major, a representative species responsible for cutaneous leishmaniasis (CL). Treatment led to a marked reduction in the number of intracellular Leishmania parasites in vitro, and ameliorated CL in a mouse model. We next designed and synthesized analogs of the phosphatidylinositol anchors harbored by EhLPPG; two of these analogs reproduced the anti-leishmanial activity of the native compound by inducing production of pro-inflammatory cytokines. The use of such compounds, either alone or as a supportive option, might improve the currently unsatisfactory treatment of CL and other diseases caused by pathogen-manipulated immune responses

Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1

Altered monocyte responses and testosterone levels correlate, individually, with the pathogenesis of hepatic amebiasis in mice. Here the authors show that testosterone induces enhanced TNF/CXCL1 expression and stronger proinflammatory responses in both human and mouse monocytes to support an androgen-monocyte axis of inflammation regulation

Indemnifying against flood loss in a changing environment

The UK – as with all other parts of the globe - is faced with new environmental uncertainties, particularly from climate change. Factors which threaten its existing flood loss indemnity regime regarding damage to property include greater ecological awareness on the part of policy makers, pressures to limit public commitments to flood defence, and the growing technical ability of insurers to distinguish risk exposure across particular locations. Current reliance on the commercial insurance market is called into question, as general levels of insurance availability and affordability come under threat. Problems of take-up among particular groups will be exacerbated by more restricted availability or terms of cover which are likely increasingly to affect vulnerable individuals and communities. The changing law and policy environment involves challenges to the delicate public-private balance which has underpinned the current arrangements and has implications both for civil society and the insurance industry, as well as informing the extent to which alternative approaches might offer solutions