Pathogenic Mannheimia haemolytica invades differentiated bovine airway epithelial cells

The Gram-negative bacterium Mannheimia haemolytica is the primary bacterial species associated with bovine respiratory disease (BRD) which is responsible for significant economic losses to the livestock industries worldwide. Healthy cattle are frequently colonised by commensal serotype A2 strains, but disease is usually caused by pathogenic strains of serotype A1. For reasons that are poorly understood, a transition occurs within the respiratory tract and a sudden explosive proliferation of serotype A1 bacteria leads to the onset of pneumonic disease. Very little is known about the interactions of M. haemolytica with airway epithelial cells of the respiratory mucosa which might explain the different abilities of serotype A1 and A2 strains to cause disease. In the present study, host-pathogen interactions in the bovine respiratory tract were mimicked using a novel differentiated bovine bronchial epithelial cell (BBEC) infection model. In this model, differentiated BBECs were inoculated with serotype A1 or A2 strains of M. haemolytica and the course of infection followed over a five-day period by microscopic assessment and measurement of key proinflammatory mediators. We have demonstrated that serotype A1, but not A2, M. haemolytica invades differentiated BBECs by transcytosis and subsequently undergoes rapid intracellular replication before spreading to adjacent cells and causing extensive cellular damage. Our findings suggest that the explosive proliferation of serotype A1 M. haemolytica that occurs within the bovine respiratory tract prior to the onset of pneumonic disease is potentially due to bacterial invasion of, and rapid proliferation within, the mucosal epithelium. The discovery of this previously unrecognised mechanism of pathogenesis is important because it will allow the serotype A1-specific virulence determinants responsible for invasion to be identified and thereby provide opportunities for the development of new strategies for combatting BRD aimed at preventing early colonisation and infection of the bovine respiratory tract

Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface

There is an urgent need to develop improved, physiologically-relevant in vitro models of airway epithelia with which to better understand the pathological processes associated with infection, allergies and toxicological insults of the respiratory tract of both humans and domesticated animals. In the present study, we have characterised the proliferation and differentiation of primary bovine bronchial epithelial cells (BBECs) grown at an air-liquid interface (ALI) at three-day intervals over a period of 42 days from the introduction of the ALI. The differentiated BBEC model was highly representative of the ex vivo epithelium from which the epithelial cells were derived; a columnar, pseudostratified epithelium that was highly reflective of native airway epithelium was formed which comprised ciliated, goblet and basal cells. The hallmark defences of the respiratory tract, namely barrier function and mucociliary clearance, were present, thus demonstrating that the model is an excellent mimic of bovine respiratory epithelium. The epithelium was fully differentiated by day 21 post-ALI and, crucially, remained healthy and stable for a further 21 days. Thus, the differentiated BBEC model has a three-week window which will allow wide-ranging and long-term experiments to be performed in the fields of infection, toxicology or general airway physiology

Development and optimization of a differentiated airway epithelial cell model of the bovine respiratory tract

Cattle are subject to economically-important respiratory tract infections by various bacterial and viral pathogens and there is an urgent need for the development of more realistic in vitro models of the bovine respiratory tract to improve our knowledge of disease pathogenesis. In the present study, we have optimized the culture conditions in serum-free medium that allow bovine bronchial epithelial cells (BBECs) grown at an air-liquid interface to differentiate into a three-dimensional epithelium that is highly representative of the bovine airway. Epidermal growth factor was required to trigger both proliferation and differentiation of BBECs whilst retinoic acid was also essential for mucociliary differentiation. Triiodothyronine was demonstrated not to be important for the differentiation of BBECs. Oxygen concentration had a minimal effect although optimal ciliation was achieved when BBECs were cultured at 14% oxygen tension. Insert pore-density had a significant effect on the growth and differentiation of BBECs; a high-pore-density was required to trigger optimum differentiation. The established BBEC model will have wide-ranging applications for the study of bacterial and viral infections of the bovine respiratory tract; it will contribute to the development of improved vaccines and therapeutics and will reduce the use of cattle in in vivo experimentation

Persistent holes in a fluid

We observe stable holes in a vertically oscillated 0.5 cm deep aqueous suspension of cornstarch for accelerations a above 10g. Holes appear only if a finite perturbation is applied to the layer. Holes are circular and approximately 0.5 cm wide, and can persist for more than 10^5 cycles. Above a = 17g the rim of the hole becomes unstable producing finger-like protrusions or hole division. At higher acceleration, the hole delocalizes, growing to cover the entire surface with erratic undulations. We find similar behavior in an aqueous suspension of glass microspheres.Comment: 4 pages, 6 figure

Subjective Cognitive Decline Higher Among Sexual and Gender Minorities in the United States, 2015–2018

Introduction: Subjective cognitive decline (SCD) represents self-reported problems with memory, a possible early sign of dementia. Little is known about SCD among sexual and gender minority (SGM) adults who identify as lesbian, gay, bisexual, and/or transgender or gender non-binary. Methods: Data were weighted to represent population estimates from 25 states’ 2015–2018 Behavioral Risk Factor Surveillance System to describe SCD in adults ≥ 45 years by SGM status. Logistic regression tested associations between demographic and health conditions. Results: SCD prevalence was higher in SGM (15.7%; 95% confidence interval [CI]:13.1–18.2) than in non-SGM adults (10.5%; 95% CI:10.1–10.9; P \u3c .0001). SGM adults with SCD were also more likely to report functional limitations due to SCD than non-SGM adults with SCD, 60.8% versus 47.8%, P =.0048. Differences in SCD by SGM status were attenuated after accounting for depression. Discussion: Higher prevalence of SCD in SGM adults highlights the importance of ensuring inclusive screenings, interventions, care services, and resources for SGM adults

Exploring social media recruitment strategies and preliminary acceptability of an mHealth tool for teens with eating disorders

(1) Background: The current study leveraged social media to connect with teens with EDs to identify population specific characteristics and to gather feedback on an mHealth intervention. (2) Methods: We recruited teens with EDs from social media in two phases: (1) Discovery Group, (2) Testing Group. The Discovery Group

Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD

Exile Vol. XLIII No. 2

41st Year Title Page i Epigraphy by Ezra Pound ii Table of Contents iii / Contributors\u27 Notes 70-71 Editorial Board 72-73 ART Untitled by Kari Hernquist \u2799 4 Talking Out my Window by Heather Trabert \u2797 13 Renamed I by Ben Blake \u2797 18 photo paint by alex e. blazer \u2797 23 Butterfly by Mary Donnelley \u2797 32 unabridged by alex e. blazer \u2797 37 Holding Me In by Heather Trabert \u2797 43 Untitled by Kari Hernquist \u2797 55 Untitled by Camille Gammon-Hittelman \u2799 61 Stars by Mary Donnelley \u2797 69 POETRY Victrola by erin c. malone \u2799 1 All by Kellam Ayres \u2797 2-3 curtailed sun in the net by alex e. blazer \u2797 5 the weaker sex by Bekah Taylor \u2700 6 A poem concerning a silent manifesto by Colin Bossen \u2798 14 Father by Alison Stine \u2700 15 Vacant by Sean Boyle \u2700 16 Ecstasy by Amy spears \u2798 17 Seven Haikus by Jen Suster \u2797 21 Pages from a Diary by Trish Klei \u2797 22 Watching an Ageless Woman and an Ancient Trade by Heather Trabert \u2797 24-25 Still Waters by Jay Brandeis \u2799 26 just shy of freedom by Sean Boyle \u2700 36 [Touch the mothers you never knew] by Heather Trabert \u2797 38 Fishing for Meaning by Bekah Taylor \u2700 39 the novel by Sara Brown \u2799 40-41 annihilation by erin c. malone \u2799 42 Upon Enlistment by Trish Klei \u2797 44 the expatriate by erin c. malone \u2799 47 Rockettes by Trish Klei \u2797 48-49 Abstraction by Colin Bossen \u2798 54 always kinesis by alex e. blazer \u2797 56-57 Lily by Alison Stine \u2700 58-59 Falling In by Bekah Taylor \u2700 60 this bird has flown by paul durica \u2700 62-63 exfoliating some sun by alex e. blazer \u2797 64 Liberation: May 8, 1945 by Jen suster \u2797 65 PROSE Journal: 12 December 1996 through 15 January 1997 by Lynn Tramonte \u2798 7-12 Ash by paul durica \u2700 19-20 Birdhouse by Tyler Smith \u2797 27-35 Party in December by paul durica \u2700 45-46 Smoke Circles by Alison Stine \u2700 50-53 Seal by Lynn Tramonte \u2798 66-68 All submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. -72 Cover art Toy Child by Ben Blake \u2797 -7

The Project ENABLE Cornerstone Randomized Controlled Trial: Study Protocol for a Lay Navigator-led, Early Palliative Care Coaching Intervention for African American and Rural-dwelling Advanced Cancer Family Caregivers

Background: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer.Methods: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin’s Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20–60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient’s death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient’s death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated.Discussion: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances