Lipid-laden alveolar macrophages and pH monitoring in gastroesophageal reflux-related respiratory symptoms

Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER). This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL). Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed

THE MACROSCOPIC, HISTOLOGIC, AND IMMUNOMODULATORY EFFECTS OF INTRAVENOUS ALLOGENEIC EQUINE UMBILICAL CORD BLOOD-DERIVED MULTIPOTENT MESENCHYMAL STROMAL CELL THERAPY ON EXPERIMENTALLY CREATED LIMB WOUNDS IN THE HORSE

BACKGROUND: Limb wound on horses are often slow to heal and are prone to developing exuberant granulation tissue (EGT) and close primarily through epithelialization, which results in a cosmetically inferior and less durable repair. In contrast, wounds on the body heal rapidly and primarily through contraction and rarely develop EGT. Intravenous (IV) multipotent mesenchymal stromal cells (MSCs) are promising. They home and engraft to cutaneous wounds and promote healing in laboratory animals, but this had not been demonstrated in the horse. Furthermore, the clinical safety of administering >1.00 x 108 allogeneic (allo) MSCs IV to a horse has not been determined. PILOT PROJECT: A proof-of-principle pilot project was performed with two horses that were administered 1.02 x 108 fluorescently labelled allo-cord blood-derived MSCs (CB-MSCs) following surgical wound creation on the forelimb and thorax. Results confirmed preferential homing and engraftment to wounds with persistence of CB-MSCs at 33 days following wound creation, without clinically adverse reactions to the infusion. SECONDARY PROJECT: A minor secondary project was developed from the pilot project, where the mRNA of the inflammation-associated proteins β-arrestin-2 (βarr2), CXC ligand (CXCL) 8, CXC receptor (CXCR) 2, CXCL10, and CXCR3 was compared in limb and thoracic wounds. Results suggest that there are differences in expression between βarr2 and CXCL8/CXCR2 in limb and thoracic wounds. MAJOR PROJECT: Materials and Methods: Wound were surgically created on the forelimbs of treatment and control horses. 1.51 – 2.46 x 108 allo-CB-MSCs were administered to treatment horses 12 hours after wound creation and were monitored for clinically adverse reactions during infusion. Control horses were administered diluted cellular suspension medium (HTS-FRS) only. Biopsies of the wounds were collected on days 0, 1, 2, 7, 14, and 28 from treatment and control horses. The biopsies tissue was dived – a portion was snap frozen and analyzed using multiplex mRNA assays for proinflammatory (TNFα, CXCL8), anti-inflammatory (IL-4, IL-8), inflammation resolving INFγ, CXCL10), profibrotic (TGFβ1, TGFβ2), and anti-fibrotic (TGFβ3) cytokines, and the other portion was evaluated histologically and given a combined repair and inflammation score. The wounds were photographed on days 7, 14, and 28 and evaluated for wound size and total percentage of wound closure by contraction and epithelialization using planimetric analysis. Day of wound closure was recorded when the granulation tissue was covered with epithelium. Rate of wound closure, percentage of contraction, percentage of epithelialization, and mean fold change of cytokines was evaluated using generalized estimating equations for an overall treatment effect over all days (P≤0.2) and pairwise comparison for treatment effect at individual days (P≤0.05). Results: 3/6 (50%) treatment horses and 1/6 (17%) control horses experiences clinically adverse responses during injection. Day to wound closure was not significantly improved (treatment 26+/- 4 days, control 27 +/- 3 days; two sample T-test, P=0.702), although overall wound size (GEE; P=0.145) was decreased, characterized by overall increased contraction (GEE; P=0.145) and decreased epithelization (GEE: P=0.015) with significantly less epithelization on day 14 (GEE, PWC; P=0.0173). Histologic repair score was not improved and virtually identical between groups, thus no static analysis was performed. There was overall decrease in proinflammatory (GEE; P=0.032), anti-inflammatory (GEE; P=0.022), inflammation resolving (GEE; P=0.033) and profibrotic (GEE; P=0.191) cytokines with significantly less proinflammatory cytokines on day 2 (GEE; P=0.0003). There was no difference in antifibrotic cytokines. CONCLUSIONS: Administered >1.51 x 108 IV allo-CB-MSCs suspended in HTS-FRS can induce infusion reactions in recipients which may be caused by antigenic stimulation or the suspension medium. IV allo-CB-MSC therapy did not improve time to wound closure or histologic repair scores, although overall wound size was smaller due to increased contraction and decreased epithelization. IV allo-CB-MSCs decreased expression of all cytokines except for antifibrotic cytokines. Although minor improvements in wound healing were measured, the advantages of IV allo-CB-MSC therapy likely do not justify the risks of infusion reactions. Investigation into other methods of MSC delivery and therapies are warranted

The delivery of bad news:An integrative review and path forward

Managing the delivery of bad news is a crucial component of effective human resource management. However, the diversity of contexts in which this phenomenon has been studied has made it difficult to develop a consolidated theoretical and practical understanding of bad news delivery. Using an interdisciplinary integrative review (N = 685), we critically analyze how bad news delivery has been conceptualized as well as what interdisciplinary theoretical insights and practical guidance can be offered. Beyond identifying key challenges in the extant literature, we also provide a path forward by showcasing key opportunities, including how conceptualizing bad news delivery as a dialectic process that unfolds over time can further enhance theoretical insights and practical guidance for effectively managing bad news delivery in the workplace

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch((R)) and Parsortix platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside

Technical note: Novel estimates of the leaf relative uptake rate of carbonyl sulfide from optimality theory

In order to estimate the gross primary productivity (GPP) of terrestrial ecosystems from the canopy uptake of carbonyl sulfide (COS), the leaf relative uptake rate (LRU) of COS with respect to carbon dioxide needs to be known a priori. Currently, the variability of the LRU between plant species in different biomes of the world is poorly understood, making the choice of an appropriate LRU uncertain and hampering further progress towards developing COS as an alternative tracer of GPP. Here we propose a novel approach for estimating LRU based on plant optimality principles, validate it against in situ leaf gas exchange measurements and provide global monthly climatological estimates. The global vegetation season average simulated LRUs fall into the range of 0.5&ndash;1.4 and are thus lower than any other published global estimates. We advocate these LRU estimates to be adopted by global modellers in order to test to what degree these are compatible with our current understanding of the sources and sinks in the global COS budget.</p

Nematode-Destroying Fungi of Johnson County, Iowa

The nematode-destroying fungi in woodland areas of Johnson County, Iowa were surveyed. Twenty-six species of predacious fungi were identified, including 5 species newly reported for Iowa: Arthrobotrys superba Corda, Cephalosporium balanoides Drech., Dactylella asthenopaga Drech., Harposporium bysmatosporum Drech., and H. subuliforme Drech. A fungus similar to Nematoctonus pachysporus Drech., but lacking clamp connections, is discussed