Effects of Inhaled Brevetoxins in Allergic Airways: Toxin–Allergen Interactions and Pharmacologic Intervention

During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma). To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (R(L)) after inhalation challenge with lysed cultures of K. brevis (crude brevetoxins). Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 pg/mL; n = 5) increased R (L) 128 ± 6% (mean ± SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the β (2) adrenergic agent albuterol (71%), the anticholinergic agent atropine (58%), and the histamine H(1)-antagonist diphenhydramine (47%). The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and H(1)-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals

The Mare Reproductive Loss Syndrome and the Eastern Tent Caterpillar II: A Toxicokinetic/Clinical Evaluation and a Proposed Pathogenesis: Septic Penetrating Setae

Reviewing the mare reproductive loss syndrome (MRLS), it is proposed that the fundamental mechanism of this syndrome, which includes early fetal loss, late fetal loss, uveitis, pericarditis, and encephalitis, is tissue penetration by septic barbed setal fragments (septic penetrating setae) from Eastern tent caterpillars (Malacosoma americanum). Once ingested, these barbed setal fragments migrate through moving tissues, followed by rapid hematogenous spread of bacteria, bacterial emboli, and/or septic fragments of setae (septic penetrating setal emboli), collectively referred to as septic materials. Pathogenic bacteria, therefore, enter the horse as hitchhikers on or in the caterpillar setal fragments, and MRLS is caused by 1) the barbed setal fragments’ ability to penetrate moving tissues, including blood vessels, releasing septic materials, which rapidly distribute hematogenously; 2) the high sensitivity of the pregnant mare to bacteria from such septic materials introduced into the uterus, fetal membranes, or fetal fluids; 3) the unusually broad spectrum of bacterial pathogens carried on or in the setal fragments; and 4) the less effective antibacterial responses in certain susceptible extracellular fluids (e.g., fetal, ocular, pericardial, and cerebrospinal fluids). The driving force for MRLS pathology, including abortions, is septic material- induced bacterial proliferation, which provides a critical amplification step, enabling approximately 1-gram caterpillars to rapidly (32 hours) cause abortions in 680-kg (1,500- lb) mares. Calculations based on the unique eye data suggest that the actual number of distributing effective septic material quanta in field cases may be small—on the order of 10/horse/day—accounting for the lack of systemic clinical signs in affected horses. Therefore, it is proposed that MRLS starts with ingestion of Eastern tent caterpillars, followed by barbed setal fragments randomly penetrating intestinal tissues, including thinwalled venules and other blood vessels, with release of septic material that distributes hematogenously to all points in the body. Identification of abortigenic activity with the integument of the caterpillar and recent findings of large numbers of granulomatous lesions containing setal fragments in the intestines of pigs and rats directly supports the septic penetrating setal portion of the hypothesis. Analysis of the clinical syndromes and a toxicokinetic/ statistical analysis of MRLS suggest that setally-mediated introduction of septic material into blood vessels and other tissues may be key to understanding the very unusual toxicokinetics and pathogenesis of the unique group of syndromes that constitute MRLS. Like MRLS itself, this hypothesis is unique. The septic penetrating setal emboli portion is without precedent, is based on the unique clinical characteristics of MRLS, and appears well supported by ongoing experimental approaches

Hydrology of the Ferron Sandstone Aquifer and Effects of Proposed Surface-Coal Mining in Castle Valley, Utah

Coal in the Ferron Sandstone Member of the Mancos Shale of Cretaceous age has traditionally been mined by underground techniques in the Emery Coal Field in the southern end of Castle Valley in east-central Utah. However, approximately 99 million tons are recoverable by surface mining. Ground water in the Ferron is the sole source of supply for the town of Emery, but the aquifer is essentially untapped outside the Emery area. The Ferron Sandstone Member crops out along the eastern edge of Castle Valley and generally dips 2 to 10 to the northwest beneath the surface. Sandstones in the Ferron are enclosed between relatively impermeable shale in the Tununk and Blue Gate Members of the Mancos Shale. Along the outcrop, the Ferron ranges in thickness from about 80 feet in the northern part of Castle Valley to 850 feet in the southern part. The Ferron also generally thickens in the subsurface downdip from the outcrop. Records from wells and test holes indicate that the full thickness of the Ferron is saturated with water in most areas downdip from the outcrop area. Tests in the Emery area indicate that transmissivity of the Ferron sandstone aquifer ranges from about 200 to 700 feet squared per day where the Ferron is fully saturated. Aquifer transmissivity is greatest near the Paradise Valley-- Joes Valley fault system where permeability has been increased by fracturing. Storage coefficient ranges from about 10^-6 to 10^-3 where the Ferron sandstone aquifer is confined and probably averages 5 x 10^-2 where in is unconfined

THE SYMMETRY ANGLE IDENTIFIES LESS CLINICALLY RELEVANT INTER-LIMB ASYMMETRIES THAN THE SYMMETRY INDEX IN HEALTHY ADULTS

There are several methods for calculating inter-limb symmetry, an inter-limb difference ≥15% has been suggested as an indicator of sporting injury risk. The purpose of this study was to compare three common methods for determining symmetry: the Symmetry Index (percentage difference; SI) when referenced to the left limb (SILeft) or the average of both limbs (SIAverage), and the Symmetry Angle (vector difference; SA). 15 recreationally active participants completed a sprint protocol on a non-motorised treadmill. Accelerometers were positioned on both tibias to measure peak resultant acceleration (PRA). The SA identified less clinically relevant PRA inter-limb asymmetries than the SI in healthy adults. Once an appropriate level of asymmetry as measured by the SA is determined, this may help to more correctly identify asymmetry in athletes and patients than the SI

Future Directions for Whole Atmosphere Modeling:Developments in the Context of Space Weather

Coupled Sun‐to‐Earth models represent a key part of the future development of space weather forecasting. With respect to predicting the state of the thermosphere and ionosphere, there has been a recent paradigm shift; it is now clear that any self‐respecting model of this region needs to include some representation of forcing from the lower atmosphere, as well as solar and geomagnetic forcing. Here we assess existing modeling capability and set out a roadmap for the important next steps needed to ensure further advances. These steps include a model verification strategy, analysis of the impact of non‐hydrostatic dynamical cores, and a cost‐benefit analysis of model chemistry for weather and climate applications