Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma.

Background: Airway tissue eosinophilia can be an observed feature of obesity-associated type 2 (T2) asthma, but the processes mediating this inflammation are unknown.

Objective: To investigate a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma.

Methods: We assessed associations between body mass index and airway eosinophilia as well as leptin and eotaxin production in 78 participants with asthma, 36 of whom exhibited obesity.

Withaferin A reduces pulmonary eosinophilia and IL-25 production in a mouse model of allergic airways disease.

Several studies report that ashwagandha, a traditional Ayurvedic supplement, has anti-inflammatory properties. Type 2 (T2) asthma is characterized by eosinophilic airway inflammation. We hypothesized that allergen-induced eosinophilic airway inflammation in mice would be reduced following administration of Withaferin A (WFA), the primary active phytochemical in Ashwagandha.

Revealing the extent of sea otter impacts on bivalve prey through multi-trophic monitoring and mechanistic models.

Sea otters are apex predators that can exert considerable influence over the nearshore communities they occupy. Since facing near extinction in the early 1900s, sea otters are making a remarkable recovery in Southeast Alaska, particularly in Glacier Bay, the largest protected tidewater glacier fjord in the world. The expansion of sea otters across Glacier Bay offers both a challenge to monitoring and stewardship and an unprecedented opportunity to study the top-down effect of a novel apex predator across a diverse and productive ecosystem.

Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity.

Introduction: Asthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization.

Recursive Bayesian computation facilitates adaptive optimal design in ecological studies.

Optimal design procedures provide a framework to leverage the learning generated by ecological models to flexibly and efficiently deploy future monitoring efforts. At the same time, Bayesian hierarchical models have become widespread in ecology and offer a rich set of tools for ecological learning and inference. However, coupling these methods with an optimal design framework can become computationally intractable.

Imbalanced Coagulation in the Airway of Type-2 High Asthma with Comorbid Obesity.

Asthma is a common, chronic airway inflammatory disease marked by airway hyperresponsiveness, inflammation, and remodeling. Asthma incidence has increased rapidly in the past few decades and recent multicenter analyses have revealed several unique asthma endotypes. Of these, type-2 high asthma with comorbid obesity presents a unique clinical challenge marked by increased resistance to standard therapies and exacerbated disease development.

Diffusion modeling reveals effects of multiple release sites and human activity on a recolonizing apex predator.

Background: Reintroducing predators is a promising conservation tool to help remedy human-caused ecosystem changes. However, the growth and spread of a reintroduced population is a spatiotemporal process that is driven by a suite of factors, such as habitat change, human activity, and prey availability. Sea otters (Enhydra lutris) are apex predators of nearshore marine ecosystems that had declined nearly to extinction across much of their range by the early 20th century.

Monitoring dynamic spatio-temporal ecological processes optimally.

Population dynamics vary in space and time. Survey designs that ignore these dynamics may be inefficient and fail to capture essential spatio-temporal variability of a process. Alternatively, dynamic survey designs explicitly incorporate knowledge of ecological processes, the associated uncertainty in those processes, and can be optimized with respect to monitoring objectives.

Source levels and call parameters of harbor seal breeding vocalizations near a terrestrial haulout site in Glacier Bay National Park and Preserve.

Source levels of harbor seal breeding vocalizations were estimated using a three-element planar hydrophone array near the Beardslee Islands in Glacier Bay National Park and Preserve, Alaska. The average source level for these calls was 144 dB re 1 μPa at 1 m in the 40-500 Hz frequency band. Source level estimates ranged from 129 to 149 dB re 1 μPa.

An integrated data model to estimate spatiotemporal occupancy, abundance, and colonization dynamics.

Ecological invasions and colonizations occur dynamically through space and time. Estimating the distribution and abundance of colonizing species is critical for efficient management or conservation. We describe a statistical framework for simultaneously estimating spatiotemporal occupancy and abundance dynamics of a colonizing species.

Quantification and Analysis of Icebergs in a Tidewater Glacier Fjord Using an Object-Based Approach.

Tidewater glaciers are glaciers that terminate in, and calve icebergs into, the ocean. In addition to the influence that tidewater glaciers have on physical and chemical oceanography, floating icebergs serve as habitat for marine animals such as harbor seals (Phoca vitulina richardii). The availability and spatial distribution of glacier ice in the fjords is likely a key environmental variable that influences the abundance and distribution of selected marine mammals; however, the amount of ice and the fine-scale characteristics of ice in fjords have not been systematically quantified.

Key Questions in Marine Megafauna Movement Ecology.

It is a golden age for animal movement studies and so an opportune time to assess priorities for future work. We assembled 40 experts to identify key questions in this field, focussing on marine megafauna, which include a broad range of birds, mammals, reptiles, and fish. Research on these taxa has both underpinned many of the recent technical developments and led to fundamental discoveries in the field.

Post-breeding season migrations of a top predator, the harbor seal (Phoca vitulina richardii), from a marine protected area in Alaska.

Marine protected areas (MPAs) are increasingly being used as a conservation tool for highly mobile marine vertebrates and the focus is typically on protecting breeding areas where individuals are aggregated seasonally. Yet movements during the non-breeding season can overlap with threats that may be equally as important to population dynamics. Thus understanding habitat use and movements of species during the non-breeding periods is critical for conservation.

Segmental pulmonary resection for cancer.

Segmental pulmonary resection was employed in 61 patients with cancer whose ages ranged from 44 to 82 years (average 62 years). There were 39 patients in the curative group with disease staged T1N0M0, 9 patients in the limited group with residual thoracic disease, 8 patients in the palliative group with severe chronic obstructive pulmonary disease, and 5 patients in the metastatic group. Two patients died within 30 days after operation.

Urinary polyamine levels are markers of altered T lymphocyte proliferation/loss and rejection in heart transplant patients.

The studies of urinary polyamine excretion in heart transplant patients reported in this article indicate that (1) total urinary polyamine excretion is increased one to three days before a biopsy-proved rejection in conventionally treated patients, (2) the acetylputrescine to N1-acetylspermidine ratio becomes elevated before rejection in cyclosporine-treated patients, and (3) the response to elevated ATG therapy during rejection can be evaluated by monitoring urinary polyamine concentrations. We conclude that daily monitoring of urinary polyamine levels may provide a noninvasive biochemical marker that precedes rejection and which parallels the extent of T lymphocyte suppression during the course of immunosuppressive drug therapy.

Doxepin's effects on chronic pain and depression: a controlled study.

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml.

Concurrent left and right ventricular hypertrophy in dog models of right ventricular overload.

In two pressure and volume overload models of canine right ventricular hypertrophy, we have demonstrated significant hypertrophy of both the left and the right ventricles. The extent of hypertrophy was correlated positively to the extent of the increase in plasma epinephrine in both volume and pressure overload models. Attenuation or ablation of plasma epinephrine through the administration of propranolol, a beta-adrenergic blocker, or by denervation of the adrenal medulla prevented the hypertrophy process.

A model of delayed aortic coarctation employing arterial and venous catheters for chronic blood sampling in conscious dogs.

We have developed a reproducible model of cardiac hypertrophy in conscious, unrestrained dogs after recovery from surgical trauma. The model has many potential applications due to the availability of non-stressful blood sampling from four arterial and/or venous vascular locations. Samples of blood for biochemical or pharmacological measurements were obtained from the carotid and femoral arteries as well as the pulmonary artery and inferior vena cava.

Doxepin effects on chronic pain, depression and plasma opioids.

Thirty patients with chronic low back or cervical pain combined with clinical depression were studied in a six-week, randomized, double-blind comparison of doxepin and placebo. Dependent variables included Hamilton Depression Scores, the Clinical Global Assessment Scale, and Profile of Mood States (POMS), and subjective ratings (visual analogue scales) of pain severity, percent of time pain felt, and effect of pain on activity, muscle tension, sleep, mood, and analgesic drug consumption. Plasma levels of doxepin, desmethyldoxepin, beta-endorphin, and enkephalin-like activity were also measured.

Transglutaminase may mediate certain physiological effects of endogenous amines and of amine-containing therapeutical agents.

Transglutaminase mediation of the effects of certain primary amines and alcohols may be important in receptor coupling to physiological responses. Many of the therapeutic and toxic side effects of drugs also may be related to their covalent linkage of glutamine residues of key regulatory proteins through the catalytic action of transglutaminase. This paper suggests that important therapeutic agents such as digoxin, tetracycline, adriamycin, and actinomycin D may have some effects related to transglutaminase action.

beta 2-Adrenoceptors regulate induction of myocardial ornithine decarboxylase in mice in vivo.

The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.

Comparison of bupivacaine, etidocaine, and saline for trigger-point therapy.

Injections of local anesthetics, saline, "dry needling," or other stimuli at specific, tender loci (trigger or acupuncture points) are reportedly efficacious in treatment of chronic pain syndromes. In a randomized, double-blind crossover study, subjective responses of 15 patients with myofascial syndrome to trigger-point injections of either bupivacaine 0.5%, etidocaine 1%, or physiologic saline without preservative were compared.