Chemoreceptor responsiveness at sea level does not predict the pulmonary pressure response to high altitude

The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA. In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2 -1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21). Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07). We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA

K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

<p>Abstract</p> <p>Background</p> <p>Lung epithelial Na⁺channels (ENaC) are regulated by cell Ca²⁺signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K⁺channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K⁺channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport.</p> <p>Methods</p> <p>Verapamil-induced depression of heterologously expressed human αβγ ENaC in <it>Xenopus </it>oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and <it>in vivo </it>alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca²⁺signal in H441 cells was analyzed using Fluo 4AM.</p> <p>Results</p> <p>The rate of <it>in vivo </it>AFC was reduced significantly (40.6 ± 6.3% of control, <it>P </it>< 0.05, n = 12) in mice intratracheally administrated verapamil. K_Ca3.1(1-EBIO) and K_ATP(minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca²⁺signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca²⁺in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, K_V(pyrithione-Na), K _Ca3.1(1-EBIO), and K_ATP(minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na⁺and K⁺transport pathways.</p> <p>Conclusions</p> <p>Our observations demonstrate that K⁺channel openers are capable of rescuing reduced vectorial Na⁺transport across lung epithelial cells with impaired Ca²⁺signal.</p

Climate warriors down under: Contextualising Australia’s youth climate justice movement

Abstract This perspective brings together published peer reviewed primary research on youth climate activism in Australia and provides context of the political and social landscapes in which young people are taking climate action. As the generation most vulnerable to the impacts of climate change, young people all over the world have mobilised to drive a climate justice narrative to the fore of the climate movement. Climate justice framing will be applied to contextualise youth climate activism in Australia. This perspective also addresses the context-specific challenges faced by youth, including the media’s role in shaping public perceptions and, anti-protest laws that restrict the right to protest. Finally, this perspective highlights the opportunities for how to support youth climate activism in the future

The 'Toolbox' of strategies for managing Haemonchus contortus in goats: what's in and what's out

A dynamic and innovative approach to managing the blood-consuming nematode Haemonchus contortus in goats is critical to crack dependence on veterinary anthelmintics. H. contortus management strategies have been the subject of intense research for decades, and must be selected to create a tailored, individualized program for goat farms. Through the selection and combination of strategies from the Toolbox, an effective management program for H. contortus can be designed according to the unique conditions of each particular farm. This Toolbox investigates strategies including vaccines, bioactive forages, pasture/grazing management, behavioural management, natural immunity, FAMACHA, Refugia and strategic drenching, mineral/vitamin supplementation, copper Oxide Wire Particles (COWPs), breeding and selection/selecting resistant and resilient individuals, biological control and anthelmintic drugs. Barbervax(®), the ground-breaking Haemonchus vaccine developed and currently commercially available on a pilot scale for sheep, is prime for trialling in goats and would be an invaluable inclusion to this Toolbox. The specialised behaviours of goats, specifically their preferences to browse a variety of plants and accompanying physiological adaptations to the consumption of secondary compounds contained in browse, have long been unappreciated and thus overlooked as a valuable, sustainable strategy for Haemonchus management. These strategies are discussed in this review as to their value for inclusion into the 'Toolbox' currently, and the future implications of ongoing research for goat producers. Combining and manipulating strategies such as browsing behaviour, pasture management, bioactive forages and identifying and treating individual animals for haemonchosis, in addition to continuous evaluation of strategy effectiveness, is conducted using a model farm scenario. Selecting strategies from the Toolbox, with regard to their current availability, feasibility, economical cost and potential ease of implementation depending on the systems of production and their complementary nature, is the future of managing H. contortus in farmed goats internationally and maintaining the remaining efficacy of veterinary anthelmintics