Retrospective computed tomography analysis of endotracheal tube constriction and mispositioning in cats and dogs.

OBJECTIVE: To discover the prevalence of endotracheal tube (ETT) constriction and rostral and caudal mispositioning in anaesthetized cats and dogs, and to identify associated risk factors. STUDY DESIGN: Retrospective analysis. ANIMALS: A total of 146 cats and 670 dogs. METHODS: Computed tomography images of the head/neck/thorax from orotracheally intubated cats and dogs were visually assessed for constriction or mispositioning of the ETT. If constriction was present, measurements of the cross-sectional area (CSA) of the ETT lumen at constricted and un-constricted locations were compared. Location and cause of constriction were noted and the expected increase in resistance to gas flow was calculated. Animal information was collected from clinical records. Normality of continuous variables was assessed via the Shapiro-Wilk test. Chi-square tests examined associations between variables. Kendall's tau-b test was performed between measured ETT size and degree of constriction. RESULTS: The ETT extended rostrally beyond incisors in 52% of cases; the connector was within the oral cavity in 19% of cases. The ETT extended beyond the first rib in 25.5% of cases. The prevalence of ETT constriction was 22.7%. Median reduction in CSA was 7.68% (0.14-64.19%). Median increase in resistance assuming laminar and turbulent flow was 16.5% (0.3-680%) and 21% (0.3-1200%), respectively. The most common cause of constriction was the presence of a radiotherapy mouth gag. Significant associations existed between presence of constriction and rostral mispositioning, and caudal mispositioning and extreme brachycephaly. Increased severity of constriction was more likely in smaller ETT. CONCLUSIONS AND CLINICAL RELEVANCE: Constriction and mispositioning of ETT occurred very commonly in this population. Checking the ETT within the oral cavity for constriction and mispositioning is recommended. Radiotherapy mouth gags increase the risk of ETT compression. Smaller ETT are at greater risk of severe constriction. Brachycephalic dogs are at particular risk of caudal mispositioning.

Opioid suppression of conditioned anticipatory brain responses to breathlessness.

Opioid painkillers are a promising treatment for chronic breathlessness, but are associated with potentially fatal side effects. In the treatment of breathlessness, their mechanisms of action are unclear. A better understanding might help to identify safer alternatives. Learned associations between previously neutral stimuli (e.g. stairs) and repeated breathlessness induce an anticipatory threat response that may worsen breathlessness, contributing to the downward spiral of decline seen in clinical populations. As opioids are known to influence associative learning, we hypothesized that they may interfere with the brain processes underlying a conditioned anticipatory response to breathlessness in relevant brain areas, including the amygdala and the hippocampus. Healthy volunteers viewed visual cues (neutral stimuli) immediately before induction of experimental breathlessness with inspiratory resistive loading. Thus, an association was formed between the cue and breathlessness. Subsequently, this paradigm was repeated in two identical neuroimaging sessions with intravenous infusions of either low-dose remifentanil (0.7ng/ml target-controlled infusion) or saline (randomised). During saline infusion, breathlessness anticipation activated the right anterior insula and the adjacent operculum. Breathlessness was associated with activity in a network including the insula, operculum, dorsolateral prefrontal cortex, anterior cingulate cortex and the primary sensory and motor cortices. Remifentanil reduced breathlessness unpleasantness but not breathlessness intensity. Remifentanil depressed anticipatory activity in the amygdala and the hippocampus that correlated with reductions in breathlessness unpleasantness. During breathlessness, remifentanil decreased activity in the anterior insula, anterior cingulate cortex and sensory motor cortices. Remifentanil-induced reduction in breathlessness unpleasantness was associated with increased activity in the rostral anterior cingulate cortex and nucleus accumbens, components of the endogenous opioid system known to decrease the perception of aversive stimuli. These findings suggest that in addition to effects on brainstem respiratory control, opioids palliate breathlessness through an interplay of altered associative learning mechanisms. These mechanisms provide potential targets for novel ways to develop and assess treatments for chronic breathlessness.

The effect of acetazolamide on saccadic latency at 3459 meters.

OBJECTIVE: The effect of altitude on brain function is not yet well understood, nor is the influence of height and speed of ascent. Additionally, the relationship between acute mountain sickness (AMS) symptoms and brain function at altitude is unclear. We hypothesized that a deterioration from baseline measures of brain function occurs after rapid, mechanical ascent to 3459 m and would be less pronounced in persons taking acetazolamide. METHODS: In this double blind, randomized, placebo-controlled study, 20 healthy volunteers (14 men, 6 women; mean age [±SD] 43 ± 16 years) were alternately allocated to acetazolamide 250 mg or to placebo, taken every 12 hours commencing 3 days before ascent. Prosaccadic and antisaccadic eye movements, heart rate, arterial saturation, and Lake Louise AMS scores were assessed at sea level and 15 to 22 hours after ascent to 3459 m. RESULTS: Arterial oxygen saturation was significantly lower in the placebo group compared to the acetazolamide group at altitude (Wilcoxon signed-rank test, median [interquartile range]: acetazolamide vs placebo: 92% [5] vs 85% [5]; P = .007), with no differences in prosaccadic latency, heart rate, or Lake Louise score. No differences in saccadic latencies from baseline to altitude were observed in the placebo group, whereas prosaccadic latencies were significantly longer at altitude with acetazolamide (altitude vs baseline: 153 ms [41] vs 176 ms [52], P = .008). CONCLUSIONS: Brain function, measured by saccadic eye movements, appears to be unimpaired after rapid ascent to 3459 m. Although acetazolamide improves oxygen saturations, it may worsen prosaccades, possibly indicating adverse effects of acetazolamide on brain function at moderate altitude.

Digest: Plastic responses to warmer climates: a seminatural experiment on lizard populations.

Determining whether a phenotypic change is the result of microevolution or plasticity can be challenging. Bestion et al. investigate the contributions of plasticity (both intragenerational and intergenerational) and selection to phenotypic changes in common lizards (Zootoca vivipara) in response to a warmer climate that mirrors projections for 2080. Their results suggest that plasticity plays a more important role than selection in governing many of the phenotypic responses to temperature change.

A model framework for projecting the prevalence and impact of Long-COVID in the UK.

The objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 disease in the UK population, including symptoms of 'long-COVID'. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long-COVID. The prevalence of symptomatic COVID-19, encompassing acute symptoms and long-COVID symptoms, was modelled using a decay function. Permanent injury as a result of COVID-19 infection, was modelled as a fixed prevalence. Both parts were combined to calculate QALY loss due to COVID-19 symptoms. Assuming a 60% final attack rate for SARS-CoV-2 infection in the population, we modelled 299,730 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,764 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury). The UK Government willingness-to-pay to avoid these QALY losses would be £17.9 billion and £32.2 billion, respectively. Additionally, 90,143 people were subject to permanent injury from COVID-19 (0.14% of the population). Given the ongoing development in information in this area, we present a model framework for calculating the health economic impacts of symptoms following SARS-CoV-2 infection. This model framework can aid in quantifying the adverse health impact of COVID-19, long-COVID and permanent injury following COVID-19 in society and assist the proactive management of risk posed to health. Further research is needed using standardised measures of patient reported outcomes relevant to long-COVID and applied at a population level.

Evidence of a largely staminal origin for the Jaltomata calliantha (Solanaceae) floral corona.

BACKGROUND: Understanding the evolution of novel features requires homology assessments at different levels of biological organization. In flowering plants, floral coronas that play various roles in plant-pollinator interactions have evolved multiple times independently, but are highly variable in their final position and overall morphology. Coronas of the Solanaceae species Jaltomata calliantha are found between the corolla and stamens, adjacent to the gynoecium, and form cups that house copious amounts of their characteristic blood red nectar. To test the hypothesis that J. calliantha coronas evolved as an outgrowth of stamens and therefore have staminal identity, we assessed their development, floral organ identity gene expression, and cellular morphology. RESULTS: Jaltomata calliantha coronas emerge after the initiation of all conventional floral organs on the abaxial side of the proximally modified stamens and then expand medially and laterally to form nectar cups. Overlapping expression of the B-class organ identity genes JcAPETALA3 and both JcPISTILLATA/GLOBOSA orthologs (JcGLO1 and JcGLO2), and the C-class-like gene JcAGAMOUS1-like, unites the stamens and corona. Epidermal cell shape also connects the adaxial surface of coronas and petals, and the stamen base, with remaining floral organs showing divergent cell types. CONCLUSIONS: Our data, based on multiple lines of evidence, support a largely staminal origin for J. calliantha coronas. However, since slightly enlarged stamen bases are found in Jaltomata species that lack coronas, and J. calliantha stamen bases share cell types with petals, we hypothesize that stamen bases recruited part of the petal identity program prior to fully expanding into a corona.