Strategies to combat chronic critical illness

The population of chronically critically ill patients is growing as advances in intensive care management improve survival from the acute phase of critical illness. These patients are characterized by complex medical needs and heavy resource utilization. This article reviews evidence supporting a comprehensive approach to the prevention and management of chronic critical illness (CCI)

Sharing success - understanding barriers and enablers to secondary prophylaxis delivery for rheumatic fever and rheumatic heart disease

Background: Rheumatic fever (RF) and rheumatic heart disease (RHD) cause considerable morbidity and mortality amongst Australian Aboriginal and Torres Strait Islander populations. Secondary antibiotic prophylaxis in the form of 4-weekly benzathine penicillin injections is the mainstay of control programs. Evidence suggests, however, that delivery rates of such prophylaxis are poor. Methods: This qualitative study used semi-structured interviews with patients, parents/care givers and health professionals, to explore the enablers of and barriers to the uptake of secondary prophylaxis. Data from participant interviews (with 11 patients/carers and 11 health practitioners) conducted in four far north Queensland sites were analyzed using the method of constant comparative analysis. Results: Deficits in registration and recall systems and pain attributed to injections were identified as barriers to secondary prophylaxis uptake. There were also varying perceptions regarding responsibility for ensuring injection delivery. Enablers of secondary prophylaxis uptake included positive patient-healthcare provider relationships, supporting patient autonomy, education of patients, care givers and healthcare providers, and community-based service delivery. Conclusion: The study findings provide insights that may facilitate enhancement of secondary prophylaxis delivery systems and thereby improve uptake of secondary prophylaxis for RF/RHD

Changes in mixed microbial inoculums to prevent the toxic side-effects in cattle grazing new varieties of Leucaena.

Leucaena leucocephala is a legume fodder crop that grows in tropical and subtropical environments. Leucaena provides a high quality feed for cattle boosting liveweight gain both per animal and per hectare, improving profitability for steer turnover by 121% compared with the base scenario of grazing buffel grass (Bowen and Chudleigh, 2018). A number of commercial leucaena cultivars, Cunningham, Peru, Taramba, El Salvadore, and Wondergraze, are used in Queensland. Leucaena contains a toxic amino acid, mimosine, which many rumen bacteria can degrade to a toxic metabolite 3-hydroxy-4-(1H)-pyridone (DHP). Productivity from leucaena-pasture can be reduced by DHP-induced depressions in intake. A DHP degrading bacterium, Synergistes jonesii was isolated from a mixed bacterial population isolated from a goat from Hawaii (Allison et al., 1992). For over twenty years DAF has provided a mixed bacterial rumen inoculum, containing S. jonesii, for cattle grazing Leucaenapastures, produced in an in vitro fermentation system with Cunningham cultivar as the feed source. All of the commercial cultivars are susceptible to attack by psyllid insects, limiting their use in higher rainfall areas - to address this limitation, a commercial psyllid-resistant cultivar, Redlands, was released in 2019. To assess if the leucaena inoculum is impacted by Redland’s anti-psyllid, chemical characteristics a series of 30 day in vitro anaerobic fermentations were undertaken feeding either Redlands, Cunningham or Wondergraze cultivars. The fermentations were conducted following the method of Klieve et al. (2002). Fermentations were started with either cryopreserved leuceana inoculum from a single day of a production fermentation; or day 30 of a Wondergraze or Redlands fermentation. Daily samples were taken and assays set up on days 10, 15, 20, 25 and 30 to monitor the fermentation’s ability to break down mimosine, 3,4 DHP and 2,3 DHP. Genomic DNA extracted from daily samples was used in a S. jonesii quantitative PCR and for barcoded amplicon sequencing of the 16S rRNA gene V3 –V4 region using the Illumina MiSeq platform

Screen Use and Mental Health Symptoms in Canadian Children and Youth during the COVID-19 Pandemic

Importance: Longitudinal research on specific forms of electronic screen use and mental health symptoms in children and youth during COVID-19 is minimal. Understanding the association may help develop policies and interventions targeting specific screen activities to promote healthful screen use and mental health in children and youth. Objective: To determine whether specific forms of screen use (television [TV] or digital media, video games, electronic learning, and video-chatting time) were associated with symptoms of depression, anxiety, conduct problems, irritability, hyperactivity, and inattention in children and youth during COVID-19. Design, Setting, and Participants: A longitudinal cohort study with repeated measures of exposures and outcomes was conducted in children and youth aged 2 to 18 years in Ontario, Canada, between May 2020 and April 2021 across 4 cohorts of children or youth: 2 community cohorts and 2 clinically referred cohorts. Parents were asked to complete repeated questionnaires about their children\u27s health behaviors and mental health symptoms during COVID-19. Main Outcomes and Measures: The exposure variables were children\u27s daily TV or digital media time, video game time, electronic-learning time, and video-chatting time. The mental health outcomes were parent-reported symptoms of child depression, anxiety, conduct problems and irritability, and hyperactivity/inattention using validated standardized tools. Results: This study included 2026 children with 6648 observations. In younger children (mean [SD] age, 5.9 [2.5] years; 275 male participants [51.7%]), higher TV or digital media time was associated with higher levels of conduct problems (age 2-4 years: β, 0.22 [95% CI, 0.10-0.35]; P \u3c.001; age ≥4 years: β, 0.07 [95% CI, 0.02-0.11]; P =.007) and hyperactivity/inattention (β, 0.07 [95% CI, 0.006-0.14]; P =.04). In older children and youth (mean [SD] age, 11.3 [3.3] years; 844 male participants [56.5%]), higher levels of TV or digital media time were associated with higher levels of depression, anxiety, and inattention; higher levels of video game time were associated with higher levels of depression, irritability, inattention, and hyperactivity. Higher levels of electronic learning time were associated with higher levels of depression and anxiety. Conclusions and Relevance: In this cohort study, higher levels of screen use were associated poor mental health of children and youth during the COVID-19 pandemic. These findings suggest that policy intervention as well as evidence-informed social supports are needed to promote healthful screen use and mental health in children and youth during the pandemic and beyond

PTF11iqb: Cool supergiant mass loss that bridges the gap between Type IIn and normal supernovae

PTF11iqb was initially classified as a TypeIIn event caught very early after explosion. It showed narrow Wolf-Rayet (WR) spectral features on day 2, but the narrow emission weakened quickly and the spectrum morphed to resemble those of Types II-L and II-P. At late times, Halpha emission exhibited a complex, multipeaked profile reminiscent of SN1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN~1998S, although with weaker interaction with circumstellar material (CSM) at early times, and stronger CSM interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for weak CSM interaction added to the light curve of a normal SN~II-P. This plateau requires that the progenitor had an extended H envelope like a red supergiant, consistent with the slow progenitor wind speed indicated by narrow emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum --- meaning that the presence of such WR features in an early SN spectrum does not necessarily indicate a WR-like progenitor. [abridged] Overall, PTF11iqb bridges SNe~IIn with weaker pre-SN mass loss seen in SNe II-L and II-P, implying a continuum between these types.Comment: 21 pages, 12 figures, submitted to MNRA

Enriching for rumen bacteria to degrade the Pimelea plant toxin simplexin, in an anaerobic in vitro fermenter

Three species of Australian native plants, Pimelea trichostachya, P. simplex and P. elongata, are endemic to the arid rangelands of Queensland, New South Wales and South Australia and are responsible for Pimelea poisoning, also known as St George or Marree disease. Pimelea poisoning occurs in cattle ingesting Pimelea plants, with the orthoester simplexin identified as the responsible toxin. There is no effective treatment and economic losses have been estimated at over $50 million during significant Pimelea poisoning events. In a previous feeding trial, animals were fed increasing amounts of Pimelea, and after initially showing signs of poisoning, the animals appeared to adapt to ingesting Pimelea, possibly through rumen microbial degradation of the toxin (Fletcher et al., 2014). Kangaroos, forestomach fermenters, often graze pastures containing Pimelea with no apparent ill effects. To investigate the degradation effect further, a series of 30 day in vitro, anaerobic fermentations were undertaken

Endothelin.

The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action. Highly selective peptide ETA and ETB antagonists and ETB agonists together with radiolabeled analogs have accurately delineated endothelin pharmacology in humans and animal models, although surprisingly no ETA agonist has been discovered. ET antagonists (bosentan, ambrisentan) have revolutionized the treatment of pulmonary arterial hypertension, with the next generation of antagonists exhibiting improved efficacy (macitentan). Clinical trials continue to explore new applications, particularly in renal failure and for reducing proteinuria in diabetic nephropathy. Translational studies suggest a potential benefit of ETB agonists in chemotherapy and neuroprotection. However, demonstrating clinical efficacy of combined inhibitors of the endothelin converting enzyme and neutral endopeptidase has proved elusive. Over 28 genetic modifications have been made to the ET system in mice through global or cell-specific knockouts, knock ins, or alterations in gene expression of endothelin ligands or their target receptors. These studies have identified key roles for the endothelin isoforms and new therapeutic targets in development, fluid-electrolyte homeostasis, and cardiovascular and neuronal function. For the future, novel pharmacological strategies are emerging via small molecule epigenetic modulators, biologicals such as ETB monoclonal antibodies and the potential of signaling pathway biased agonists and antagonists.We (APD, JJM) thank the British Heart Foundation (PS/02/001, PG/05/127/19872, FS/12/64/130001), Wellcome Trust Programme in Metabolic and Cardiovascular Disease 096822/Z/11/Z NIHR Cambridge Biomedical Research Centre and the Pulmonary Hypertension Association UK; Wellcome Biomedical Resources Grant 099156/Z/12/Z for support for IUPHAR/BPS Guide to PHARMACOLOGY (CS). We acknowledge National Heart, Lung, and Blood Institute Grants P01 HL95499 (D.E.K., K.A.H., D.M.P., J.S.P.), P01 HL69999 (D.M.P., J.S.P.), U01HL117684 (D.M.P.).This is the final version of the article. It first appeared from the American Society for Pharmacology and Experimental Therapeutics via https://doi.org/10.1124/pr.115.01183

Additions to Philippine slender skinks of the Brachymeles bonitae complex (Reptilia: Squamata: Scincidae) IV: Resurrection and redescription of Brachymeles burksi

The diversity of Philippine amphibians and reptiles has increased over the last few decades, in part due to re-evaluation of species formerly believed to be widespread. Many of these investigations of widespread species have uncovered multiple closely related cryptic lineages comprising species complexes, each restricted to individual Pleistocene Aggregate Island Complexes (PAICs). One group in particular for which widespread cryptic diversity has been common is the clade of Philippine skinks of the genus Brachymeles. Recent phylogenetic studies of the formerly recognized widespread species Brachymeles bonitae have indicated that this species is actually a complex distributed across several major PAICs and smaller island groups in the central and northern Philippines, with numerous species that exhibit an array of digit loss and limb reduction patterns. Despite the recent revisions to the B. bonitae species complex, studies suggest that unique cryptic lineages still exist within this group. In this paper, we resurrect the species Brachymeles burksi Taylor 1917, for a lineage of non-pentadactyl, semi-fossorial skink from Mindoro and Marinduque islands. First described in 1917, B. burksi was synonymized with B. bonitae in 1956, and has rarely been reconsidered since. Evaluation of genetic and morphological data (qualitative traits, meristic counts, and mensural measurements), and comparison of recently-obtained specimens to Taylor’s original description support this species’ recognition, as does its insular distribution on isolated islands in the central portions of the archipelago. Morphologically, B. burksi is differentiated from other members of the genus based on a suite of unique phenotypic characteristics, including a small body size, digitless limbs, a high number of presacral vertebrae, the absence of auricular openings, and discrete (non-overlapping) meristic scale counts. The recognition of this central Philippine species further increases the diversity of non-pentadactyl members of the B. bonitae complex, and reinforces the biogeographic uniqueness of the Mindoro faunal region

Dyspnea Review for the Palliative Care Professional: Treatment Goals and Therapeutic Options

Although dyspnea is frequently encountered in the palliative care setting, its optimal management remains uncertain. Clinical approaches begin with accurate assessment, as delineated in part one of this two-part series. Comprehensive dyspnea assessment, which encompasses the physical, emotional, social, and spiritual aspects of this complex symptom, guide the clinician in choosing therapeutic approaches herein presented as part two. Global management of dyspnea is appropriate both as complementary to disease-targeted treatments that target the underlying etiology, and as the sole focus when the symptom has become intractable, disease is maximally treated, and goals of care shift to comfort and quality of life. In this setting, current evidence supports the use of oral or parenteral opioids as the mainstay of dyspnea management, and of inhaled furosemide and anxiolytics as adjuncts. Nonpharmacologic interventions such as acupuncture and pulmonary rehabilitation have potential effectiveness, although further research is needed, and use of a simple fan warrants consideration given its potential benefit and minimal burden and cost

Dyspnea Review for the Palliative Care Professional: Assessment, Burdens, and Etiologies

Dyspnea is a common symptom experienced by many patients with chronic, life-threatening, and/or life-limiting illnesses. Although it can be defined and measured in several ways, dyspnea is best described directly by patients through regular assessment, as its burdens exert a strong influence on the patient's experience throughout the trajectory of serious illness. Its significance is amplified due to its impact on family and caregivers