Changing characteristics of patients with palliative care needs in acute hospitals.

BACKGROUND: Palliative care services drastically changed over the course of the COVID-19 pandemic between the years 2020 to 2022. AIM: To report on the changes in a specialist palliative care hospital liaison service (SPCHLS) during the COVID-19 pandemic, and consider the impact of this for longer term service modelling. METHODS: A retrospective analysis of patients admitted via the emergency department (ED) in January 2020 and 2021, who were given a palliative care 'code' at the end of their episode of care. Data were collected using electronic records and descriptive statistics were used. FINDINGS: The total number of patients seen in the ED increased by 30%, with a 185% increase in death as an outcome of admission. A total of 50% of patients were seen by a member of the SPCHLS in the ED in 2021, compared to just 28% in 2020. There was a 46% increase in the number of patients transferred to a Specialist Palliative Care Unit. CONCLUSIONS: Delayed diagnoses, long waiting times and changing community services lead to increased pressure and a requirement to meet palliative care needs in acute hospitals. There is a growing need for acute palliative care services to meet the needs of the population.

Methods for Investigating Transient Receptor Potential Melastatin-2 (TRPM2): A Cation Channel Activated by ADP-Ribose and Involved in Cell Death.

Transient receptor potential melastatin-2 (TRPM2) is an emerging chemotherapeutic target due to its involvement in poly(ADP-ribose) metabolism and the ability to induce anticancer effects after antagonism of its functions. Normally functioning as a nonspecific cation channel that is activated by free ADP-ribose, TRPM2 is involved with many cellular processes, including the induction of cell death after oxidative stress. What is becoming clear is that antagonism of TRPM2 selectively induces anticancer effects in several types of cancer. We previously demonstrated decreased growth and proliferation, increased levels of DNA damage, and the selective induction of cell death in breast cancer and melanoma cells. Due to these effects, it appears that TRPM2 has a novel role in cancer cells. Further, this novel role appears to involve nuclear function, because our studies, as well as those from other independent groups, demonstrate a nuclear localization of TRPM2 in various types of cancers. Thus, as an emerging therapeutic target, it is important to describe research techniques that can be utilized to analyze TRPM2 function, determine its effects in cancerous and noncancerous cells, and provide molecular biological methods to inhibit or downregulate its function.

Exotic asphyxiation: interactions between invasive species and hypoxia.

Non-indigenous species (NIS) and hypoxia (<2 mg O2 l-1 ) can disturb and restructure aquatic communities. Both are heavily influenced by human activities and are intensifying with global change. As these disturbances increase, understanding how they interact to affect native species and systems is essential. To expose patterns, outcomes, and generalizations, we thoroughly reviewed the biological invasion literature and compiled 100 studies that examine the interaction of hypoxia and NIS. We found that 64% of studies showed that NIS are tolerant of hypoxia, and 62% showed that NIS perform better than native species under hypoxia. Only one-quarter of studies examined NIS as creators of hypoxia; thus, NIS are more often considered passengers associated with hypoxia, rather than drivers of it. Paradoxically, the NIS that most commonly create hypoxia are primary producers. Taxa like molluscs are typically more hypoxia tolerant than mobile taxa like fish and crustaceans. Most studies examine individual-level or localized responses to hypoxia; however, the most extensive impacts occur when hypoxia associated with NIS affects communities and ecosystems. We discuss how these influences of hypoxia at higher levels of organization better inform net outcomes of the biological invasion process, i.e. establishment, spread, and impact, and are thus most useful to management. Our review identifies wide variation in the way in which the interaction between hypoxia and NIS is studied in the literature, and suggests ways to address the number of variables that affect their interaction and refine insight gleaned from future studies. We also identify a clear need for resource management to consider the interactive effects of these two global stressors which are almost exclusively managed independently.

Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury.

Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed.

Flexible growth and body mass predict physiological condition at fledging in the synchronously breeding European starling, Sturnus vulgaris.

Recent studies have reported beneficial carryover effects of juvenile development that predict interspecific survival differences at independence. Yet, traits relating to body size (i.e. morphological traits) have proven to be unreliable predictors of juvenile survival within species. Exploring individual variation of growth trajectories and how they covary with physiology could reveal species-specific developmental modes which have implications for our assessments of juvenile quality. Here, we investigated morphological development of European starlings (Sturnus vulgaris) approaching fledging in relation to three components of physiological condition at independence: aerobic capacity, energy state and oxidative status. We found evidence of flexible mass and wing growth which independently covaried with fledgling energy state and aerobic capacity, respectively. By comparison, tarsus and wing length at fledging were unrelated to any physiological trait, while mass was positively associated with principal component scores that comprised aerobic capacity and energy state. Thus, flexible growth trajectories were consistent with 'developmental plasticity': adaptive pre-fledging mass recession and compensatory wing growth, which seemingly came at a physiological cost, while fledgling body mass positively reflected overall physiological condition. This highlights how patterns of growth and absolute size may differently reflect fledgling physiology, potentially leading to variable relationships between morphological traits and juvenile fitness.

Role of Nitric Oxide-Releasing Glycosaminoglycans in Wound Healing.

Two glycosaminoglycan (GAG) biopolymers, hyaluronic acid (HA) and chondroitin sulfate (CS), were chemically modified via carbodiimide chemistry to facilitate the loading and release of nitric oxide (NO) to develop a multi-action wound healing agent. The resulting NO-releasing GAGs released 0.2-0.9 µmol NO mg-1 GAG into simulated wound fluid with NO-release half-lives ranging from 20 to 110 min. GAGs containing alkylamines with terminal primary amines and displaying intermediate NO-release kinetics exhibited potent, broad spectrum bactericidal action against three strains each of Pseudomonas aeruginosa and Staphylococcus aureus ranging in antibiotic resistance profile. NO loading of the GAGs was also found to decrease murine TLR4 activation, suggesting that the therapeutic exhibits anti-inflammatory mechanisms. In vitro adhesion and proliferation assays utilizing human dermal fibroblasts and human epidermal keratinocytes displayed differences as a function of the GAG backbone, alkylamine identity, and NO-release properties. In combination with antibacterial properties, the adhesion and proliferation profiles of the GAG derivatives enabled the selection of the most promising wound healing candidates for subsequent in vivo studies. A P. aeruginosa-infected murine wound model revealed the benefits of CS over HA as a pro-wound healing NO donor scaffold, with benefits of accelerated wound closure and decreased bacterial burden attributable to both active NO release and the biopolymer backbone.

Nitric Oxide-Releasing Hyaluronic Acid as an Antibacterial Agent for Wound Therapy.

Taking advantage of their respective wound-healing roles in physiology, the dual activity of hyaluronic acid (HA) and nitric oxide (NO) was combined to create a single-agent wound therapeutic. Carboxylic acid groups of HA (6 and 90 kDa) were chemically modified with a series of alkylamines via carbodiimide chemistry to provide secondary amines for subsequent N-diazeniumdiolate NO donor formation. The resulting NO-releasing HA derivatives stored 0.3-0.6 µmol NO mg-1 and displayed diverse release kinetics (5-75 min NO-release half-lives) under physiological conditions. The 6 kDa HA with terminal primary amines and intermediate release kinetics exhibited broad-spectrum bactericidal activity against common wound pathogens, including planktonic methicillin-resistant Staphylococcus aureus as well as planktonic and biofilm-based multidrug-resistant Pseudomonas aeruginosa. The treatment of infected murine wounds with NO-releasing HA facilitated more rapid wound closure and decreased the quantity of the P. aeruginosa genetic material in the remaining wound tissue. Hyaluronidase readily degraded the HA derivatives, indicating that NO donor modification did not prohibit endogenous biodegradation pathways.

Large carnivore hunting and the social license to hunt.

The social license to operate framework considers how society grants or withholds informal permission for resource extractors to exploit publicly owned resources. We developed a modified model, which we refer to as the social license to hunt (SLH). In it we similarly consider hunters as operators, given that wildlife are legally considered public resources in North America and Europe. We applied the SLH model to examine the controversial hunting of large carnivores, which are frequently killed for trophies. Killing for trophies is widespread, but undertaken by a minority of hunters, and can pose threats to the SLH for trophy-seeking carnivore hunters and potentially beyond. Societal opposition to large carnivore hunting relates not only to conservation concerns but also to misalignment between killing for trophies and dominant public values and attitudes concerning the treatment of animals. We summarized cases related to the killing of grizzly bears (Ursus arctos), wolves (Canis lupus), and other large carnivores in Canada, the United States, and Europe to illustrate how opposition to large carnivore hunting, now expressed primarily on social media, can exert rapid and significant pressure on policy makers and politicians. Evidence of the potential for transformative change to wildlife management and conservation includes proposed and realized changes to legislation, business practice, and wildlife policy, including the banning of some large carnivore hunts. Given that policy is ultimately shaped by societal values and attitudes, research gaps include developing increased insight into public support of various hunting policies beyond that derived from monitoring of social media and public polling. Informed by increased evidence, the SLH model can provide a conceptual foundation for predicting the likelihood of transient versus enduring changes to wildlife conservation policy and practice for a wide variety of taxa and contexts.

Cacería de Grandes Carnívoros y la Licencia Social para Cazar Resumen El marco de trabajo de la licencia social para operar considera cómo la sociedad otorga o restringe permisos informales para que los extractores de recursos puedan explotar los recursos públicos. Desarrollamos un modelo modificado, al cual nos referimos como la licencia social para cazar (LSC). En este modelo consideramos a los cazadores como símiles de los operadores puesto que en América del Norte y en Europa a la fauna se le considera legalmente como recurso público. Aplicamos el modelo de la LSC en un análisis de la cacería controversial de grandes carnívoros, a los cuales con frecuencia se les caza para convertirlos en trofeos. La cacería para trofeos es común pero sólo la realiza una minoría de los cazadores y puede presentar una amenaza para la LSC para los cazadores que cazan carnívoros para trofeos e incluso para otros tipos de cazadores. La oposición social a la cacería de grandes carnívoros se relaciona no sólo con el interés de conservación sino también con la discordancia entre la caza para trofeos y las actitudes y valores públicos dominantes con respecto al trato hacia los animales. Resumimos algunos casos relacionados con la muerte de osos pardos (Ursus arctos), lobos (Canis lupus) y otros grandes carnívoros en Canadá, los Estados Unidos y Europa para mostrar cómo la oposición a la cacería de grandes carnívoros, hoy en día expresada principalmente en las redes sociales, puede ejercer una presión rápida y significativa sobre los políticos y los formuladores de políticas. La evidencia de un potencial de cambio transformador en el manejo y conservación de fauna incluye los cambios propuestos y realizados a la legislación, la práctica comercial y las políticas para la fauna, incluyendo la prohibición de la caza de algunos grandes carnívoros. Ya que las políticas están finalmente moldeadas por las actitudes y los valores sociales, las lagunas en la investigación incluyen el desarrollo de un conocimiento mejorado del respaldo público para varias políticas de cacería más allá del conocimiento derivado del monitoreo de las redes sociales y las encuestas públicas. Si se informa con mucha más evidencia, el modelo de la LSC puede proporcionar una base conceptual para predecir la probabilidad de los cambios transitorios versus los duraderos en las políticas y las prácticas de conservación de fauna para una gama amplia de taxones y contextos.

Variations in an African Grey parrot's speech patterns following ignored and denied requests.

Communicative competence is one measure of an individual's ability to navigate conversations with social partners. The current study explored the possibility of basic communicative competence in a non-mammal speaker, a speech-using African Grey parrot. Spontaneous conversations between one Grey named Cosmo and her caregiver were recorded, from which three corpora (i.e., bodies of text) of Cosmo's vocalizations were developed: (1) Baseline: Vocalizations containing no requests, (2) Ignored Requests: Vocalizations immediately following Cosmo's caregiver ignoring Cosmo's requests, and (3) Denied Requests: Vocalizations immediately following Cosmo's caregiver denying Cosmo's requests. The distributions of social (e.g., "I love you," kiss sounds) and nonsocial (e.g., answering machine beeps, "That's squirrel") vocalizations, as well as speech and nonword vocalizations, were statistically different across the three corpora. Additionally, qualitative analysis of the datasets indicated Cosmo was persistent in repeating vocalizations when denied and ignored, and interrupted her caregiver more often when requests were denied compared to ignored. Neither repetition nor interruption occurred during the Baseline conversations. The data indicate that despite the outcome being the same (i.e., request was unmet), Cosmo treated an ignored request differently than a denied request, modifying her vocalizations in accord with the specific context. Such modification is evidence of basic communicative competence.

Women's use of complementary and alternative medicines during pregnancy: a cross-sectional study.

OBJECTIVE: to determine the prevalence of women's use of complementary and alternative medicines (CAM) during pregnancy in the UK, reasons for use, who recommended CAM, and the characteristics of women that are associated with use of CAM during pregnancy. DESIGN: cross-sectional questionnaire. SETTING: Birmingham Women's Hospital. PARTICIPANTS: 315 postnatal women were surveyed while on the postnatal ward. FINDINGS: the questionnaire response rate was 89% (315/355). CAM use during pregnancy was reported by 180 women (57.1%). CAM users differed significantly from non-CAM users by education level, parity and previous CAM use before pregnancy. Vitamins (34.9%), massage therapy (14.0%), yoga (11.1%) and relaxation (10.2%) were the most commonly reported uses of CAM. 33.0% of women reported they did not disclose their use of CAM to a doctor or midwife, and 81.3% were not asked by their doctor or midwife about their use of CAM during pregnancy. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study found a high prevalence of CAM use during pregnancy, which is within the range of findings of studies from Australia and Germany. It is important that health-care providers routinely ask about CAM use during pregnancy and are able to provide pregnant women with appropriate advice regarding CAM use.

Excitatory actions of GABA mediate severe-hypoxia-induced depression of neuronal activity in the pond snail (Lymnaea stagnalis).

To characterize the effect of severe hypoxia on neuronal activity, long-term intracellular recordings were made from neurones in the isolated central ring ganglia of Lymnaea stagnalis. When a neurone at rest in normoxia was subjected to severe hypoxia, action potential firing frequency decreased by 38% (from 2.4-1.5 spikes s(-1)), and the resting membrane potential hyperpolarized from -70.3 to -75.1 mV. Blocking GABA(A) receptor-mediated synaptic transmission with the antagonist bicuculline methiodide (100 micromol l(-1)) decreased neuronal activity by 36%, and prevented any further changes in response to severe hypoxia, indicating that GABAergic neurotransmission mediates the severe hypoxia-induced decrease in neuronal activity. Puffing 100 micromol l(-1) GABA onto the cell body produced an excitatory response characterized by a transient increase in action potential (AP) firing, which was significantly decreased in severe hypoxia. Perturbing intracellular chloride concentrations with the Na+/K+/Cl- (NKCC1) cotransporter antagonist bumetanide (100 micromol l(-1)) decreased AP firing by 40%, consistent with GABA being an excitatory neurotransmitter in the adult Lymnaea CNS. Taken together, these studies indicate that severe hypoxia reduces the activity of NKCC1, leading to a reduction in excitatory GABAergic transmission, which results in a hyperpolarization of the resting membrane potential (Vm) and as a result decreased AP frequency.