Culture, conditions and care support mental health of healthcare workers during crises.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has presented immense challenges to health systems worldwide and significantly impacted the mental health of frontline healthcare workers. AIMS: This study drew on the experiences of frontline healthcare workers to examine organizational strategies needed to support the mental health and well-being of healthcare workers during times of crisis. METHODS: Semi-structured focus groups or individual interviews were conducted with healthcare workers to examine their perspectives on organizational strategies for enhancing staff mental health and well-being during crises. Data were analysed thematically. Following this, evidence for the identified strategies was reviewed to assess alignment with participant views and recommendations. RESULTS: Thirty-two healthcare workers from diverse disciplines (10 allied health, 11 nursing, 11 medical) participated in the study. Data analysis identified three broad themes contributing to supporting mental health and well-being. These themes can be encapsulated as the 'Three Cs'-culture (building an organizational culture that prioritizes mental health); conditions (implementing proactive organizational strategies during crises) and care (ensuring fit-for-purpose strategies to support mental health and well-being). CONCLUSIONS: Study findings underscore the necessity of an integrated and systemic organizational approach to address mental health and well-being in the healthcare workplace. This approach must be long term with the components of the 'Three Cs', particularly cultural change and conditions, viewed as a part of a suite of strategies to ensure crisis preparedness. It is imperative that organizations collaborate with their staff, providing support and fostering a safe and inclusive work environment that ultimately benefits patients, their care and staff well-being.

The global distribution of plants used by humans.

Plants sustain human life. Understanding geographic patterns of the diversity of species used by people is thus essential for the sustainable management of plant resources. Here, we investigate the global distribution of 35,687 utilized plant species spanning 10 use categories (e.g., food, medicine, material). Our findings indicate general concordance between utilized and total plant diversity, supporting the potential for simultaneously conserving species diversity and its contributions to people. Although Indigenous lands across Mesoamerica, the Horn of Africa, and Southern Asia harbor a disproportionate diversity of utilized plants, the incidence of protected areas is negatively correlated with utilized species richness. Finding mechanisms to preserve areas containing concentrations of utilized plants and traditional knowledge must become a priority for the implementation of the Kunming-Montreal Global Biodiversity Framework.

GPR-160 Receptor Signaling in the Dorsal Vagal Complex of Male Rats Modulates Meal Microstructure and CART-Mediated Hypophagia.

The g-protein coupled receptor GPR-160, recently identified as a putative receptor for the cocaine and amphetamine-regulated transcript (CART) peptide, shows abundant expression in the energy-balance control nuclei, including the dorsal vagal complex (DVC). However, its physiological role in the control of food intake has yet to be fully explored. Here, we performed a virally mediated, targeted knockdown (KD) of Gpr160 in the DVC of male rats to evaluate its physiological role in control of feeding. Our results indicate that DVC Gpr160 KD affects meal microstructure. Specifically, DVC Gpr160 KD animals consumed more frequent, but shorter meals during the dark phase and showed decreased caloric intake and duration of meals during the light phase. Cumulatively, however, these bidirectional effects on feeding resulted in no difference in body weight gain. We next tested the role of DVC GPR-160 in mediating the anorexigenic effects of exogenous CART. Our results show that DVC Gpr160 KD partially attenuates CART's anorexigenic effects. To further characterize Gpr160+ cells in the DVC, we utilized single-nucleus RNA sequencing data to uncover abundant GPR-160 expression in DVC microglia and only minimal expression in neurons. Altogether, our results suggest that DVC CART signaling may be mediated by Gpr160+ microglia, which in turn may be modulating DVC neuronal activity to control food intake.

Exploring views of members of the public and policymakers on the acceptability of population level dietary and active-travel policies: a qualitative study.

BACKGROUND: There is limited evidence on what shapes the acceptability of population level dietary and active-travel policies in England. This information would be useful in the decision-making process about which policies should be implemented and how to increase their effectiveness and sustainability. To fill this gap, we explored public and policymakers' views about factors that influence public acceptability of dietary and active-travel policies and how to increase public acceptability for these policies. METHODS: We conducted online, semi-structured interviews with 20 members of the public and 20 policymakers in England. A purposive sampling frame was used to recruit members of the public via a recruitment agency, based on age, sex, socioeconomic status and ethnicity. Policymakers were recruited from existing contacts within our research collaborations and via snowball sampling. We explored different dietary and active-travel policies that varied in their scope and focus. Interviews were transcribed verbatim and analysed using thematic reflexive analysis with both inductive and deductive coding. RESULTS: We identified four themes that informed public acceptability of dietary and active-travel policies: (1) perceived policy effectiveness, i.e., policies that included believable mechanisms of action, addressed valued co-benefits and barriers to engage in the behaviour; (2) perceived policy fairness, i.e., policies that provided everyone with an opportunity to benefit (mentioned only by the public), equally considered the needs of various population subgroups and rewarded 'healthy' behaviours rather than only penalising 'unhealthy' behaviours; (3) communication of policies, i.e., policies that were visible and had consistent and positive messages from the media (mentioned only by policymakers) and (4) how to improve policy support, with the main suggestion being an integrated strategy addressing multiple aspects of these behaviours, inclusive policies that consider everyone's needs and use of appropriate channels and messages in policy communication. CONCLUSIONS: Our findings highlight that members' of the public and policymakers' support for dietary and active-travel policies can be shaped by the perceived effectiveness, fairness and communication of policies and provide suggestions on how to improve policy support. This information can inform the design of acceptable policies but can also be used to help communicate existing and future policies to maximise their adoption and sustainability.

The actions of C-peptide in HEK293 cells are dependent upon insulin and extracellular glucose concentrations.

Connecting peptide, or C-peptide, is a part of the insulin prohormone and is essential for the proper folding and processing of the mature insulin peptide. C-peptide is released from the same beta cell secretory granules as insulin in equimolar amounts. However, due to their relative stabilities in plasma, the two peptides are detected in the circulation at ratios of approximately 4:1 to 6:1 (C-peptide to insulin), depending on metabolic state. C-peptide binds specifically to human cell membranes and induces intracellular signaling cascades, likely through an interaction with the G protein coupled receptor, GPR146. C-peptide has been shown to exert protective effects against the vascular, renal, and ocular complications of diabetes. The effects of C-peptide appear to be dependent upon the presence of insulin and the absolute, extracellular concentration of glucose. In this study, we employed HEK293 cells to further examine the interactive effects of C-peptide, insulin, and glucose on cell signaling. We observed that C-peptide's cellular effects are dampened significantly when cells are exposed to physiologically relevant concentrations of both insulin and C-peptide. Likewise, the actions of C-peptide on cFos and GPR146 mRNA expressions were affected by changes in extracellular glucose concentration. In particular, C-peptide induced significant elevations in cFos expression in the setting of high (25 mmol) extracellular glucose concentration. These data indicate that future experimentation on the actions of C-peptide should control for the presence or absence of insulin and the concentration of glucose. Furthermore, these findings should be considered prior to the development of C-peptide-based therapeutics for the treatment of diabetes-associated complications.

The Deductive Reasoning Strategy Enables Biomedical Breakthroughs.

G protein-coupled receptors (GPCRs) transmit the signals of a variety of hormones and neurotransmitters and are targets of more than 30% of all FDA-approved drugs. We developed an approach for identifying the endogenous ligands for a family of orphan GPCRs that enables the development of novel therapeutics for the potential treatment of a wide variety of disorders including pain, diabetes, appetitive behaviors, infertility and obesity. With this approach, we have deorphanized five previously orphaned GPCRs.

Overcoming Stress, Hunger, and Pain: Cocaine- and Amphetamine-Regulated Transcript Peptide's Promise.

Cocaine- and amphetamine-regulated transcript encodes an eponymous peptide, CARTp, which exerts diverse pharmacologic actions in the central and peripheral nervous systems, as well as in several endocrine organs, including pancreas. Here we review those diverse actions, the physiological relevance of which had remained unestablished until recently. With the identification of a CARTp receptor, GPR160, the physiologic importance and therapeutic potential of CARTp or analogs are being revealed. Not only is the CARTp-GPR160 interaction essential for the circadian regulation of appetite and thirst but also for the transmission of nerve injury-induced pain. Molecular approaches now are uncovering additional physiologically relevant actions and the development of acute tissue-specific gene compromise approaches may reveal even more physiologically relevant actions of this pluripotent ligand/receptor pair.

Past, present and future of cocaine- and amphetamine-regulated transcript peptide.

The existence of the peptide encoded by the cocaine- and amphetamine-regulated transcript (Cartpt) has been recognized since 1981, but it was not until 1995, that the gene encoding CART peptide (CART) was identified. With the availability of the predicted protein sequence of CART investigators were able to identify sites of peptide localization, which then led to numerous approaches attempting to clarify CART's multiple pharmacologic effects and even provide evidence of potential physiologic relevance. Although not without controversy, a picture emerged of the importance of CART in ingestive behaviors, reward behaviors and even pain sensation. Despite the wealth of data hinting at the significance of CART, in the absence of an identified receptor, the full potential for this peptide or its analogs to be developed into therapeutic agents remained unrealized. There was evidence favoring the action of CART via a G protein-coupled receptor (GPCR), but despite multiple attempts the identity of that receptor eluded investigators until recently. Now with the identification of the previously orphaned GPCR, GPR160, as a receptor for CART, focus on this pluripotent neuropeptide will in all likelihood experience a renaissance and the potential for the development of pharmcotherapies targeting GPR160 seems within reach.

State and local pressures drive plastic pollution compliance strategies.

Environmental harm from plastic pollution partly results from compliance failure at the individual level. Three prevalent non-compliant motivations for polluting plastics include economic gains, ignorance of the rules and unlikely penalization from inadequately enforced rules. Given compliance is primarily the responsibility of local waste management, we conducted interviews to gain insights to the factors driving changes in the crucial on-ground controls of plastic pollution. We expand on non-compliant motivations and provide a theoretical framework to test the aforementioned. We show that compliance strategies are strongly driven by state judicial and economic controls, specifically new plastic legislation and levies. Furthermore, the priorities of waste managers and the socio-economics and population density of their constituents drove changes in local management efforts. Our findings support the view that the growing global attention on plastic pollution shapes not only what happens at a state level, but also importantly on-ground at the local level.

Signaling in rat brainstem via Gpr160 is required for the anorexigenic and antidipsogenic actions of cocaine- and amphetamine-regulated transcript peptide.

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food intake and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacological dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food intake and water intake. Blockade of Gpr160 in the 4V, independent of pharmacological CART treatment, caused an increase in both overnight food intake and water intake. The decrease in food intake, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a glucagon-like peptide 1 (GLP-1) receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and nonneuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection and extend these findings to water drinking. Gpr160ir was observed in both neuronal and nonneuronal cell types in regions known to be important in the multiple pharmacological effects of CARTp, identifying those areas as targets for future compromise of function studies.

Seroprevalence of Brucella canis in dogs rescued from South Dakota Indian reservations, 2015-2019.

Canine brucellosis, caused by Brucella canis, is an infectious disease with implications for canine as well as human health. The identification of infected dogs originating from and around two South Dakota Indian reservations prompted an examination of the seroprevalence of B. canis in stray or owner-surrendered dogs from these communities. Using results from in-clinic screening tests of 3898 dogs over more than 4 years, we determined an overall apparent B. canis seroprevalence of 6.8% (adjusted estimated true prevalence of 29.4%), with rates declining over time. The apparent rate was similar to other surveys of stray dog populations in the US. Older dogs were significantly more likely to be B. canis-positive than younger dogs, as were reproductively intact dogs versus altered dogs (although this difference was not statistically significant). There were geographic differences in seropositive rates as well, with higher rates found in dogs originating from one reservation compared to other locations. Current diagnostic tests lack sensitivity to effectively identify all B. canis-infected dogs, but results from this study are valuable for investigating differences among risk factors for infection. Because of the potential for B. canis to infect other dogs and people, stray dog populations should be screened for B. canis before those animals are placed in adoptive homes.

A new malaria vector in Africa: Predicting the expansion range of Anopheles stephensi and identifying the urban populations at risk.

In 2012, an unusual outbreak of urban malaria was reported from Djibouti City in the Horn of Africa and increasingly severe outbreaks have been reported annually ever since. Subsequent investigations discovered the presence of an Asian mosquito species; Anopheles stephensi, a species known to thrive in urban environments. Since that first report, An. stephensi has been identified in Ethiopia and Sudan, and this worrying development has prompted the World Health Organization (WHO) to publish a vector alert calling for active mosquito surveillance in the region. Using an up-to-date database of published locational records for An. stephensi across its full range (Asia, Arabian Peninsula, Horn of Africa) and a set of spatial models that identify the environmental conditions that characterize a species' preferred habitat, we provide evidence-based maps predicting the possible locations across Africa where An. stephensi could establish if allowed to spread unchecked. Unsurprisingly, due to this species' close association with man-made habitats, our maps predict a high probability of presence within many urban cities across Africa where our estimates suggest that over 126 million people reside. Our results strongly support the WHO's call for surveillance and targeted vector control and provide a basis for the prioritization of surveillance.

A novel regulator of thirst behavior: phoenixin.

There are examples of physiological conditions under which thirst is inappropriately exaggerated, and the mechanisms for these paradoxical ingestive behaviors remain unknown. We are interested in thirst mechanisms across the female life cycle and have identified a novel mechanism through which ingestive behavior may be activated. We discovered a previously unrecognized endogenous hypothalamic peptide, phoenixin (PNX), identified physiologically relevant actions of the peptide in brain and pituitary gland to control reproductive hormone secretion in female rodents, and in the process identified the previously orphaned G protein-coupled receptor Gpr173 to be a potential receptor for the peptide. Labeled PNX binding distribution in brain parallels areas known to be important in ingestive behaviors as well in areas where gonadal steroids feedback to control estrous cyclicity (Stein LM, Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GLC, Am J Physiol Regul Integr Comp Physiol 311: R489-R496, 2016). We have demonstrated upregulation of Gpr173 during puberty, fluctuations across the estrous cycle, and, importantly, upregulation during the last third of gestation. It is during this hypervolemic, hyponatremic state that both vasopressin secretion and thirst are inappropriately elevated in humans. Here, we show that central administration of PNX stimulated water drinking in both males and females under ad libitum conditions, increased water drinking after overnight fluid deprivation, and increased both water and 1.5% NaCl ingestion under fed and hydrated conditions. Importantly, losartan pretreatment blocked the effect of PNX on water drinking, and knockdown of Gpr173 by use of short interfering RNA constructs significantly attenuated water drinking in response to overnight fluid deprivation. These actions, together with the stimulatory action of PNX on vasopressin secretion, suggest that this recently discovered neuropeptide may impact the recruitment of critically important neural circuits through which ingestive behaviors and endocrine mechanisms that maintain fluid and electrolyte homeostasis are regulated.

Identifying drivers of forest resilience in long-term records from the Neotropics.

Here, we use 30 long-term, high-resolution palaeoecological records from Mexico, Central and South America to address two hypotheses regarding possible drivers of resilience in tropical forests as measured in terms of recovery rates from previous disturbances. First, we hypothesize that faster recovery rates are associated with regions of higher biodiversity, as suggested by the insurance hypothesis. And second, that resilience is due to intrinsic abiotic factors that are location specific, thus regions presently displaying resilience in terms of persistence to current climatic disturbances should also show higher recovery rates in the past. To test these hypotheses, we applied a threshold approach to identify past disturbances to forests within each sequence. We then compared the recovery rates to these events with pollen richness before the event. We also compared recovery rates of each site with a measure of present resilience in the region as demonstrated by measuring global vegetation persistence to climatic perturbations using satellite imagery. Preliminary results indeed show a positive relationship between pre-disturbance taxonomic richness and faster recovery rates. However, there is less evidence to support the concept that resilience is intrinsic to a region; patterns of resilience apparent in ecosystems presently are not necessarily conservative through time.

GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents.

Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.