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.

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.

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.

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.

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.

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.

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.

Expression and function of nesfatin-1 are altered by stage of the estrous cycle.

Nesfatin-1 is a peptide derived from the nucleobindin 2 (Nucb2) precursor protein that has been shown to exert potent effects on appetite and cardiovascular function in male animals. Sex hormones modulate the expression of Nucb2 in several species, including goldfish, mouse, and rat, and human studies have revealed differential expression based on male or female sex. We therefore hypothesized that the ability of nesfatin-1 to increase mean arterial pressure (MAP) would be influenced by stage of the estrous cycle. Indeed, we found that in cycling female Sprague-Dawley rats, nesfatin-1 induced an increase in MAP on diestrus, when both estrogen and progesterone levels are low but not on proestrus or estrus. The effect of nesfatin-1 on MAP was dependent on functional central melanocortin receptors, because the nesfatin-1-induced increase in MAP was abolished by pretreatment with the melanocortin 3/4 receptor antagonist, SHU9119. We previously reported that nesfatin-1 inhibited angiotensin II-induced water drinking in male rats but found no effect of nesfatin-1 in females in diestrus. However, nesfatin-1 enhanced angiotensin II-induced elevations in MAP in females in diestrus but had no effect on males. Finally, in agreement with previous reports, the expression of Nucb2 mRNA in hypothalamus was significantly reduced in female rats in proestrus compared with rats in diestrus. From these data we conclude that the function and expression of nesfatin-1 are modulated by sex hormone status. Further studies are required to determine the contributions of chromosomal sex and individual sex hormones to the cardiovascular effects of nesfatin-1.

The Effects of Pre-treatment Depressive Symptoms on Quality of Life Across Cognitive Behavioral Therapy for Chronic Pain.

Recent studies suggest that chronic pain affects millions and carries significant physical, financial, and social burdens, and thus adversely affects quality of life (QOL). Cognitive behavioral therapy for chronic pain (CBTp) is a non-pharmacological treatment method which has been shown to reduce a sufferer's experience of chronic pain and improve overall QOL. These and other studies also indicate that affective symptoms likely impact the effectiveness of CBTp. The current study focused on the effects of depressive symptoms on changes in QOL ratings across a 12-session CBT for chronic pain. Participants in this study (n = 313; mean age = 46.83 years, SD = 10.99, range = 19.1-79.9, 63.9% female, 83.9% Caucasian) were current patients of a mid-sized tertiary multidisciplinary outpatient chronic pain treatment facility. Progress through CBTp was assessed using QOL as a dependent variable and analyzed using RMANOVAs. All participants showed improvements in QOL ratings across the CBTp period, but greater improvements were seen in participants in the low depression category than in the high or moderate depression category. This study also confirms the clinical utility of the BDI-II with chronic pain patients.

Novel regulator of vasopressin secretion: phoenixin.

The newly described hypothalamic peptide, phoenixin, is produced in the hypothalamus and adenohypophysis, where it acts to control reproductive hormone secretion. Both phoenixin and its receptor GPR173 are expressed in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, suggesting additional, nonreproductive effects of the peptide to control vasopressin (AVP) or oxytocin (OT) secretion. Hypothalamo-neurohypophysial explants released AVP but not OT in response to phoenixin. Intracerebroventricular administration of phoenixin into conscious, unrestrained male and female rats significantly increased circulating AVP, but not OT, levels in plasma, and it increased immediate early gene expression in the supraoptic nuclei of male rats. Bath application of phoenixin in hypothalamic slice preparations resulted in depolarization of PVN neurons, indicating a direct, neural action of phoenixin in the hypothalamus. Our results suggest that the newly described, hypothalamic peptide phoenixin, in addition to its effects on hypothalamic and pituitary mechanisms controlling reproduction, may contribute to the physiological mechanisms regulating fluid and electrolyte homeostasis.

Evaluating the impact of two training interventions to improve diagnosis and case-management of malaria and pneumonia in Uganda.

We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14-91% in reduction of disease cases.

A 5'-upstream short open reading frame encoded peptide regulates angiotensin type 1a receptor production and signalling via the ß-arrestin pathway.

AUG sequences and short open reading frames are commonly present in the 5'-leader sequence of G protein-coupled receptor mRNAs. The presence of these upstream AUG sequences has been demonstrated to inhibit downstream receptor translation efficiency and, most recently, receptor signal transduction. A seven amino acid peptide encoded by a short open reading frame in exon 2 of the angiotensin type 1a receptor has been shown to inhibit non-G protein-coupled signalling of angiotensin II, without altering the classical G protein-coupled pathway activated by the ligand. This finding may lead to the development of a new class of angiotensin receptor antagonists with activities biased for one, but not all, of the signalling cascades activated by angiotensin II, which could have therapeutic implications for the myriad hormones and neurotransmitters that signal through G protein-coupled receptors.

Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19.

Adropin, a recently described peptide hormone produced in the brain and liver, has been reported to have physiologically relevant actions on glucose homeostasis and lipogenesis, and to exert significant effect on endothelial function. We describe a central nervous system action of adropin to inhibit water drinking and identify a potential adropin receptor, the orphan G protein-coupled receptor, GPR19. Reduction in GPR19 mRNA levels in medial basal hypothalamus of male rats resulted in the loss of the inhibitory effect of adropin on water deprivation-induced thirst. The identification of a novel brain action of adropin and a candidate receptor for the peptide should extend and accelerate the study of the potential therapeutic value of adropin or its mimetics for the treatment of metabolic disorders.

Neuronostatin acts via GPR107 to increase cAMP-independent PKA phosphorylation and proglucagon mRNA accumulation in pancreatic α-cells.

Neuronostatin (NST) is a recently described peptide that is produced from the somatostatin preprohormone in pancreatic δ-cells. NST has been shown to increase glucagon secretion from primary rat pancreatic islets in low-glucose conditions. Here, we demonstrate that NST increases proglucagon message in α-cells and identify a potential mechanism for NST's cellular activities, including the phosphorylation of PKA following activation of the G protein-coupled receptor, GPR107. GPR107 is abundantly expressed in the pancreas, particularly, in rodent and human α-cells. Compromise of GPR107 in pancreatic α-cells results in failure of NST to increase PKA phosphorylation and proglucagon mRNA levels. We also demonstrate colocalization of GPR107 and NST on both mouse and human pancreatic α-cells. Taken together with our group's observation that NST infusion in conscious rats impairs glucose clearance in response to a glucose challenge and that plasma levels of the peptide are elevated in the fasted compared with the fed or fasted-refed state, these studies support the hypothesis that endogenous NST regulates islet cell function by interacting with GPR107 and initiating signaling in glucagon-producing α-cells.

Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats.

To investigate age-associated impairments in fluid homeostasis, 4-mo (young) and 32-mo (old) Fischer 344/BN male rats were studied before and after a dietary sodium load. Transferring young rats from a low-sodium (LS) to a high-sodium (HS) diet increased water intake and urine volume by 1.9- and 3.0-fold, respectively, while urine osmolality and plasma aldosterone decreased by 33 and 98%. Concomitantly, adrenocortical angiotensin type 1 receptor (AT1R) density decreased by 35%, and AT1bR mRNA decreased by 39%; no changes were observed in AT1aR mRNA. In contrast, the increase in water intake (1.4-fold) was lower in the old rats, and there was no effect of the HS diet on urine volume or urine osmolality. AT1R densities were 29% less in the old rats before transferring to the HS diet, and AT1R densities were not reduced as rapidly in response to a HS diet compared with the young animals. After 6 days on the HS diet, plasma potassium was lowered by 26% in the old rats, whereas no change was detected in the young rats. Furthermore, while plasma aldosterone was substantially decreased after 2 days on the HS diet in both young and old rats, plasma aldosterone was significantly lower in the old compared with the young animals after 2 wk on the LS diet. These findings suggest that aging attenuates the responsiveness of the adrenocortical AT1R to a sodium load through impaired regulation of AT1bR mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.

Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173.

Sexual maturation and maintenance of reproductive function are regulated by neurohormonal communication between the hypothalamus, pituitary, and gonads (referred to as the HPG axis). Phoenixin (PNX) is a newly identified, endogenous peptide abundantly produced in the hypothalamus and shown to be an important mediator of ovarian cyclicity. However, the underlying mechanisms by which phoenixin functions within the HPG axis are unknown. Previous in vitro studies demonstrated a direct action of PNX on gonadotrophs to potentiate gonadotrophin-releasing hormone (GnRH) induced luteinizing hormone (LH) secretion. Therefore, we hypothesized that centrally derived phoenixin regulates the preovulatory LH surge required for ovarian cyclicity. We observed a significant dose-related increase in the level of plasma LH in diestrous, female rats that were given an intracerebroventricular injection of PNX compared with vehicle-treated controls. While this suggests that even under low-estrogen conditions, PNX acts centrally to stimulate the HPG axis, further characterization is contingent on the elucidation of its cognate receptor. Using the "deductive ligand receptor matching strategy," we identified the orphan G protein-coupled receptor, Gpr173, as our top candidate. In cultured pituitary cells, siRNA-targeted compromise of Gpr173 abrogated PNX's action to potentiate GnRH-stimulated LH secretion. In addition, siRNA-mediated knockdown of endogenous Gpr173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats. These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.