Hypoxia Sensing of ß-Adrenergic Receptor Is Regulated by Endosomal PI3Kγ.

BACKGROUND: Impaired beta-adrenergic receptor (ß1 and ß2AR) function following hypoxia underlies ischemic heart failure/stroke. Activation of PI3Kγ (phosphoinositide 3-kinase γ) by beta-adrenergic receptor leads to feedback regulation of the receptor by hindering beta-adrenergic receptor dephosphorylation through inhibition of PP2A (protein phosphatase 2A). However, little is known about PI3Kγ feedback mechanism in regulating hypoxia-mediated ß1 and ß2AR dysfunction and cardiac remodeling. METHODS: Human embryonic kidney 293 cells or mouse adult cardiomyocytes and C57BL/6 (WT) or PI3Kγ knockout (KO) mice were subjected to hypoxia. Cardiac plasma membranes and endosomes were isolated and evaluated for ß1 and ß2AR density and function, PI3Kγ activity and ß1 and ß2AR-associated PP2A activity. Metabolic labeling was performed to assess ß1 and ß2AR phosphorylation and epinephrine/norepinephrine levels measured post-hypoxia. RESULTS: Hypoxia increased ß1 and ß2AR phosphorylation, reduced cAMP, and led to endosomal accumulation of phosphorylated ß2ARs in human embryonic kidney 293 cells and WT cardiomyocytes. Acute hypoxia in WT mice resulted in cardiac remodeling and loss of adenylyl cyclase activity associated with increased ß1 and ß2AR phosphorylation. This was agonist-independent as plasma and cardiac epinephrine and norepinephrine levels were unaltered. Unexpectedly, PI3Kγ activity was selectively increased in the endosomes of human embryonic kidney 293 cells and WT hearts post-hypoxia. Endosomal ß1- and ß2AR-associated PP2A activity was inhibited upon hypoxia in human embryonic kidney 293 cells and WT hearts showing regulation of beta-adrenergic receptors by PI3Kγ. This was accompanied with phosphorylation of endogenous inhibitor of protein phosphatase 2A whose phosphorylation by PI3Kγ inhibits PP2A. Increased ß1 and ß2AR-associated PP2A activity, decreased beta-adrenergic receptor phosphorylation, and normalized cardiac function was observed in PI3Kγ KO mice despite hypoxia. Compared to WT, PI3Kγ KO mice had preserved cardiac response to challenge with ß1AR-selective agonist dobutamine post-hypoxia. CONCLUSIONS: Agonist-independent activation of PI3Kγ underlies hypoxia sensing as its ablation leads to reduction in ß1- and ß2AR phosphorylation and amelioration of cardiac dysfunction.

Twelve tips for designing, implementing and sustaining interprofessional training units on hospital wards.

Dedicated Interprofessional Training Units (ITUs) in hospital wards are one way to prepare healthcare students for Interprofessional patient-centered care. Based on theoretical foundations, research, and our lived experiences of successes as well as failures, we propose 12 tips on how to prepare, implement, and sustain a dedicated ITU, combining the Grol & Wensing model for planning change with the Self-determination Theory of motivation. Start with a steering group, with a dedicated project leader, to translate awareness of the need for an ITU into wider awareness and motivation among stakeholders, with the ITU being a solution to authentic problems. Create shared ownership by jointly formulating feasible educational goals and starting with a pilot to provide opportunities for change. Motivate all stakeholders by stimulating their autonomy, interprofessional competence as well as relatedness to each other, in line with the Self-determination Theory. Confirm the value of the ITU at all stages and embed the ITU in the organizational strategy.

Sustenance of Himalayan springs in an emerging water crisis.

Springs are a significant source of high quality and perennial freshwater supply for remote communities and sustain rich biodiversity and ecosystems in the Himalayas. About 60-70% of the Himalayan population directly depends on springs to meet their domestic and livelihood needs. Despite that, decline in approximately 60% of low discharge springs have been reported in the last couple of decades. In addition, nitrates and faecal coliform contamination linked to septic tanks, open defecation, and fertiliser application have been reported. A high degree of urbanization with 500 growing townships and 8-10 large cities has further threatened the sustenance of these vital resources, causing a severe water crisis in the Himalayas. Spring rejuvenation can enhance water access and livelihoods and help achieve several sustainable development goals (SDGs). However, multiple challenges hinder the success of such initiatives. A fundamental limitation is the poor understanding of complex groundwater (spring) systems and their interactions with human societies. This review identified crucial knowledge gaps by synthesizing available knowledge on springs and revival efforts from peer-reviewed journals and reports by practitioners and governing bodies. The review also highlights the limitations of spring revival approaches and recommends future management options. There is a critical lack of comprehensive data as a large research on the Himalayan spring systems results from small-scale spring centric studies focussing primarily on hydrology. In contrast, the impacts of hydrogeology, ecology, socio-economics and developmental activities on springs are less explored. Lack of scientific inputs on the hydrogeological regime and limited support by the state is a barrier to scaling spring rejuvenation programs. Long term monitoring, location-specific mapping of local hydrogeological and socio-economic settings at aquifer scale and collaborations among different stakeholders are essential to facilitate holistic knowledge development on spring systems and successful spring revival. The authors recommend ensuring sustenance by recognizing the value of springs in the mainstream programs and policies and develop appropriate management framework for the management of spring systems.

Mini review: possible role of the multi-theory model of health behavior change in designing substance use prevention and treatment interventions.

Many behavior change theories have evolved over time. Originally, the first conceptions prioritized interventions based on information, such as raising awareness and transferring knowledge. Second-generation theories prioritize the development of skills and the promotion of awareness. The emergence of evidence-based techniques in the 1990s gave rise to third-generation theories such as the Theory of Planned Behavior and Social Cognitive Theory. Presently, fourth-generation trends amalgamate various components from multiple theories to implement accurate treatments, employing technology and emphasizing targeted behavior change. This paper aims to do a concise evaluation of the multi-theory model (MTM) of health behavior change interventions in the context of planning substance use prevention and treatment. The current area of intervention programs aimed at preventing and treating substance use may benefit from MTM, an innovative fourth-generation behavior change model. Tobacco, alcohol, and other drugs have all been the subjects of experimental, cross-sectional, and qualitative research. We have presented that additional research is required to compare MTM with knowledge-based therapies or interventions grounded in other theories. A gold standard would be the randomized controlled trials and behavioral change interventions particularly useful for this purpose. In addition, research evaluating the interventions' efficacy must be carefully planned and executed.

Ecological restoration at pilot-scale employing site-specific rationales for small-patch degraded mangroves in Indian Sundarbans.

To date, degraded mangrove ecosystem restoration accomplished worldwide primarily aligns towards rehabilitation with monotypic plantations, while ecological restoration principles are rarely followed in these interventions. However, researchers admit that most of these initiatives' success rate is not appreciable often. An integrative framework of ecological restoration for degraded mangroves where site-specific observations could be scientifically rationalized, with co-located reference pristine mangroves as the target ecosystem to achieve is currently distinctively lacking. Through this experimental scale study, we studied the suitability of site-specific strategies to ecologically restore degraded mangrove patches vis-à-vis the conventional mono-species plantations in a highly vulnerable mangrove ecosystem in Indian Sundarbans. This comprehensive restoration framework was trialed in small discrete degraded mangrove patches spanning ~ 65 ha. Site-specific key restoration components applied are statistically validated through RDA analyses and Bayesian t-tests. 25 quantifiable metrics evaluate the restoration success of a ~ 3 ha degraded mangrove patch with Ridgeline distribution, Kolmogorov-Smirnov (K-S) tests, and Mahalanobis Distance (D2) measure to prove the site's near-equivalence to pristine reference in multiple ecosystem attributes. This restoration intervention irrevocably establishes the greater potential of this framework in the recovery of ecosystem functions and self-sustenance compared to that of predominant monoculture practices for vulnerable mangroves.

COVID-19 Vaccine Acceptance Behavior among Hispanics/Latinxs in Nevada: A Theory-Based Analysis.

Hesitancy toward the COVID-19 vaccine has hindered its rapid uptake among the Hispanic and Latinx populations. The study aimed to use the Multi-Theory Model (MTM) for health behavior change to explain the intention of initiating and sustaining the behavior of COVID-19 vaccination among the Hispanic and Latinx populations that expressed and did not express hesitancy towards the vaccine in Nevada. Using a quantitative cross-sectional and survey-based research study design, data were collected using a 50-item questionnaire and analyzed using multiple linear regression modeling. Of 231 respondents, participatory dialogue (b = 0.113, p < 0.001; b = 0.072, p < 0.001) and behavioral confidence (b = 0.358, p < 0.001; b = 0.206, p < 0.001) displayed significant associations with the initiation of COVID-19 vaccine acceptance among vaccine-hesitant and non-vaccine-hesitant individuals. Emotional transformation (b = 0.087, p < 0.001; b = 0.177, p < 0.001) displayed a significant association with the sustenance of COVID-19 vaccine acceptance among vaccine-hesitant and non-vaccine-hesitant individuals. Results from this study provide evidence that the MTM is a useful tool in predicting COVID-19 vaccine acceptance behavior among Hispanics and Latinxs in Nevada, and it should be used in intervention designs and messaging to promote vaccine uptake.

The relational effects of perceived organizational support, fear of COVID-19, and work-related stress on the safety performance of healthcare workers.

This paper assesses the relational effects of perceived organizational support (POS), fear of COVID-19 (FOC-19), and work-related stress (WRS) on the safety performance of healthcare staff. The sample for this research was extracted from the University College Hospital (UCH) in the Oyo State of Nigeria. The participants were midwives, doctors, auxiliary services staff, and nurses who functioned in a COVID-19 hospital ward, fever or respiratory ICU, Auxiliary services, or outpatient clinics. This investigation espoused a clinical cross-sectional survey involving self-reported surveys. Of the 150 questionnaires distributed, 147 were fit for scrutiny and analyzed with Statistical Packages for the Social Sciences (SPSS version 28). This paper established a relationship between POS and safety performance (SP). Besides, it showed a significant positive correlation between FOC-19 and SP. It further noted that work-related stress negatively relates to safety performance. Moreover, this study showed the significant joint strong influence of POC, FOC-19, and WRS on the safety performance of healthcare workers. Hence, healthcare institutions are encouraged to create adequate support for healthcare workers, particularly during a global health crisis. Government and healthcare institutions should also develop an awareness program on the danger and consequences of getting infected by the virus or infecting other significant others. This will increase the fear of COVID-19 and, consequently, health workers' safety performance. Besides, it is recommended that the management of healthcare institutions provides a proper work structure and schedule to help reduce workloads, consequently reducing WRS, as lowering it improves healthcare workers' safety performance.

Mapping the vulnerability of indigenous fruit trees to environmental change in the fragile savannah ecological zone of Northern Ghana.

Following the incidence of environmental change globally and its negative consequences on livelihoods of local populations, vulnerability assessment has become central to mitigation and adaptation response in the global south. However, researches on vulnerability to climate change in the African continent have seldom focused on Indigenous Fruit Trees (IFTs) although they are an essential part of the strategic forest resources and livelihood systems of local communities. This paper explores the vulnerability of two IFTs, shea (Vitellaria paradoxa) and dawadawa (Parkia biglobosa) to climatic and other stressors that are not directly linked to climate change in rural Ghana and the implications for planning. The paper analyzed vulnerability from farmer perspectives elicited through a mixed study design involving the use of Participatory Rural Appraisal (PRA) methods and a household survey. The results reveal that IFTs are highly vulnerable to drought, rainstorms, bushfires and charcoal production and less vulnerable to heavy precipitation, flash floods and sand mining. Such vulnerability arising from the combined effects of multiple stressors has led to a decreasing trend in production and yields of IFTS over the past few decades, adversely affecting livelihoods of rural women and households. To reduce vulnerability, it is an imperative to promote Environmental Change Adaptation Planning (ECAP) that prioritizes conservation and propagation of IFTs, and diversification of rural livelihoods.

Explaining Screen-Time Behavior Among Preschoolers in Northern India Using Multi Theory Model: A Parental Cross-Sectional Survey.

BACKGROUND: Screen-time (ST) is the time spent on digital media. The American Academy of Pediatrics recommends the daily ST of less than an hour for preschoolers. However, increased ST among preschoolers is becoming a public health concern. OBJECTIVE: This study assessed the multi-theory model (MTM)'s applicability in explaining the ST behavior change among preschoolers through parents. METHODS: A quota sample of 72 parents was drawn from Northern India. Data were analyzed using multiple regression. RESULTS: Behavioral confidence (p < 0.001) and changes in the physical environment (p < 0.001) significantly predicted the initiation of reducing ST. The sustenance of limiting ST was significantly predicted by the emotional transformation (p < 0.001), practice for change (p < 0.001), and changes in the social environment (p = 0.001). CONCLUSIONS: The study highlights the usability of the MTM model in designing and testing interventions for parents to limit ST among their children.

Modeling predictors of COVID-19 health behaviour adoption, sustenance and discontinuation among social media users in Nigeria.

The aim of this study was to suggest a model that explains the predictors of COVID-19 health behaviour adoption, sustenance and discontinuation among social media users in Nigeria. Survey research design was used for the study. The sample size was made of 600 social media users with questionnaire as the instrument for data collection. The structural equation modeling (SEM) was utilized to analyse the result for the study. It was found that six variables-risk vulnerability, risk severity, barriers to action, benefits of action, self-efficacy, and cue to behaviour-predict COVID-19 health behaviour adoption. Also, two variables-risk vulnerability and risk severity-predict COVID-19 health behaviour sustenance. Finally, two variables-behaviour fatigue and behaviour discomfort-predict COVID-19 health behaviour discontinuation. The result of the current study has provided information that could guide health experts in dealing with the issue of behaviour fatigue and behaviour discomfort, which have been identified as responsible for health behaviour discontinuation. In addition, a model for predicting health behaviour adoption, sustenance and discontinuation has been suggested.

Aggregatibacter actinomycetemcomitans (Aa) Under the Radar: Myths and Misunderstandings of Aa and Its Role in Aggressive Periodontitis.

Aggregatibacter actinomycetemcomitans (Aa) is a low-abundance Gram-negative oral pathobiont that is highly associated with a silent but aggressive orphan disease that results in periodontitis and tooth loss in adolescents of African heritage. For the most part Aa conducts its business by utilizing strategies allowing it to conceal itself below the radar of the host mucosal immune defense system. A great deal of misinformation has been conveyed with respect to Aa biology in health and disease. The purpose of this review is to present misconceptions about Aa and the strategies that it uses to colonize, survive, and evade the host. In the process Aa manages to undermine host mucosal defenses and contribute to disease initiation. This review will present clinical observational, molecular, and interventional studies that illustrate genetic, phenotypic, and biogeographical tactics that have been recently clarified and demonstrate how Aa survives and suppresses host mucosal defenses to take part in disease pathogenesis. At one point in time Aa was considered to be the causative agent of Localized Aggressive Periodontitis. Currently, it is most accurate to look at Aa as a community activist and necessary partner of a pathogenic consortium that suppresses the initial host response so as to encourage overgrowth of its partners. The data for Aa's activist role stems from molecular genetic studies complemented by experimental animal investigations that demonstrate how Aa establishes a habitat (housing), nutritional sustenance in that habitat (food), and biogeographical mobilization and/or relocation from its initial habitat (transportation). In this manner Aa can transfer to a protected but vulnerable domain (pocket or sulcus) where its community activism is most useful. Aa's "strategy" includes obtaining housing, food, and transportation at no cost to its partners challenging the economic theory that "there ain't no such thing as a free lunch." This "strategy" illustrates how co-evolution can promote Aa's survival, on one hand, and overgrowth of community members, on the other, which can result in local host dysbiosis and susceptibility to infection.