Review of Pseudoloma neurophilia (Microsporidia): A common neural parasite of laboratory zebrafish (Danio rerio).

Zebrafish (Danio rerio) is now the second most used animal model in biomedical research. As with other vertebrate models, underlying diseases and infections often impact research. Beyond mortality and morbidity, these conditions can compromise research end points by producing nonprotocol induced variation within experiments. Pseudoloma neurophilia, a microsporidium that targets the central nervous system, is the most frequently diagnosed pathogen in zebrafish facilities. The parasite undergoes direct, horizontal transmission within populations, and is also maternally transmitted with spores in ovarian fluid and occasionally within eggs. This transmission explains the wide distribution among research laboratories as new lines are generally introduced as embryos. The infection is chronic, and fish apparently never recover following the initial infection. However, most fish do not exhibit outward clinical signs. Histologically, the parasite occurs as aggregates of spores throughout the midbrain and spinal cord and extends to nerve roots. It often elicits meninxitis, myositis, and myodegeneration when it infects the muscle. There are currently no described therapies for the parasite, thus the infection is best avoided by screening with PCR-based tests and removal of infected fish from a facility. Examples of research impacts include reduced fecundity, behavioral changes, transcriptome alterations, and autofluorescent lesions.

Suicide Prevention Takes a Nation: Collaborative Approaches to Universalize Suicide Prevention.

Suicide is a complex public health issue impacting many children and adolescents-and their families-each year, and it requires a complex public health solution. Local, state, and national collaboratives that leverage evidence-based strategies, foster community engagement, and prioritize equity are necessary to holistically address this issue. Here, the authors discuss the necessary steps for fostering inclusive community partnerships and outline the rationale for partnering with schools, youth groups, faith organizations, parent-teacher organizations, clinical settings, and professional organizations, as well as collaborating with the juvenile justice and child welfare systems and working together to foster suicide prevention policy.

Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database.

BACKGROUND: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. PATIENTS AND METHODS: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care® protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. RESULTS: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were in VHL (126, 42.6%), PBRM1 (102, 34.5%), and SETD2 (54, 18.2%). BAP1 had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14, p = 0.056) or multivariable (OR 0.15, p = 0.067) analysis. Median OS was not reached in either cohort. CONCLUSIONS: Using the clinicogenomic ORIEN database, our study found lower rates of BAP1 mutations in RCC specimens from patients with ACKD, which may reflect a BAP1-independent mutational driver of RCC in patients with ACKD.

Neoadjuvant Cisplatin-based Chemotherapy in Nonmetastatic Muscle-invasive Bladder Cancer: A Systematic Review and Pooled Meta-analysis to Determine the Preferred Regimen.

OBJECTIVE: To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity. MATERIALS AND METHODS: This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively. RESULTS: Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies. CONCLUSION: Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.

Power imbalances and equity in the day-to-day functioning of a north plus multi-south higher education institutions partnership: a case study.

BACKGROUND: Partnerships between Higher Education Institutions (HEIs) in the global north and south have commonly been used as a vehicle to drive global health research and initiatives. Among these initiatives, include health system strengthening, research capacity building, and human resource training in developing countries. However, the partnership functioning of many global north-south partnerships still carry legacies of colonialism through unrecognized behavior patterns, attitudes, and belief systems in how they function. Even with research literature calling for a shift from equality to equity in the functioning of these partnerships, many still struggle with issues of complex and unspoken power dynamics. To understand the successes and challenges of north-south partnerships, this paper explored partnership development and functioning of a northern and multi-southern HEIs partnership focused on nutrition education and research. METHODS: A qualitative research approach was used; data were collected through in-depth interviews (IDIs) with questions developed from the Bergen Model of Collective Functioning (BMCF). Thirteen IDIs were conducted with partners from all institutions including stakeholders. FINDINGS: The partnership was built on the foundation of experiences and lessons of a previous partnership. Partners used these experiences and lessons to devise strategies to improve partnership inputs, communication, leadership, roles and structures, and maintenance and communication tasks. However, these strategies had an impact on partnership functioning giving rise to issues of inequitable power dynamics. The northern partner had two roles: one as an equal partner and another as distributor of project funds; this caused a conflict in roles for this partner. The partners distinguished themselves according to partner resources - two partners were named implementing partners and two named supportive partners. Roles and partner resources were the greatest contributors to power imbalances and caused delays in project activities. CONCLUSION: Using the BMCF to examine partnership dynamics illuminated that power imbalances caused a hierarchical stance in the partnership with northern partners having overall control and power of decision-making in the partnership. This could impact the effectiveness and sustainability of project in the southern institutions going forward.

Deficiency in homologous recombination is associated with changes in cell cycling and morphology in Saccharomyces cerevisiae.

Exposure of eukaryotic cells to ionizing radiation or clastogenic chemicals leads to formation of DNA double-strand breaks (DSBs). These lesions are also generated internally by chemicals and enzymes, in the absence of exogenous agents, though the sources and consequences of such endogenously generated DSBs remain poorly understood. In the current study, we have investigated the impact of reduced recombinational repair of endogenous DSBs on stress responses, cell morphology and other physical properties of S. cerevisiae (budding yeast) cells. Use of phase contrast and DAPI-based fluorescence microscopy combined with FACS analysis confirmed that recombination-deficient rad52 cell cultures exhibit chronically high levels of G2 phase cells. Cell cycle phase transit times during G1, S and M were similar in WT and rad52 cells, but the length of G2 phase was increased by three-fold in the mutants. rad52 cells were larger than WT in all phases of the cycle and displayed other quantifiable changes in physical characteristics. The high G2 cell phenotype was abolished when DNA damage checkpoint genes, but not spindle assembly checkpoint genes, were co-inactivated with RAD52. Several other RAD52 group mutants (rad51, rad54, rad55, rad57 and rad59) also exhibited the high G2 cell phenotype. The results indicate that recombination deficiency leads to accumulation of unrepaired DSBs during normal mitotic growth that activate a major stress response and produce distinct changes in cellular physiology and morphology.

Developing the Blueprint for Youth Suicide Prevention.

Suicide and suicidal behavior among youth and young adults are a major public health crisis, exacerbated by the COVID-19 pandemic and demonstrated by increases in suicidal ideation and attempts among youth. Supports are needed to identify youth at risk and intervene in safe and effective ways. To address this need, the American Academy of Pediatrics and the American Foundation for Suicide Prevention, in collaboration with experts from the National Institute of Mental Health, developed the Blueprint for Youth Suicide Prevention ( Blueprint ) to translate research into strategies that are feasible, pragmatic, and actionable across all contexts in which youth live, learn, work, and play. In this piece, we describe the process of developing and disseminating the Blueprint. Through a summit and focus meetings, cross-sectoral partners convened to discuss the context of suicide risk among youth; explore the landscape of science, practice, and policy; build partnerships; and identify strategies for clinics, communities, and schools-all with a focus on health disparities and equity. These meetings resulted in 5 major takeaways: (1) suicide is often preventable; (2) health equity is critical to suicide prevention; (3) individual and systems changes are needed; (4) resilience should be a key focus; and (5) cross-sectoral partnerships are critical. These meetings and takeaways then informed the content of the Blueprint , which discusses the epidemiology of youth and young adult suicide and suicide risk, including health disparities; the importance of a public health framework; risk factors, protective factors, and warning signs; strategies for clinical settings, strategies for community and school settings; and policy priorities. Following the process description, lessons learned are also discussed, followed by a call to action for the public health community and all who serve and support youth. Finally, key steps to establishing and sustaining partnerships and implications for policy and practice are discussed.

Outcomes of Second-Line Therapies in Patients With Metastatic de Novo and Treatment-Emergent Neuroendocrine Prostate Cancer: A Multi-Institutional Study.

BACKGROUND: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. PATIENTS AND METHODS: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. RESULTS: Fifty-eight patients (32 de novo NEPC, 26 T-NEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). CONCLUSIONS: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice.

Spontaneous resolution of traumatic bronchial tear after thoracic crush injury.

Traumatic bronchial tears are rare life-threatening injuries. Here, we report a 28-year old male who presented after sustaining a crush injury to his thoracic cavity, resulting in a spiral left mainstem bronchial tear secondary to high intraluminal pressure. While preparing for surgery, a preoperative bronchoscopy found that the bronchial tear had re-approximated and effectively sealed the laceration. No operative intervention was performed and the patient subsequently underwent a full recovery. While most bronchial tears undergo surgical intervention, our report describes the successful management of a bronchial tear injury with a non-operative approach and supportive care.

Early detection of Pseudocapillaria tomentosa by qPCR in four lines of zebrafish, Danio rerio (Hamilton 1882).

The intestinal nematode Pseudocapillaria tomentosa in zebrafish (Danio rerio) causes profound intestinal lesions, emaciation and death and is a promoter of a common intestinal cancer in zebrafish. This nematode has been detected in zebrafish from about 15% of the laboratories. Adult worms are readily detected about 3 weeks after exposure by either histology or wet mount preparations of the intestine, and larval worms are inconsistently observed in fish before this time. A quantitative PCR (qPCR) test was recently developed to detect the worm in fish and water, and here we determined that the test on zebrafish intestines was effective for earlier detection. Four lines of zebrafish (AB, TU, 5D and Casper) were experimentally infected and evaluated by wet mounts and qPCR at 8, 15-, 22-, 31- and 44-day post-exposure (dpe). At the first two time points, only 8% of the wet mounts from exposed fish were identified as infected, while the same intestines screened by qPCR showed 78% positivity, with low and consistent cycle threshold (Ct) values at these times. Wet mounts at later time points showed a high prevalence of infection, but this was still surpassed by qPCR.

Development and Validation of an Electronic Health Record-based Score for Triage to Perioperative Medicine.

OBJECTIVE: To develop an electronic health record-based risk model for perioperative medicine (POM) triage and compare this model with legacy triage practices that were based on clinician assessment. SUMMARY OF BACKGROUND DATA: POM clinicians seek to address the increasingly complex medical needs of patients prior to scheduled surgery. Identifying which patients might derive the most benefit from evaluation is challenging. METHODS: Elective surgical cases performed within a health system 2014- 2019 (N = 470,727) were used to develop a predictive score, called the Comorbidity Assessment for Surgical Triage (CAST) score, using split validation. CAST incorporates patient and surgical case characteristics to predict the risk of 30-day post-operative morbidity, defined as a composite of mortality and major NSQIP complications. Thresholds of CAST were then selected to define risk groups, which correspond with triage to POM appointments of different durations and modalities. The predictive discrimination CAST score was compared with the surgeon's assessments of patient complexity and the American Society of Anesthesiologists class. RESULTS: The CAST score demonstrated a significantly higher discrimination for predicting post-operative morbidity (area under the receiver operating characteristic curve 0.75) than the surgeon's complexity designation (0.63; P < 0.001) or the American Society of Anesthesiologists (0.65; P < 0.001) ( Fig. 1 ). Incorporating the complexity designation in the CAST model did not significantly alter the discrimination (0.75; P = 0.098). Compared with the complexity designation, classification based on CAST score groups resulted a net reclassification improvement index of 10.4% ( P < 0.001) ( Table 1 ). CONCLUSION: A parsimonious electronic health record-based predictive model demonstrates improved performance for identifying pre-surgical patients who are at risk than previously-used assessments for POM triage.

Effectiveness and durability of benefit of mTOR inhibitors in a real-world cohort of patients with metastatic prostate cancer and PI3K pathway alterations.

BACKGROUND: Alterations in the PTEN/PI3K/AKT/mTOR pathway are prevalent in prostate cancer. In this retrospective study, we evaluated the clinical effectiveness of mTOR inhibitors (mTORi) in patients with metastatic prostate cancer (mPCA) and tissue assessed phosphatidyl-3-inositol kinase (PI3K) pathway alterations. METHODS: This study used a nationwide (US-based) de-identified PCA clinico-genomic database, originating from approximately 280 US cancer clinics (~800 sites of care). We evaluated treatment data for patients with PCA from October 2014 to February 2020. In a cohort of 2301 PCA patients with 7208 evaluable treatment lines, we selected 17 mPCA patients (2 hormone-sensitive, 15 castrate-resistant) with tissue assessed PI3K pathway alterations by comprehensive genomic profiling who received mTORi treatment. RESULTS: Patients had a median age of 72 years (IQR 68.0, 76.0) and were heavily pretreated with a median 3 lines of therapy prior to mTORi use (range 0-6). The PI3K pathway alterations included PTENdel (10 patients, 58.8%), AKT1mut (4 patients, 23.5%), PTENmut (2 patients, 11.8%), and dual PTENmut and PIK3CAmut (1 patient, 5.9%). Most (15 patients, 88.2%) were treated with everolimus monotherapy. Among 10 patients with on treatment PSA available, 2 patients had a PSA decrease ≥10% at week 12 and 5 patients overall had a subsequent PSA decrease. For those on mTORi, the median time to next treatment was 3.62 months (range 0, 8.52). CONCLUSIONS: In this small cohort of mPCA patients with tissue assessed PI3K pathway alterations, mTORi therapy was not effective with few PSA responses and short duration of therapy.

Application of an eDNA assay for the detection of Pseudoloma neurophilia (Microsporidia) in zebrafish (Danio rerio) facilities.

Environmental DNA (eDNA) water assays are beginning to be implemented for many important pathogens in confined aquaculture systems. Recirculating systems are rapidly being developed for fin fish aquaculture. Zebrafish (Danio rerio) are reared in these systems, and Pseudoloma neurophilia (Microsporidia) represents a serious challenge for zebrafish research facilities. Diagnosis of the pathogen has traditionally used histology or PCR of tissues with lethal sampling. However, with the development of a nonlethal assay to detect P. neurophilia in tank water, facilities will be able to integrate the assay into routine surveillance efforts to couple with their established protocols. Here, we first describe a modified protocol to extract and quantify parasite DNA from the environment for nonlethal detection of P. neurophilia in adult zebrafish populations. Using this modified assay, we then evaluated water samples from a longitudinal experimental infection study, targeting timepoints during initial infection. The parasite was detectable in the water immediately after initial exposure until week 4 post exposure (pe), when the parasite was undetectable until 7 weeks pe. After that time, the parasite was sporadically detected in the water for the 10-month study, likely correlating with the lifecycle of the parasite. Using water samples from the Zebrafish International Resource Center, we also validated the clinical relevance of the assay in a large zebrafish facility. The integration of this assay at ZIRC will significantly compliment surveillance and control efforts for the microsporidian parasite.

MULTI-STATE OCCUPANCY MODEL ESTIMATES PROBABILITY OF DETECTION OF AN AQUATIC PARASITE USING ENVIRONMENTAL DNA: PSEUDOLOMA NEUROPHILIA IN ZEBRAFISH AQUARIA.

Detecting the presence of important parasites within a host and its environment is critical to understanding the dynamics that influence a pathogen's ability to persist, while accurate detection is also essential for the implementation of effective control strategies. Pseudoloma neurophilia is the most common pathogen reported in zebrafish (Danio rerio) research facilities. The only assays currently available for P. neurophilia are through lethal sampling, often requiring euthanasia of the entire population for accurate estimates of prevalence in small populations. We present a non-lethal screening method to detect P. neurophilia in tank water based on the detection of environmental DNA (eDNA) from this microsporidium, using a previously developed qPCR assay that was adapted to the digital PCR (dPCR) platform to complement current surveillance protocols. Using the generated dPCR data, a multi-state occupancy model was also implemented to predict the probability of detecting the microsporidium in tank water under different flow regimes and pathogen prevalence. The occupancy model revealed that samples collected in static conditions were more informative than samples collected from flow-through conditions, with a probability of detection at 80% and 47%, respectively. There was also a positive correlation between the frequency of detection in water and prevalence in fish based on qPCR.

Structural indicators of suicide: an exploration of state-level risk factors among Black and White people in the United States, 2015-2019.

Purpose ­: Death by suicide among Black people in the USA have increased by 35.6% within the past decade. Among youth under the age of 24 years old, death by suicide among Black youth have risen substantially. Researchers have found that structural inequities (e.g. educational attainment) and state-specific variables (e.g. minimum wage, incarceration rates) may increase risk for suicide among Black people compared to White people in the USA. Given the limited understanding of how such factors systematically affect Black and White communities differently, this paper aims to examine these relationships across US states using publicly available data from 2015 to 2019. Design/methodology/approach ­: Data were aggregated from various national sources including the National Center for Education Statistics, the Department of Labor, the FBI's Crime in the US Reports and the Census Bureau. Four generalized estimating equations (GEE) models were used to examine the impact of state-level variables on suicide rates: Black adults suicide rate, Black youth (24 years and younger) suicide rate, White adult suicide rate and White youth suicide rate. Each model includes state-level hate group rates, minimum wage, violent crime rates, gross vacancy rates, and race-specific state-level poverty rates, incarceration rates and graduation rates. Findings ­: Across all GEE models, suicide rates rose between 2015-2019 (ß = 1.11 - 2.78; ß = 0.91 - 1.82; ß = 0.52 - 3.09; ß = 0.16 - 1.53). For the Black adult suicide rate, state rates increased as the proportion of Black incarceration rose (ß = 1.14) but fell as the gross housing vacancy rates increased (ß = -1.52). Among Black youth, state suicide rates rose as Black incarcerations increased (ß = 0.93). For the adult White suicide rate, state rates increased as White incarceration (ß = 1.05) and percent uninsured increased (ß = 1.83), but fell as White graduation rates increased (ß = -2.36). Finally, among White youth, state suicide rates increased as the White incarceration rate rose (ß = 0.55) and as the violent crime rate rose (ß = 0.55) but decreased as state minimum wages (ß = -0.61), White poverty rates (ß = -0.40) and graduation rates increased (ß = -0.97). Originality/value ­: This work underscores how structural factors are associated with suicide rates, and how such factors differentially impact White and Black communities.

Progression of infection and detection of Pseudoloma neurophilia in zebrafish Danio rerio Hamilton by PCR and histology.

Pseudoloma neurophilia is a critical threat to the zebrafish (Danio rerio) model, as it is the most common infectious agent found in research facilities. In this study, our objectives were two-fold: (1) compare the application of diagnostic tools for P. neurophilia and (2) track the progression of infection using PCR and histology. The first experiment showed that whole-body analysis by qPCR (WB-qPCR) can be a standardized process, providing a streamlined diagnostic protocol, without the need for extraction of specific tissues. Evaluating the course of infection in experimentally infected fish, we showed key dynamics in infection. Starting with a low dose exposure of 8000 spores/fish, the prevalence remained low until 92 days post-exposure (dpe), followed by a 30%-40% prevalence by histology or 40%-90% by PCR until the end of the experiment at 334 dpe. WB-qPCR positively detected infection in more fish than histology throughout the study, as WB-qPCR detected the parasite as early as 4 dpe, whereas it was undetected by histology until 92 dpe. We also added a second slide for histologic analyses, showing an increase in detection rate from 24% to 26% when we combined all data from our experiments, but this increase was not statistically significant.

Recent Advances with Fish Microsporidia.

There have been several significant new findings regarding Microsporidia of fishes over the last decade. Here we provide an update on new taxa, new hosts and new diseases in captive and wild fishes since 2013. The importance of microsporidiosis continues to increase with the rapid growth of finfish aquaculture and the dramatic increase in the use of zebrafish as a model in biomedical research. In addition to reviewing new taxa and microsporidian diseases, we include discussions on advances with diagnostic methods, impacts of microsporidia on fish beyond morbidity and mortality, novel findings with transmission and invertebrate hosts, and a summary of the phylogenetics of fish microsporidia.

Expanding our paradigms: Intersectional and socioecological approaches to suicide prevention.

Despite increasing research on suicide, we continue to see rising rates, particularly among youth. In answering recent calls for critical suicidology and transdisciplinary approaches to research, I discuss expanding beyond the paradigmatic confines of suicidology by proposing two related approaches to improve our science: intersectionality theory and socioecological theory. Following a discussion of social identity and its relation to suicide risk, I review the literature on these topics and highlight importance of paying attention to the unique experiences of youth through the study of intersectionality and using socioecological models in our research moving forward.

Wellbeing as a policy framework for health promotion and sustainable development.

For years Gross Domestic Product (GDP) has served as a key indicator of human progress and "successful" societies. Unfortunately, GDP has failed to robustly capture the human experience or predict resilience through crises; and obscures the presence of inequity -- a key determinant of suffering. It is clear the global community needs a new organizing principle: one that envisions and measures progress by focusing on the conditions that support health, resilience, and overall wellbeing. This paper examines key health promotion concepts and approaches, juxtaposed with philosophical underpinnings of the concept of wellbeing, alternative measurement strategies, and examples of wellbeing policy initiatives. In doing so, the paper highlights the relevance of wellbeing policy frameworks to health promotion, the utility of health promotion strategies for implementing wellbeing policy frameworks, and controversies and pitfalls that require consideration. The paper concludes by outlining how health promotion is uniquely poised to contribute to wellbeing policy frameworks that promote the sources of human and planetary thriving through sustainable development, and that promoting a wellbeing agenda can strengthen efforts to promote health by addressing social determinants and ensuring universal access to resources that support coping with emerging challenges and strengthen resilience.