Eighth Annual Conference of inVIVO Planetary Health: From Challenges to Opportunities

inVIVO Planetary Health (inVIVO) is a progressive scientific movement providing evidence, advocacy, and inspiration to align the interests and vitality of people, place, and planet. Our goal is to transform personal and planetary health through awareness, attitudes, and actions, and a deeper understanding of how all systems are interconnected and interdependent. Here, we present the abstracts and proceedings of our 8th annual conference, held in Detroit, Michigan in May 2019, themed “From Challenges, to Opportunities”. Our far-ranging discussions addressed the complex interdependent ecological challenges of advancing global urbanization, including the biopsychosocial interactions in our living environment on physical, mental, and spiritual wellbeing, together with the wider community and societal factors that govern these. We had a strong solutions focus, with diverse strategies spanning from urban-greening and renewal, nature-relatedness, nutritional ecology, planetary diets, and microbiome rewilding, through to initiatives for promoting resilience, positive emotional assets, traditional cultural narratives, creativity, art projects for personal and community health, and exploring ways of positively shifting mindsets and value systems. Our cross-sectoral agenda underscored the importance and global impact of local initiatives everywhere by contributing to new normative values as part of a global interconnected grass-roots movement for planetary health

Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts

The Case for Visual Analytics of Arsenic Concentrations in Foods

Arsenic is a naturally occurring toxic metal and its presence in food could be a potential risk to the health of both humans and animals. Prolonged ingestion of arsenic contaminated water may result in manifestations of toxicity in all systems of the body. Visual Analytics is a multidisciplinary field that is defined as the science of analytical reasoning facilitated by interactive visual interfaces. The concentrations of arsenic vary in foods making it impractical and impossible to provide regulatory limit for each food. This review article presents a case for the use of visual analytics approaches to provide comparative assessment of arsenic in various foods. The topics covered include (i) metabolism of arsenic in the human body; (ii) arsenic concentrations in various foods; (ii) factors affecting arsenic uptake in plants; (ii) introduction to visual analytics; and (iv) benefits of visual analytics for comparative assessment of arsenic concentration in foods. Visual analytics can provide an information superstructure of arsenic in various foods to permit insightful comparative risk assessment of the diverse and continually expanding data on arsenic in food groups in the context of country of study or origin, year of study, method of analysis and arsenic species

The Canadian Urban Environmental Health Research Consortium - A protocol for building a national environmental exposure data platform for integrated analyses of urban form and health

Background: Multiple external environmental exposures related to residential location and urban form including, air pollutants, noise, greenness, and walkability have been linked to health impacts or benefits. The Canadian Urban Environmental Health Research Consortium (CANUE) was established to facilitate the linkage of extensive geospatial exposure data to existing Canadian cohorts and administrative health data holdings. We hypothesize that this linkage will enable investigators to test a variety of their own hypotheses related to the interdependent associations of built environment features with diverse health outcomes encompassed by the cohorts and administrative data. Methods: We developed a protocol for compiling measures of built environment features that quantify exposure; vary spatially on the urban and suburban scale; and can be modified through changes in policy or individual behaviour to benefit health. These measures fall into six domains: air quality, noise, greenness, weather/climate, and transportation and neighbourhood factors; and will be indexed to six-digit postal codes to facilitate merging with health databases. Initial efforts focus on existing data and include estimates of air pollutants, greenness, temperature extremes, and neighbourhood walkability and socioeconomic characteristics. Key gaps will be addressed for noise exposure, with a new national model being developed, and for transportation-related exposures, with detailed estimates of truck volumes and diesel emissions now underway in selected cities. Improvements to existing exposure estimates are planned, primarily by increasing temporal and/or spatial resolution given new satellite-based sensors and more detailed national air quality modelling. Novel metrics are also planned for walkability and food environments, green space access and function and life-long climate-related exposures based on local climate zones. Critical challenges exist, for example, the quantity and quality of input data to many of the models and metrics has changed over time, making it difficult to develop and validate historical exposures. Discussion: CANUE represents a unique effort to coordinate and leverage substantial research investments and will enable a more focused effort on filling gaps in exposure information, improving the range of exposures quantified, their precision and mechanistic relevance to health. Epidemiological studies may be better able to explore the common theme of urban form and health in an integrated manner, ultimately contributing new knowledge informing policies that enhance healthy urban living

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Knowledge Visualizations to Inform Decision Making for Improving Food Accessibility and Reducing Obesity Rates in the United States

The aim of this article is to promote the use of knowledge visualization frameworks in the creation and transfer of complex public health knowledge. The accessibility to healthy food items is an example of complex public health knowledge. The United States Department of Agriculture Food Access Research Atlas (FARA) dataset contains 147 variables for 72,864 census tracts and includes 16 food accessibility variables with binary values (0 or 1). Using four-digit and 16-digit binary patterns, we have developed data analytical procedures to group the 72,684 U.S. census tracts into eight and forty groups respectively. This value-added FARA dataset facilitated the design and production of interactive knowledge visualizations that have a collective purpose of knowledge transfer and specific functions including new insights on food accessibility and obesity rates in the United States. The knowledge visualizations of the binary patterns could serve as an integrated explanation and prediction system to help answer why and what-if questions on food accessibility, nutritional inequality and nutrition therapy for diabetic care at varying geographic units. In conclusion, the approach of knowledge visualizations could inform coordinated multi-level decision making for improving food accessibility and reducing chronic diseases in locations defined by patterns of food access measures

Bioinformatics Investigations of Universal Stress Proteins from Mercury-Methylating Desulfovibrionaceae

The presence of methylmercury in aquatic environments and marine food sources is of global concern. The chemical reaction for the addition of a methyl group to inorganic mercury occurs in diverse bacterial taxonomic groups including the Gram-negative, sulfate-reducing Desulfovibrionaceae family that inhabit extreme aquatic environments. The availability of whole-genome sequence datasets for members of the Desulfovibrionaceae presents opportunities to understand the microbial mechanisms that contribute to methylmercury production in extreme aquatic environments. We have applied bioinformatics resources and developed visual analytics resources to categorize a collection of 719 putative universal stress protein (USP) sequences predicted from 93 genomes of Desulfovibrionaceae. We have focused our bioinformatics investigations on protein sequence analytics by developing interactive visualizations to categorize Desulfovibrionaceae universal stress proteins by protein domain composition and functionally important amino acids. We identified 651 Desulfovibrionaceae universal stress protein sequences, of which 488 sequences had only one USP domain and 163 had two USP domains. The 488 single USP domain sequences were further categorized into 340 sequences with ATP-binding motif and 148 sequences without ATP-binding motif. The 163 double USP domain sequences were categorized into (1) both USP domains with ATP-binding motif (3 sequences); (2) both USP domains without ATP-binding motif (138 sequences); and (3) one USP domain with ATP-binding motif (21 sequences). We developed visual analytics resources to facilitate the investigation of these categories of datasets in the presence or absence of the mercury-methylating gene pair (hgcAB). Future research could utilize these functional categories to investigate the participation of universal stress proteins in the bacterial cellular uptake of inorganic mercury and methylmercury production, especially in anaerobic aquatic environments

Knowledge Building Insights on Biomarkers of Arsenic Toxicity to Keratinocytes and Melanocytes

Exposure to inorganic arsenic induces skin cancer and abnormal pigmentation in susceptible humans. High-throughput gene transcription assays such as DNA microarrays allow for the identification of biological pathways affected by arsenic that lead to initiation and progression of skin cancer and abnormal pigmentation. The overall purpose of the reported research was to determine knowledge building insights on biomarker genes for arsenic toxicity to human epidermal cells by integrating a collection of gene lists annotated with biological information. The information sets included toxicogenomics gene-chemical interaction; enzymes encoded in the human genome; enriched biological information associated with genes; environmentally relevant gene sequence variation; and effects of non-synonymous single nucleotide polymorphisms (SNPs) on protein function. Molecular network construction for arsenic upregulated genes TNFSF18 (tumor necrosis factor [ligand] superfamily member 18) and IL1R2 (interleukin 1 Receptor, type 2) revealed subnetwork interconnections to E2F4 , an oncogenic transcription factor, predominantly expressed at the onset of keratinocyte differentiation. Visual analytics integration of gene information sources helped identify RAC1, a GTP binding protein, and TFRC, an iron uptake protein as prioritized arsenic-perturbed protein targets for biological processes leading to skin hyperpigmentation. RAC1 regulates the formation of dendrites that transfer melanin from melanocytes to neighboring keratinocytes. Increased melanocyte den-dricity is correlated with hyperpigmentation. TFRC is a key determinant of the amount and location of iron in the epidermis. Aberrant TFRC expression could impair cutaneous iron metabolism leading to abnormal pigmentation seen in some humans exposed to arsenicals. The reported findings contribute to insights on how arsenic could impair the function of genes and biological pathways in epidermal cells. Finally, we developed visual analytics resources to facilitate further exploration of the information and knowledge building insights on arsenic toxicity to human epidermal keratinocytes and melanocytes