Projected changes in heatwaves over Central and South America using high-resolution regional climate simulations.

Heatwaves (HWs) pose a severe threat to human and ecological systems. Here we assess the projected changes in heatwaves over Latin America using bias corrected high-resolution regional climate simulations under two Representative Concentration Pathway scenarios (RCPs). Heatwaves are projected to be more frequent, long-lasting, and intense in the mid-century under both RCP2.6 and RCP8.5 scenarios, with severe increases under the RCP8.5 scenario. Even under the low emissions scenario of RCP2.6, the frequency of heatwaves doubles over most of the region. A three- to tenfold rise in population exposure to heatwave days is projected over Central and South America, with climate change playing a dominant role in driving these changes. Results show that following the low emission pathway would reduce 57% and 50% of heatwave exposure for Central and South American regions respectively, highlighting the need to control anthropogenic emissions and implement sustainable practices.

A comparison of heat effects on road injury frequency between active travelers and motorized transportation users in six tropical and subtropical cities in Taiwan.

Road traffic injuries (RTIs) pose significant public health threats, particularly for vulnerable road users such as pedestrians and cyclists. While recent studies have revealed adverse impacts of heat exposure on RTI frequency among motorized road users, a research gap persists in understanding these impacts on non-motorized road users, especially in tropical regions where their vulnerability can be heightened due to differential thermal exposure, adaptive capacity, and biological sensitivity. In this study, we compared associations between high temperatures and RTIs across four different crash-involved modes of transportation-pedestrians, cyclists, motorcyclists, and car drivers in Taiwan. Leveraging data on RTI records and temperature conditions in Taiwan's six municipalities from 2018 to 2022, we conducted a city-time-stratified case-crossover analysis. We employed distributed lag non-linear models with conditional Poisson regression models to estimate temperature-RTI associations for each mode of transportation, adjusting for various weather factors and unmeasured spatio-temporal patterns. Our findings reveal that individuals using exposed, open transportation modes (i.e., pedestrians, cyclists, and motorcyclists) exhibited higher relative risks of heat-induced RTIs than car drivers, with non-motorized mode users showing greater susceptibility compared to their motorized counterparts. These elevated risks can be attributed to the absence of built-in cooling systems in open travel modes and the increased exertional heat stress implied in active travel. Our study contributes novel insights to a global concern related to climate change, extending its impact to road safety, a health outcome rarely studied in the context of a changing climate. Our findings are thus important, especially for regions where rising temperatures regularly approach or exceed human physiological limits related to heat tolerance in the coming decades. Additionally, our findings hold significance in the existing urban health literature, particularly within the context of the emerging era of micromobility-a category of low-speed, non-enclosed, and lightweight vehicles increasingly integrated into urban activities worldwide.

Research Translation to Promote Urban Health in Latin America: The SALURBAL Experience.

In highly urbanized and unequal Latin America, urban health and health equity research are essential to effective policymaking. To ensure the application of relevant and context-specific evidence to efforts to reduce urban health inequities, urban health research in Latin America must incorporate strategic research translation efforts. Beginning in 2017, the Urban Health in Latin America (SALURBAL) project implemented policy-relevant research and engaged policymakers and the public to support the translation of research findings. Over 6 years, more than 200 researchers across eight countries contributed to SALURBAL's interdisciplinary network. This network allowed SALURBAL to adapt research and engagement activities to local contexts and priorities, thereby maximizing the policy relevance of research findings and their application to promote policy action, inform urban interventions, and drive societal change. SALURBAL achieved significant visibility and credibility among academic and nonacademic urban health stakeholders, resulting in the development of evidence and tools to support urban policymakers, planners, and policy development processes across the region. These efforts and their outcomes reveal important lessons regarding maintaining flexibility and accounting for local context in research, ensuring that resources are dedicated to policy engagement and dissemination activities, and recognizing that assessing policy impact requires a nuanced understanding of complex policymaking processes. These reflections are relevant for promoting urban health and health equity research translation across the global south and worldwide. This paper presents SALURBAL's strategy for dissemination and policy translation, highlights innovative initiatives and their outcomes, discusses lessons learned, and shares recommendations for future efforts to promote effective translation of research findings.

Uncovering physical activity trade-offs in transportation policy: A spatial agent-based model of Bogotá, Colombia.

BACKGROUND: Transportation policies can impact health outcomes while simultaneously promoting social equity and environmental sustainability. We developed an agent-based model (ABM) to simulate the impacts of fare subsidies and congestion taxes on commuter decision-making and travel patterns. We report effects on mode share, travel time and transport-related physical activity (PA), including the variability of effects by socioeconomic strata (SES), and the trade-offs that may need to be considered in the implementation of these policies in a context with high levels of necessity-based physical activity. METHODS: The ABM design was informed by local stakeholder engagement. The demographic and spatial characteristics of the in-silico city, and its residents, were informed by local surveys and empirical studies. We used ridership and travel time data from the 2019 Bogotá Household Travel Survey to calibrate and validate the model by SES. We then explored the impacts of fare subsidy and congestion tax policy scenarios. RESULTS: Our model reproduced commuting patterns observed in Bogotá, including substantial necessity-based walking for transportation. At the city-level, congestion taxes fractionally reduced car use, including among mid-to-high SES groups but not among low SES commuters. Neither travel times nor physical activity levels were impacted at the city level or by SES. Comparatively, fare subsidies promoted city-level public transportation (PT) ridership, particularly under a 'free-fare' scenario, largely through reductions in walking trips. 'Free fare' policies also led to a large reduction in very long walking times and an overall reduction in the commuting-based attainment of physical activity guidelines. Differential effects were observed by SES, with free fares promoting PT ridership primarily among low-and-middle SES groups. These shifts to PT reduced median walking times among all SES groups, particularly low-SES groups. Moreover, the proportion of low-to-mid SES commuters meeting weekly physical activity recommendations decreased under the 'freefare' policy, with no change observed among high-SES groups. CONCLUSIONS: Transport policies can differentially impact SES-level disparities in necessity-based walking and travel times. Understanding these impacts is critical in shaping transportation policies that balance the dual aims of reducing SES-level disparities in travel time (and time poverty) and the promotion of choice-based physical activity.

Shadows over Caribbean reefs: Identification of a new invasive soft coral species, Xenia umbellata, in southwest Puerto Rico.

In October 2023, several colonies of an alien soft coral species were reported on shallow reefs in southwest Puerto Rico. The soft coral was identified as a xeniid octocoral (species undetermined), resembling the octocoral Unomia stolonifera, which has invaded and overgrown reefs in Venezuela in recent years. To conclusively characterize the species of the invading xeniid, we employed multilocus barcoding targeting four genes (ND2, mtMutS, COI, and 28S) of three separate colonies across three locations in southwest Puerto Rico. Sequence comparisons with xeniid sequences from GenBank, including those from the genera Xenia and Unomia, indicated a 100% sequence identity (>3,000 bp combined) with the species Xenia umbellata (Octocorallia : Malacalcyonacea : Xeniidae). Xenia umbellata is native to the Red Sea and to our knowledge, this represents the first confirmed case of this species as an invader on Caribbean reefs. Similar to U. stolonifera, X. umbellata is well known for its ability to rapidly overgrow substrate as well as tolerate environmental extremes. In addition, X. umbellata has recently been proposed as a model system for tissue regeneration having the ability to regenerate completely from a single tentacle. These characteristics greatly amplify X. umbellata's potential to adversely affect any reef it invades. Our findings necessitate continued collaborative action between local management agencies and stakeholders in Puerto Rico, as well as neighboring islands, to monitor and control this invasion prior to significant ecological perturbation.

Short-term associations between fine particulate air pollution and cardiovascular and respiratory mortality in 337 cities in Latin America.

Ambient air pollution is a health concern in Latin America given its large urban population exposed to levels above recommended guidelines. Yet no studies have examined the mortality impact of air pollutants in the region across a wide range of cities. We assessed whether short-term levels of fine particulate matter (PM2.5) from modeled estimates, are associated with cardiovascular and respiratory mortality among adults in 337 cities from 9 Latin American countries. We compiled mortality, PM2.5 and temperature data for the period 2009-2015. For each city, we evaluated the association between monthly changes in PM2.5 and cardiovascular and respiratory mortality for sex and age subgroups using Poisson models, adjusted for seasonality, long-term trend, and temperature. To accommodate possibly different associations of mortality with PM2.5 by age, we included interaction terms between changes in PM2.5 and age in the models. We combined the city-specific estimates using a random effects meta-regression to obtain mortality relative risks for each sex and age group. We analyzed 3,026,861 and 1,222,623 cardiovascular and respiratory deaths, respectively, from a study population that represents 41 % of the total population of Latin America. We observed that a 10 µg/m3 increase in monthly PM2.5 is associated with an increase of 1.3 % (95 % confidence interval [CI], 0.4 to 2.2) in cardiovascular mortality and a 0.9 % increase (95 % CI -0.6 to 2.4) in respiratory mortality. Increases in mortality risk ranged between -0.5 % to 3.0 % across 6 sex-age groups, were larger in men, and demonstrated stronger associations with cardiovascular mortality as age increased. Socioeconomic, environmental and health contexts in Latin America are different than those present in higher income cities from which most evidence on air pollution impacts is drawn. Locally generated evidence constitutes a powerful instrument to engage civil society and help drive actions to mitigate and control ambient air pollution.

Genetic Ancestry-specific Molecular and Survival Differences in Admixed Patients With Breast Cancer.

OBJECTIVE: We aim to determine whether incremental changes in genetic ancestry percentages influence molecular and clinical outcome characteristics of breast cancer in an admixed population. BACKGROUND: Patients with breast cancer are predominantly characterized as "Black" or "White" based on self-identified race/ethnicity or arbitrary genetic ancestry cutoffs. This limits scientific discovery in populations that are admixed or of mixed race/ethnicity as they cannot be classified based on historical race/ethnicity boxes or genetic ancestry cutoffs. METHODS: We used The Cancer Genome Atlas cohort and focused on genetically admixed patients that had less than 90% European, African, Asian, or Native American ancestry. RESULTS: Genetically admixed patients with breast cancer exhibited improved 10-year overall survival relative to those with >90% European ancestry. Within the luminal A subtype, patients with lower African ancestry had longer 10-year overall survival compared to those with higher African ancestry. The correlation of genetic ancestry with gene expression and DNA methylation in the admixed cohort revealed novel ancestry-specific intrinsic PAM50 subtype patterns. In luminal A tumors, genetic ancestry was correlated with both the expression and methylation of signaling genes, while in basal-like tumors, genetic ancestry was correlated with stemness genes. In addition, we took a machine-learning approach to estimate genetic ancestry from gene expression or DNA methylation and were able to accurately calculate ancestry values from a reduced set of 10 genes or 50 methylation sites that were specific for each molecular subtype. CONCLUSIONS: Our results suggest that incremental changes in genetic ancestry percentages result in ancestry-specific molecular differences even between well-established PAM50 subtypes which may influence disparities in breast cancer survival outcomes. Accounting for incremental changes in ancestry will be important in future research, prognostication, and risk stratification, particularly in ancestrally diverse populations.

PRAME induces genomic instability in uveal melanoma.

PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME that can be targeted therapeutically in cancer.

Genome Wide Association Study of Neuropathic Ocular Pain.

Purpose: To conduct a genome-wide association study (GWAS) of individuals with neuropathic ocular pain (NOP) symptoms to identify genomic variants that may predispose to NOP development. Design: Prospective study of individuals with NOP. Participants: Three hundred twenty-nine patients recruited from the Miami Veterans Affairs eye clinic. Methods: The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-Eye) was completed to calculate a NPSI-Eye-Sub-Score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-Eye-Sub-Score with a significance threshold of P < 5 × 10-8. A gene-based analysis was performed using the multimarker analysis of genomic annotation software (in the functional mapping and annotation of GWAS online platform). The 13 865 778 single nucleotide polymorphisms (SNPs) from our GWAS analysis were mapped to 10 834 protein coding genes, and significant genes were run through gene set enrichment analysis. Main Outcome Measures: Identification of SNPs and protein products that may be associated with the development of NOP. Results: One hundred seventy-one SNPs reached a threshold of P < 10-5, of which 10 SNPs reached the suggestive level of significance of P < 5 × 10-7 and 1 SNP met our genome-wide significance threshold of P < 5 × 10-8. This lead SNP, rs140293404 (P = 1.23 × 10-8), is an intronic variant found within gene ENSG00000287251 coding for transcript ENST00000662732.1. Rs140293404 is in linkage disequilibrium with exon variant rs7926353 (r2 > 0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were matrix metalloproteinase-19 (MMP19) (P = 1.12 × 10-5), zinc finger RNA-binding motif and serine/arginine rich-1 (ZRSR1) (P = 1.48 × 10-4), CTC-487M23.8 (P = 1.79 × 10-4), receptor expression-enhancing protein-5 (REEP5) (P = 2.36 × 10-4), and signal recognition particle-19 (SRP19) (P = 2.56 × 10-4). From gene set enrichment analysis, the sensory perception (false discovery rate = 6.57 × 10-3) and olfactory signaling (false discovery rate = 1.63 × 10-2) pathways were enriched with the most significant genes. Conclusions: Our GWAS revealed genes with protein products that may impact sensory perception, lending biological plausibility to a role for SNPs identified by our GWAS in the development of NOP. A better understanding of the biological relevance of these genes and pathways in the pathophysiology associated with NOP may facilitate future novel mechanism-based treatments. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Recent greening may curb urban warming in Latin American cities of better economic conditions.

Rising temperatures have profound impacts on the well-being of urban residents. However, factors explaining the temporal variability of urban thermal environment, or urban warming, remain insufficiently understood, especially in the Global South. Addressing this gap, we studied the relationship between city-level economic conditions and urban warming, and how urban green space mediated this relationship, focusing on 359 major Latin American cities between 2001 and 2022. While effect sizes varied by economic and temperature measures used, we found that better economic conditions were associated with lower baseline greenness in 2011, which contributed to faster warming. There was modest evidence that this faster warming associated with lower baseline greenness and improved economic conditions was partially offset by cooling from recent greening (2001-2022) in cities of better economic conditions. This offset was more evident in arid cities. Together, these findings provide insights into the urban warming mechanism manifested through the effect of economic conditions on urban green space, for Latin American cities and other high-density cities transforming in a similar context.

Ambient nitrogen dioxide in 47 187 neighbourhoods across 326 cities in eight Latin American countries: population exposures and associations with urban features.

BACKGROUND: Health research on ambient nitrogen dioxide (NO2) is sparse in Latin America, despite the high prevalence of NO2-associated respiratory diseases in the region. This study describes within-city distributions of ambient NO2 concentrations at high spatial resolution and urban characteristics associated with neighbourhood ambient NO2 in 326 Latin American cities. METHODS: We aggregated estimates of annual surface NO2 at 1 km2 spatial resolution for 2019, population counts, and urban characteristics compiled by the SALURBAL project to the neighbourhood level (ie, census tracts). We described the percentage of the urban population living with ambient NO2 concentrations exceeding WHO air quality guidelines. We used multilevel models to describe associations of neighbourhood ambient NO2 concentrations with population and urban characteristics at the neighbourhood and city levels. FINDINGS: We examined 47 187 neighbourhoods in 326 cities from eight Latin American countries. Of the roughly 236 million urban residents observed, 85% lived in neighbourhoods with ambient annual NO2 above WHO guidelines. In adjusted models, higher neighbourhood-level educational attainment, closer proximity to the city centre, and lower neighbourhood-level greenness were associated with higher ambient NO2. At the city level, higher vehicle congestion, population size, and population density were associated with higher ambient NO2. INTERPRETATION: Almost nine out of every ten residents of Latin American cities live with ambient NO2 concentrations above WHO guidelines. Increasing neighbourhood greenness and reducing reliance on fossil fuel-powered vehicles warrant further attention as potential actionable urban environmental interventions to reduce population exposure to ambient NO2. FUNDING: Wellcome Trust, National Institutes of Health, Cotswold Foundation.

A scaling investigation of urban form features in Latin America cities.

This paper examines scaling behaviors of urban landscape and street design metrics with respect to city population in Latin America. We used data from the SALURBAL project, which has compiled and harmonized data on health, social, and built environment for 371 Latin American cities above 100,000 inhabitants. These metrics included total urbanized area, effective mesh size, area in km2 and number of streets. We obtained scaling relations by regressing log(metric) on log (city population). The results show an overall sub-linear scaling behavior of most variables, indicating a relatively lower value of each variable in larger cities. We also explored the potential influence of colonization on the current built environment, by analyzing cities colonized by Portuguese (Brazilian cities) or Spaniards (Other cities in Latin America) separately. We found that the scaling behaviors are similar for both sets of cities.

Greenness and excess deaths from heat in 323 Latin American cities: Do associations vary according to climate zone or green space configuration?

Green vegetation may protect against heat-related death by improving thermal comfort. Few studies have investigated associations of green vegetation with heat-related mortality in Latin America or whether associations are modified by the spatial configuration of green vegetation. We used data from 323 Latin American cities and meta-regression models to estimate associations between city-level greenness, quantified using population-weighted normalized difference vegetation index values and modeled as three-level categorical terms, and excess deaths from heat (heat excess death fractions [heat EDFs]). Models were adjusted for city-level fine particulate matter concentration (PM2.5), social environment, and country group. In addition to estimating overall associations, we derived estimates of association stratified by green space clustering by including an interaction term between a green space clustering measure (dichotomized at the median of the distribution) and the three-level greenness variable. We stratified analyses by climate zone (arid vs. temperate and tropical combined). Among the 79 arid climate zone cities, those with moderate and high greenness levels had modestly lower heat EDFs compared to cities with the lowest greenness, although protective associations were more substantial in cities with moderate versus high greenness levels and confidence intervals (CI) crossed the null (Beta: -0.41, 95% CI: -1.06, 0.25; Beta -0.23, 95% CI: -0.95, 0.49, respectively). In 244 non-arid climate zone cities, associations were approximately null. We did not observe evidence of effect modification by green space clustering. Our results suggest that greenness may offer modest protection against heat-related mortality in arid climate zone Latin American cities.

Effects of an urban cable car intervention on physical activity: the TrUST natural experiment in Bogotá, Colombia.

BACKGROUND: Cable cars are part of the transport system in several cities in Latin America, but no evaluations of their effects on physical activity are available. TransMiCable is the first cable car in Bogotá, Colombia, and the wider intervention includes renovated parks and playgrounds. We assessed the effects of TransMiCable and the wider intervention on physical activity. METHODS: The Urban Transformations and Health natural experiment was a prospective quasi-experimental study conducted from Feb 1, 2018, to Dec 18, 2018 (baseline, pre-intervention) and from July 2, 2019, to March 15, 2020 (post-intervention follow-up) in the TransMiCable intervention area (Ciudad Bolívar settlement) and a control area without TransMiCable (San Cristóbal settlement). A multistage strategy was used to sample households in each area, with one adult (aged ≥18 years) per household invited to participate. Eligible participants had lived in the intervention or control areas for at least 2 years and were not planning to move within the next 2 years. Physical activity was assessed among participants in the intervention and control areas before and after the inauguration of TransMiCable in Ciudad Bolívar with the International Physical Activity Questionnaire (long form) and with wearable accelerometers. Complete cases (those with baseline and follow-up data) were included in analyses. Respondents were classed as being physically active if they met 2020 WHO guidelines (≥150 min per week of moderate activity, ≥75 min per week of vigorous activity, or equivalent combinations); and accelerometery data were classified with the Freedson cut-points for adults. Data were also gathered in zonal parks (area ≥10 000 m2) and neighbourhood parks (area <10 000 m2) in the intervention and control areas by direct observation with the System for Observing Play and Recreation in Communities, to assess levels of physical activity before and after the TransMiCable intervention. Multilevel regression models were used to assess changes in physical activity associated with the TransMiCable intervention. FINDINGS: Physical activity questionnaires were completed by 2052 adult participants (1289 [62·8%] women and 763 [37·2%] men; mean age 43·5 years [SD 17·7]) before the inauguration of TransMiCable. After the inauguration, the follow-up (final) questionnaire sample comprised 825 adults in the intervention group and 854 in the control group, including 357 adults in the intervention group and 334 in the control group with valid accelerometery data. 334 (40·5%) of 825 participants in the intervention group reported levels of physical activity that met the 2020 WHO guidelines during walking for transport before the intervention, and 426 (51·6%) afterwards (change 11·1 percentage points [95% CI 6·4 to 15·9]). A similar change was observed in the control group (change 8·0 percentage points [3·4 to 12·5]; adjusted odds ratio [OR] for the time-by-group interaction, intervention vs control group: 1·1 [95% CI 0·8 to 1·5], p=0·38). Time spent doing moderate-to-vigorous physical activity, measured with accelerometers, did not change in the intervention group after the inauguration of TransMiCable (change -0·8 min per day [-4·6 to 3·0]) and did not change compared with the control group (adjusted ß for the time-by-group interaction: 1·4 min per day [95% CI -2·0 to 4·9], p=0·41). Moderate-to-vigorous physical activity was 52·1 min per day (SD 24·7) before and 59·4 min per day (35·2) after the inauguration of TransMiCable in new regular users who reported using TransMiCable during mandatory trips for work or education (n=32; change 7·3 min per day [-22·5 to 7·9]). After the intervention, an increase in the proportion of male individuals engaging in moderate or vigorous physical activity was observed in a renovated zonal park (adjusted OR for the time-by-group interaction, intervention vs control park: 2·7 [1·1 to 6·8], p=0·033). Female users of a renovated neighbourhood park were less likely to become engaged in moderate or vigorous physical activity than female users of the control area neighbourhood park (adjusted OR for the time-by-group interaction: 0·4 [0·1 to 0·6], p=0·019). INTERPRETATION: It is encouraging that walking for transport remained high in the TransMiCable intervention area when the use of private motorised transport had increased elsewhere in Bogotá. In low-income urban areas, where transport-related walking is a necessity, transport interventions should be focused on efforts to maintain participation in active travel while improving conditions under which it occurs. FUNDING: Wellcome Trust (as part of the Urban Health in Latin America project); Bogotá Urban Planning Department; Ministry of Science, Technology, and Innovation of Colombia; Universidad de Los Andes; Fundación Santa Fe de Bogotá; and Universidad del Norte. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

PRAME induces genomic instability in uveal melanoma.

PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME than can be targeted therapeutically in cancer.

Ambient nitrogen dioxide in 47,187 neighborhoods across 326 cities in eight Latin American countries: population exposures and associations with urban features.

Background: Health research on ambient nitrogen dioxide (NO2) is sparse in Latin America, despite the high prevalence of NO2-associated respiratory diseases in the region. This study describes within-city distributions of ambient NO2 concentrations at high spatial resolution and urban characteristics associated with neighborhood ambient NO2 in 326 Latin American cities. Methods: We aggregated estimates of annual surface NO2 at 1 km2 spatial resolution for 2019, population counts, and urban characteristics compiled by the SALURBAL project to the neighborhood level (i.e., census tracts). We described the percent of the urban population living with ambient NO2 levels exceeding WHO Air Quality Guidelines. We used multilevel models to describe associations of neighborhood ambient NO2 concentrations with population and urban characteristics at the neighborhood and city levels. Findings: We examined 47,187 neighborhoods in 326 cities from eight Latin American countries. Of the ≈236 million urban residents observed, 85% lived in neighborhoods with ambient annual NO2 above WHO guidelines. In adjusted models, higher neighborhood-level educational attainment, closer proximity to the city center, and lower neighborhood-level greenness were associated with higher ambient NO2. At the city level, higher vehicle congestion, population size, and population density were associated with higher ambient NO2. Interpretation: Almost nine out of every 10 residents of Latin American cities live with ambient NO2 concentrations above WHO guidelines. Increasing neighborhood greenness and reducing reliance on fossil fuel-powered vehicles warrant further attention as potential actionable urban environmental interventions to reduce population exposure to ambient NO2. Funding: Wellcome Trust, National Institutes of Health, Cotswold Foundation.

Impact of Tumor Necrosis Factor Receptor 1 (TNFR1) Polymorphism on Dry Eye Disease.

The goal of the study was to examine whether a genetic polymorphism in tumor necrosis factor receptor 1 (TNFR1) gene impacted the dry eye disease (DED) phenotype and response to anti-inflammatory therapy. The prospective study included 328 individuals with various dry eye (DE) symptoms and signs recruited from the Miami Veterans Hospital eye clinic between October 2013 and October 2017. The population underwent genetic profiling for a polymorphism within the TNFR1 gene (rs1800693 [TT, TC, CC]). The study examined the genotype distribution and relationships between the genotype, phenotype, and response to anti-inflammatory therapy. The mean age of the population was 61.7 ± 9.8 years. Here, 92% self-identified as male, 44% as White, and 21% as Hispanic; 13% (n = 42) of individuals had a CC genotype. DED symptoms and signs were similar across the three genotype groups. Thirty individuals (four with CC) were subsequently treated with an anti-inflammatory agent. There was a non-significant trend for individuals with CC genotype to have a partial or complete symptomatic response to treatment compared with the other two groups (100% for CC vs. 40% for TT and 36.4% for TC, p = 0.22). In conclusion, the presence of homozygosity of minor allele C (CC genotype) in a single nucleotide polymorphism (SNP) within TNFR1 was noted in a minority of individuals with various aspects of DED, but did not impact the DED phenotype. Our findings suggest that the current phenotyping strategies for DED are insufficient to identify underlying disease contributors, including potential genetic contributors.

Modification of temperature-related human mortality by area-level socioeconomic and demographic characteristics in Latin American cities.

BACKGROUND: In Latin America, where climate change and rapid urbanization converge, non-optimal ambient temperatures contribute to excess mortality. However, little is known about area-level characteristics that confer vulnerability to temperature-related mortality. OBJECTIVES: Explore city-level socioeconomic and demographic characteristics associated with temperature-related mortality in Latin American cities. METHODS: The dependent variables quantify city-specific associations between temperature and mortality: heat- and cold-related excess death fractions (EDF, or percentages of total deaths attributed to cold/hot temperatures), and the relative mortality risk (RR) associated with 1 °C difference in temperature in 325 cities during 2002-2015. Random effects meta-regressions were used to investigate whether EDFs and RRs associated with heat and cold varied by city-level characteristics, including population size, population density, built-up area, age-standardized mortality rate, poverty, living conditions, educational attainment, income inequality, and residential segregation by education level. RESULTS: We find limited effect modification of cold-related mortality by city-level demographic and socioeconomic characteristics and several unexpected associations for heat-related mortality. For example, cities in the highest compared to the lowest tertile of income inequality have all-age cold-related excess mortality that is, on average, 3.45 percentage points higher (95% CI: 0.33, 6.56). Higher poverty and higher segregation were also associated with higher cold EDF among those 65 and older. Large, densely populated cities, and cities with high levels of poverty and income inequality experience smaller heat EDFs compared to smaller and less densely populated cities, and cities with little poverty and income inequality. DISCUSSION: Evidence of effect modification of cold-related mortality in Latin American cities was limited, and unexpected patterns of modification of heat-related mortality were observed. Socioeconomic deprivation may impact cold-related mortality, particularly among the elderly. The findings of higher levels of poverty and income inequality associated with lower heat-related mortality deserve further investigation given the increasing importance of urban adaptation to climate change.

Actualización sobre el síndrome de Eagle y sus complicaciones neurocardiológicas: casos clínicos / An update on Eagle´s syndrome and its neuro-cardiological complications: clinical cases

El síndrome de Eagle o síndrome estilohioideo o sín-drome de la arteria carótida es un trastorno que se origina por la mineralización y elongación del pro-ceso estiloides. Factores traumáticos agudos y cró-nicos, así como otras teorías, han sido propuestos para explicar la etiología y patogenia de esta altera-ción. El conjunto de síntomas puede incluir: dolor fa-ríngeo, odinofagia, disfagia, cefalea, con irradiación a oreja y zona cervical. Si bien existen varias clasifi-caciones, de manera universal se acepta que existen principalmente dos formas de presentación de esta patología: el tipo I o clásico, generalmente asociado a un trauma faríngeo y acompañado de dolor en la zona faríngea y cervical, y el tipo II o carotídeo, que sue-le presentar molestia cervical, cefalea y alteración de la presión arterial, con riesgo de daño de la ac-tividad cardíaca. La identificación de este síndrome suele ser confusa dada la similitud de los síntomas con otras afecciones. El diagnóstico debe realizarse en base a los síntomas y a los estudios por imágenes específicos. El tratamiento puede ser conservador y actuar simplemente sobre los síntomas, o bien, qui-rúrgico. El objetivo del presente trabajo es realizar una revisión actualizada de la literatura sobre el sín-drome de Eagle y presentar tres casos clínicos con distintas manifestaciones (AU)

Eagle's syndrome or styloid syndrome or stylo-carotid artery syndrome is a disease caused by mineralization and elongation of the styloid process. Acute and chronic traumatic factors, along with other hypothesis, have been proposed to explain the aetiology and pathogenesis of this condition. Symptoms can include: pharynx pain, odynophagia, dysphagia, headache, with radiating pain to the ear and neck. Despite there are several classifications, it is universally accepted that this pathology can present in two forms: the type I or classic, generally associated to tonsillar trauma and characterized by pharyngeal and neck pain, and the type II or carotid artery type, which frequently presents with neck pain, headache, blood pressure variation, with risk of damage to cardiac function. Identifying of Eagle's syndrome is often confusing because some symptoms are shared with other pathologies. Diagnosis must be made on the basis of symptoms and imaging studies. Treatment can be conservative, acting only on symptoms, or surgical. The aim of this paper is to provide an updated review of the literature on Eagle syndrome and to present three clinical cases with different manifestations (AU)