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To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression.Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown.Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease.Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC.In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

Study designs involving randomization can be difficult to communicate to participants, especially those with low literacy. The literature on strategies to explain research concepts is limited, especially for non-English speakers. We measured the effectiveness of a culturally and contextually situated multimedia approach to recruit a cohort of 60 female Mexican immigrants (FMI) to a randomized control trial (RCT) to reduce social isolation and depression. This strategy was designed to explain the concept of randomization, explain what participating in the research study entailed, and ensure informed consent. Potential participants viewed a presentation explaining the study and a video including animation with voice-over explaining the concept of randomization. We administered a pre/post survey. Respondents ( N = 59) reported an increase in their understanding of randomization, intention to enroll, and attitude towards participating in research. We conclude that a culturally and contextually situated multimedia approach is an effective model when recruiting underrepresented populations with low literacy for RCTs.

Dry eye disease (DED) is a diagnosis given to individuals with a heterogeneous combination of symptoms and/or signs, including spontaneous and evoked ocular pain. Our current study evaluated whether and which ocular pain assessments could serve as screening tools for central sensitization in individuals with DED. A cohort of individuals with DED symptoms (n = 235) were evaluated for ocular pain, DED signs (tear production, evaporation), evoked sensitivity to mechanical stimulation at the cornea, and evidence of central sensitization. Central sensitization was defined for this study as the presence of pain 30 seconds after termination of a thermal noxious temporal summation protocol (ie, aftersensations) presented at a site remote from the eye (ventral forearm). We found that combining ratings of average intensity of ocular pain, ratings of average intensity of pain due to light, response to topical anesthetic eye drops, and corneal mechanical pain thresholds produced the best predictive model for central sensitization (area under the curve of .73). When examining ratings of intensity of ocular pain due to light alone (0-10 numerical rating), a cutoff score of 2 maximized sensitivity (85%) and specificity (48%) for the presence of painful aftersensations at the forearm. Self-reported rating of pain sensitivity to light may serve as a quick screening tool indicating the involvement of central nociceptive system dysfunction in individuals with DED. PERSPECTIVE: This study reveals that clinically-relevant variables, including a simple 0 to 10 rating of ocular pain due to light, can be used to predict the contribution of central sensitization mechanisms in a subgroup of individuals with DED symptoms. These findings can potentially improve patient stratification and management for this complex and painful disease.

Background Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients with chronic kidney disease (CKD). Therapies that improve morbidity and mortality in HFpEF are lacking. Cell-based therapies promote cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that cell-based therapy ameliorates CKD-induced HFpEF. Methods and Results Yorkshire pigs (n = 26) underwent 5/6 embolization-mediated nephrectomy. CKD was confirmed by increased creatinine and decreased glomerular filtration rate (GFR). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. HFpEF was evident at 4 weeks by increased LV mass, relative wall thickening, end-diastolic pressure, and end-diastolic pressure-volume relationship, with no change in ejection fraction (EF). Four weeks post-embolization, allogeneic (allo) bone marrow-derived mesenchymal stem cells (MSC; 1 × 107 cells), allo-kidney-derived stem cells (KSC; 1 × 107 cells), allo-cell combination therapy (ACCT; MSC + KSC; 1:1 ratio; total = 1 × 107 cells), or placebo (Plasma-Lyte) was delivered via intra-renal artery. Eight weeks post-treatment, there was a significant increase in MAP in the placebo group (21.89 ± 6.05 mmHg) compared to the ACCT group. GFR significantly improved in the ACCT group. EF, relative wall thickness, and LV mass did not differ between groups at 12 weeks. EDPVR improved in the ACCT group, indicating decreased ventricular stiffness. Conclusions Intra-renal artery allogeneic cell therapy was safe in a CKD swine model manifesting the characteristics of HFpEF. The beneficial effect on renal function and ventricular compliance in the ACCT group supports further research of cell therapy for cardiorenal syndrome.

Purpose This study sought to evaluate whether associations between adolescent combustible cigarette smoking and e-cigarette progression were explained by beliefs that e-cigarettes substitute for cigarettes in nonsmoking situations. Methods Adolescents (N = 1,799) from public high schools outside of Philadelphia, PA, completed in-classroom surveys at wave 1 (fall 2016, beginning of ninth grade) and at 6-month intervals for the following 36 months (fall 2019, beginning of 12th grade). Results A parallel process latent growth curve model revealed that the pathway from baseline smoking to e-cigarette use trend through baseline e-cigarette substitution beliefs was significant (B = .02, z = 2.16, p = .03), indicating that the positive effect of greater baseline cigarette smoking on the rate of e-cigarette progression was channeled through e-cigarette substitution beliefs. The indirect effect from baseline smoking to e-cigarette use trend via e-cigarette substitution beliefs trend was also significant, albeit negative (B = -.05, z = -2.61, p = .009). The negative indirect effect suggested that the strong positive effect of baseline cigarette smoking on baseline substitution beliefs was followed by a slowing of the overall rate of change from baseline. Given that the total effect from baseline smoking to e-cigarette trend was not significant (p = .91), the results suggested complete mediation. Conclusions Among adolescents with greater use of combustible cigarettes, beliefs regarding the substitutability of e-cigarettes in nonsmoking situations appear to foster progression in e-cigarette use. Addressing these beliefs in the school setting and through media campaign messaging early in adolescence may help to prevent the use of e-cigarettes and combustible cigarettes.

Latin America is the world’s most urbanized region and its heterogeneous urban development may impact chronic diseases. Here, we evaluated the association of built environment characteristics at the sub-city —intersection density, greenness, and population density— and city-level —fragmentation and isolation— with body mass index (BMI), obesity, and type 2 diabetes (T2D). Data from 93,280 (BMI and obesity) and 122,211 individuals (T2D) was analysed across 10 countries. Living in areas with higher intersection density was positively associated with BMI and obesity, whereas living in more fragmented and greener areas were negatively associated. T2D was positively associated with intersection density, but negatively associated with greenness and population density. The rapid urban expansion experienced by Latin America provides unique insights and vastly expand opportunities for population-wide urban interventions aimed at reducing obesity and T2D burden.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype–phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4 , MUC21 and MUC22 , TOX2 , ANXA6 , and ABCA1 ) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

Summary Background Little is known about the effect of changes in mobility at the subcity level on subsequent COVID-19 incidence, which is particularly relevant in Latin America, where substantial barriers prevent COVID-19 vaccine access and non-pharmaceutical interventions are essential to mitigation efforts. We aimed to examine the longitudinal associations between population mobility and COVID-19 incidence at the subcity level across a large number of Latin American cities. Methods In this longitudinal ecological study, we compiled aggregated mobile phone location data, daily confirmed COVID-19 cases, and features of urban and social environments to analyse population mobility and COVID-19 incidence at the subcity level among cities with more than 100 000 inhabitants in Argentina, Brazil, Colombia, Guatemala, and Mexico, from March 2 to Aug 29, 2020. Spatially aggregated mobile phone data were provided by the UN Development Programme in Latin America and the Caribbean and Grandata; confirmed COVID-19 cases were from national government reports and population and socioeconomic factors were from the latest national census in each country. We used mixed-effects negative binomial regression for a time-series analysis, to examine longitudinal associations between weekly mobility changes from baseline (prepandemic week of March 2–9, 2020) and subsequent COVID-19 incidence (lagged by 1–6 weeks) at the subcity level, adjusting for urban environmental and socioeconomic factors (time-invariant educational attainment, residential overcrowding, population density [all at the subcity level], and country). Findings We included 1031 subcity areas, representing 314 Latin American cities, in Argentina (107 subcity areas), Brazil (416), Colombia (82), Guatemala (20), and Mexico (406). In the main adjusted model, we observed an incidence rate ratio (IRR) of 2·35 (95% CI 2·12–2·60) for COVID-19 incidence per log unit increase in the mobility ratio (vs baseline) during the previous week. Thus, 10% lower weekly mobility was associated with 8·6% (95% CI 7·6–9·6) lower incidence of COVID-19 in the following week. This association gradually weakened as the lag between mobility and COVID-19 incidence increased and was not different from null at a 6-week lag. Interpretation Reduced population movement within a subcity area is associated with a subsequent decrease in COVID-19 incidence among residents of that subcity area. Policies that reduce population mobility at the subcity level might be an effective COVID-19 mitigation strategy, although they should be combined with strategies that mitigate any adverse social and economic consequences of reduced mobility for the most vulnerable groups. Funding Wellcome Trust. Translation For the Spanish translation of the abstract see Supplementary Materials section.

Objective This study aimed to develop and internally validate risk prediction models for predicting groin wound surgical site infections (SSIs) following arterial intervention and to evaluate the utility of existing risk prediction models for this outcome. Methods Data from the Groin wound Infection after Vascular Exposure (GIVE) multicentre cohort study were used. The GIVE study prospectively enrolled 1 039 consecutive patients undergoing an arterial procedure through 1 339 groin incisions. An overall SSI rate of 8.6% per groin incision, and a deep/organ space SSI rate of 3.8%, were reported. Eight independent predictors of all SSIs, and four independent predictors of deep/organ space SSIs were included in the development and internal validation of two risk prediction models. A systematic search of the literature was conducted to identify relevant risk prediction models for their evaluation. Results The “GIVE SSI risk prediction model” (“GIVE SSI model”) and the “GIVE deep/organ space SSI risk prediction model” (“deep SSI model”) had adequate discrimination (C statistic 0.735 and 0.720, respectively). Three other groin incision SSI risk prediction models were identified; both GIVE risk prediction models significantly outperformed these other risk models in this cohort (C statistic 0.618 – 0.629; p Conclusion Two models were created and internally validated that performed acceptably in predicting “all” and “deep” groin SSIs, outperforming current existing risk prediction models in this cohort. Future studies should aim to externally validate the GIVE models.

PURPOSE: We sought to evaluate if internalizing symptoms (i.e., anxiety, depression) and/or externalizing symptoms (i.e., impulsivity, sensation-seeking, and substance use) were risk factors for the onset of 30-day e-cigarette use and escalation in the number of days used across the following 30 months among adolescents. METHODS: Adolescents (N = 1808) from public high schools outside of Philadelphia, PA completed in-classroom surveys at wave 1 (fall 2016, beginning of 9(th) grade) and at 6-month intervals for the following 30 months (spring 2019, end of 11(th) grade). RESULTS: A two-part Latent Growth Curve Model of e-cigarette use revealed significant positive associations between externalizing factors, past 30-day e-cigarette use, and the number of days of e-cigarette use only at wave 1 (p values < .05). Cigarette smoking was associated with a slowing in the rate of onset of 30-day e-cigarette use across the 30-month follow-up (β = −0.24, z = −2.41, p = 0.02). Depression was associated with an increased rate of escalation in the number of days of e-cigarette use across the following 30-months (β = 0.01, z = 2.52, p = 0.01), while anxiety was associated with a decrease (β = −0.72, z = −2.36, p = 0.02). CONCLUSIONS: The findings highlight two groups of adolescents at risk for e-cigarette use: adolescents whose e-cigarette use reflects a higher-risk profile with early e-cigarette onset, and adolescents who have a lower-risk profile, at least initially, with later e-cigarette use onset. The timing and content of prevention efforts should be tailored to each group.

Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. OBJECTIVES The study sought to assess COVID-19`s impact on global cardiovascular diagnostic procedural volumes and safety practices. METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. RESULTS Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoradc echocardiography decreased by 59%, transesophageat echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). hi multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and teteheatth. CONCLUSIONS COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Background Transport walking has drawn growing interest due to its potential to increase levels of physical activities and reduce reliance on vehicles. While existing studies have compared built environment-health associations between Euclidean buffers and network buffers, no studies have systematically quantified the extent of bias in health effect estimates when exposures are measured in different buffers. Further, prior studies have done the comparisons focusing on only one or two geographic regions, limiting generalizability and restricting ability to test whether direction or magnitude of bias are different by context. This study aimed to quantify the degree of bias in associations between built environment exposures and transport walking when exposures were operationalized using Euclidean buffers rather than network buffers in diverse contexts. Methods We performed a simulations study to systematically evaluate the degree of bias in associations between built environment exposures in Euclidean buffers and network buffers and transport walking, assuming network buffers more accurately captured true exposures. Additionally, we used empirical data from a multi-ethnic, multi-site cohort to compare associations between built environment amenities and walking for transport where built environment exposures were derived using Euclidean buffers versus network buffers. Results Simulation results found that the bias induced by using Euclidean buffer models was consistently negative across the six study sites (ranging from -80% to -20%), suggesting built environment exposures measured using Euclidean buffers underestimate health effects on transport walking. Percent bias was uniformly smaller for the larger 5 km scale than the 1 km and 0.25 km spatial scales, independent of site or built environment categories. Empirical findings aligned with the simulation results: built environment-health associations were stronger for built environment exposures operationalized using network buffers than using Euclidean buffers. Conclusion This study is the first to quantify the extent of bias in the magnitude of the associations between built environment exposures and transport walking when the former are measured in Euclidean buffers vs. network buffers, informing future research to carefully conceptualize appropriate distance-based buffer metrics in order to better approximate real geographic contexts. It also helps contextualize existing research in the field that used Euclidean buffers when that were the only option. Further, this study provides an example of the uncertain geographic context problem.

IntroductionWe evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle.MethodsParticipants from population-based samples ≥60 years of age (n=623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans.ResultsTsimane exhibited five cases of dementia (among n=435; crude prevalence=1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n=169; crude prevalence=0.6%, 95% CI: 0.0, 3.2), all age≥80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia.DiscussionThe prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

The purpose of this paper is to verify whether the concentrations of caffeine in saliva are comparable to serum concentrations in preterm infants who are treated with caffeine for apnea of prematurity. This is a prospective observational study. Eligible participants were newborn infants 37 weeks of gestational age treated with oral or intravenous caffeine for apnea of prematurity. Two paired samples of saliva and blood were collected per patient. Tube solid-phase microextraction coupled online to capillary liquid chromatography with diode array detection was used for analysis. A total of 47 infants with a median gestational age of 28 [26-30] weeks and a mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29-33] weeks. Serum caffeine median levels of 19.30 μg/mL [1.9-53.90] and salivary caffeine median levels of 16.36 μg/mL [2.20-56.90] were obtained. There was a strong positive Pearson's correlation between the two variables r = 0.83 (p 0.001).The measurement of salivary caffeine concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnea of prematurity. Measurement of salivary concentration minimizes blood draws, improves blood conservation, and subsequently minimizes painful procedures in premature infants.• Salivary sampling may be useful when is applied to extremely low birth weight infant, in whom blood sampling must be severely restricted.• The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity. • Salivary sampling may be a valid non-invasive alternative that could be used to individualize and optimize caffeine dose.

Background Recent studies highlight the equigenic potential of greenspaces by showing narrower socioeconomic health inequalities in greener areas. However, results to date have been inconsistent and derived from high-income countries. We examined whether urban greenness modifies the associations between area-level education, as a proxy for socioeconomic status, and life expectancy and cause-specific mortality in Latin American cities. Methods We included 28 large cities, >137 million inhabitants, in nine Latin American countries, comprising 671 sub-city units, for 2012–2016. Socioeconomic status was assessed through a composite index of sub-city level education, and greenness was calculated using the normalized difference vegetation index. We fitted multilevel models with sub-city units nested in cities, with life expectancy or log(mortality) as the outcome. Findings We observed a social gradient, with higher levels of education associated with higher life expectancy and lower cause-specific mortality. There was weak evidence supporting the equigenesis hypothesis as greenness differentially modified the association between education and mortality outcomes. We observed an equigenic effect, with doubling magnitudes in the violence-related mortality reduction by education in areas with low greenness compared to medium-high greenness areas among men (16% [95% CI 12%–20%] vs 8% [95% CI 4%–11%] per 1 SD increase in area-level education). However, in contradiction to the equigenesis hypothesis, the magnitude in cardiovascular diseases (CVD) mortality reduction by education was stronger in areas with medium-high greenness compared to areas with low greenness (6% [95% CI 4%–7%] vs 1% [95% CI -1%–3%] and 5% [95% CI 3%–7%] vs 1% [95% CI -1%–3%] per 1 SD increase in area-level education, in women and men, respectively). Similarly, each 1-SD increase in greenness widened the educational inequality in life expectancy by 0.15 years and 0.20 years, in women and men, respectively. The equigenic effect was not observed in violence-related mortality among women and in mortality due to communicable diseases, maternal, neonatal and nutritional conditions (CMNN). Interpretation Our results confirm socioeconomic health inequalities in Latin American cities and show that the equigenic properties of greenspace vary by health outcome. Although mixed, our findings suggest that future greening policies should account for local social and economic conditions to ensure that greenspaces provide health benefits for all, and do not further exacerbate existing health inequalities in the region. Funding Wellcome Trust (Grant, 205177/Z/16/Z)., Highlights • This study is the first to examine the equigenesis hypothesis of greenspace in Latin America. • Higher education was associated with higher life-expectancy and lower cause-specific mortality. • Education disparities in violence-related mortality were narrower in greener areas. • Greener areas had wider education disparities in life-expectancy and CVD mortality.

Background: Living in deprived areas is associated with poorer outcomes after certain vascular procedures and surgical site infection in other specialties. Our primary objective was to determine whether living in more income-deprived areas was associated with groin wound surgical site infection after arterial intervention. Secondary objectives were to determine whether living in more income-deprived areas was associated with mortality and clinical consequences of surgical site infection. Methods: Postal code data for patients from the United Kingdom who were included in the Groin Wound Infection after Vascular Exposure (GIVE) multicenter cohort study was used to determine income deprivation, based on index of multiple deprivation (IMD) data. Patients were divided into three IMD groups for descriptive analysis. Income deprivation score was integrated into the final multivariable model for predicting surgical site infection. Results: Only patients from England had sufficient postal code data, analysis included 772 groin incisions (624 patients from 22 centers). Surgical site infection occurred in 9.7% incisions (10.3% of patients). Surgical site infection was equivalent between income deprivation tertiles (tertile 1 = 9.5%; tertile 2 = 10.3%; tertile 3 = 8.6%; p = 0.828) as were the clinical consequences of surgical site infection and mortality. Income deprivation was not associated with surgical site infection in multivariable regression analysis (odds ratio [OR], 0.574; 95% confidence interval [CI], 0.038-8.747; p = 0.689). Median age at time of procedure was lower for patients living in more income-deprived areas (tertile 1 = 68 years; tertile 2 = 72 years; tertile 3 = 74 years; p

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population., eLife digest Genes contain the instructions needed for a cell to make molecules called proteins, which perform various roles in the body. Different variants of a gene can affect how the protein works, and in some cases, can increase a person’s risk to develop certain diseases. For example, people who carry a version of the apolipoprotein E gene called APOE4 have a greater risk of developing Alzheimer’s disease or heart disease. Individuals with two copies of this genetic variant have a 45% higher risk of heart disease and 12 times higher risk of Alzheimer’s disease. Studies in industrialized countries suggest this increased risk may be the result of higher cholesterol and inflammation in people with APOE4. But if APOE4 is harmful, why does it continue to be so common worldwide? One potential explanation is that APOE4, which has been around since before modern humans, may be beneficial in some contexts. Cholesterol is essential for many vital tasks in the body. In physically demanding environments where parasitic infections are common – conditions similar to those experienced by early humans – APOE4 might be beneficial. Under those circumstances, having more cholesterol might help fuel metabolic activities, fight infections, or reduce inflammation caused by infections. Garcia et al. investigated the link between the APOE4 genetic variant, cholesterol and inflammation in 1,266 Indigenous Tsimane people from 80 villages in Bolivia. Tsimane people live an active lifestyle foraging and farming for food. Parasite infections are a common problem in their communities, but obesity rates are very low. Garcia et al. found that Tsimane people with at least one copy of the APOE4 have lower levels of inflammation and higher levels of cholesterol than those who have two copies of the APOE3 version of the gene. Very lean people with APOE4 had especially high levels of the so called “bad” low density lipoprotein (LDL) cholesterol compared to people with APOE3 only. However, in this situation, storing a little extra cholesterol may not be so bad. The findings contradict other studies that have linked obesity to higher LDL levels and APOE4 to higher levels of inflammation. For the majority of human history, humans lived in more physically strenuous and calorically restrictive environments, with less access to clean water. Garcia et al. suggest that the harmful effects of APOE4 seen in studies in more industrialized societies – where people tend to be more sedentary and have less exposure to pathogens – may reflect a mismatch between a person’s environment and their genes. More studies that capture the diversity of environmental conditions under which people live will help clarify the role of APOE4 health and disease.

Active transportation (AT) is widely viewed as an important target for increasing participation in aerobic physical activity and improving health, while simultaneously addressing pollution and climate change through reductions in motor vehicular emissions. In recent years, progress in increasing AT has stalled in some countries and, furthermore, the coronavirus (COVID-19) pandemic has created new AT opportunities while also exposing the barriers and health inequities related to AT for some populations. This paper describes the results of the December 2019 Conference on Health and Active Transportation (CHAT) which brought together leaders from the transportation and health disciplines. Attendees charted a course for the future around three themes: Reflecting on Innovative Practices, Building Strategic Institutional Relationships, and Identifying Research Needs and Opportunities. This paper focuses on conclusions of the Research Needs and Opportunities theme. We present a conceptual model derived from the conference sessions that considers how economic and systems analysis, evaluation of emerging technologies and policies, efforts to address inclusivity, disparities and equity along with renewed attention to messaging and communication could contribute to overcoming barriers to development and use of AT infrastructure. Specific research gaps concerning these themes are presented. We further discuss the relevance of these themes considering the pandemic. Renewed efforts at research, dissemination and implementation are needed to achieve the potential health and environmental benefits of AT and to preserve positive changes associated with the pandemic while mitigating negative ones.

BACKGROUND: Depression symptoms are associated with the initiation of cigarette smoking and progression to regular use. Whether similar relationships exist between depression symptoms and adolescent e-cigarette progression has not been firmly established. METHODS: This prospective longitudinal survey study measured the relationship between depression symptoms and e-cigarette use among 1822 adolescents from four public high schools outside of Philadelphia, PA. Adolescents completed in-classroom surveys at wave 1 (fall 2016, 9(th) grade) and 6-month intervals for the following 36 months (fall 2019, 12(th) grade). E-cigarette use, depression symptoms, and potential covariates were measured at each wave. A latent growth curve model was used to assess the longitudinal relationship between e-cigarette use and depression symptoms. RESULTS: Baseline depressive symptoms had a significant effect on e-cigarette use trend (b=0.01, z=4.29, p < 0.0001) while holding other variables constant. A standard deviation increase in depressive symptoms at baseline was associated with a 0.25 standard deviation increase in the rate of e-cigarette progression across the following 36 months. By contrast, the path from baseline e-cigarette use to depressive symptoms trend was not significant (p = 0.74). CONCLUSIONS: The present study provides new evidence for the effects of depression symptoms on adolescent e-cigarette progression. Greater depressive symptoms at age 14 years old were associated with a faster rate of e-cigarette escalation. However, e-cigarette use was not related to the development of depression symptoms over time. It will be important to examine whether adolescents with elevated depression symptoms respond similarly to e-cigarette prevention campaigns as adolescents in general.

Virtual audits using Google Street View are an increasingly popular method of assessing neighborhood environments for health and urban planning research. However, the validity of these studies may be threatened by issues of image availability, image age, and variance of image age, particularly in the Global South. This study identifies patterns of Street View image availability, image age, and image age variance across cities in Latin America and assesses relationships between these measures and measures of resident socioeconomic conditions. Image availability was assessed at 530,308 near-road points within the boundaries of 371 Latin American cities described by the SALURBAL (Salud Urbana en America Latina) project. At the subcity level, mixed-effect linear and logistic models were used to assess relationships between measures of socioeconomic conditions and image availability, average image age, and the standard deviation of image age. Street View imagery was available at 239,394 points (45.1%) of the total sampled, and rates of image availability varied widely between cities and countries. Subcity units with higher scores on measures of socioeconomic conditions had higher rates of image availability (OR = 1.11 per point increase of combined index, p < 0.001) and the imagery was newer on average (− 1.15 months per point increase of combined index, p < 0.001), but image capture date within these areas varied more (0.59-month increase in standard deviation of image age per point increase of combined index, p < 0.001). All three assessed threats to the validity of Street View virtual audit studies spatially covary with measures of socioeconomic conditions in Latin American cities. Researchers should be attentive to these issues when using Street View imagery. Electronic supplementary material The online version of this article (10.1007/s11524-019-00408-7) contains supplementary material, which is available to authorized users.

Uveal melanoma (UM) is a highly metastatic cancer that, in contrast to cutaneous melanoma, is largely unresponsive to checkpoint immunotherapy. Here, we interrogate the tumor microenvironment at single-cell resolution using scRNA-seq of 59,915 tumor and non-neoplastic cells from 8 primary and 3 metastatic samples. Tumor cells reveal novel subclonal genomic complexity and transcriptional states. Tumor-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including CD8+ T cells predominantly expressing the checkpoint marker LAG3, rather than PD1 or CTLA4. V(D)J analysis shows clonally expanded T cells, indicating that they are capable of mounting an immune response. An indolent liver metastasis from a class 1B UM is infiltrated with clonally expanded plasma cells, indicative of antibody-mediated immunity. This complex ecosystem of tumor and immune cells provides new insights into UM biology, and LAG3 is identified as a potential candidate for immune checkpoint blockade in patients with high risk UM., Uveal melanoma is highly metastatic and unresponsive to checkpoint immunotherapy. Here, the authors present single-cell transcriptomics of 59,915 cells in 8 primary and 3 metastatic samples, highlighting the diversity of the tumour microenvironment.

We explored associations between residential preferences and sociodemographic characteristics, the concordance between current neighborhood characteristics and residential preferences, and heterogeneity in concordance by income and race/ethnicity. Data came from a cross-sectional phone and mail survey of 3668 residents of New York City, Baltimore, Chicago, Los Angeles, St. Paul, and Winston Salem in 2011-12. Scales characterized residential preferences and neighborhood characteristics. Stronger preferences were associated with being older, female, non-White/non-Hispanic, and lower education. There was significant positive but weak concordance between current neighborhood characteristics and residential preferences (after controlling sociodemographic characteristics). Concordance was stronger for persons with higher income and for Whites, suggesting that residential self-selection effects are strongest for populations that are more advantaged.

There is limited empirical evidence on how travel time affects dietary patterns, and even less in Latin American cities (LACs). Using data from 181 LACs, we investigated whether longer travel times at the city level are associated with lower consumption of vegetables and higher consumption of sugar-sweetened beverages and if this association differs by city size. Travel time was measured as the average city-level travel time during peak hours and city-level travel delay time was measured as the average increase in travel time due to congestion on the street network during peak hours. Vegetables and sugar-sweetened beverages consumption were classified according to the frequency of consumption in days/week (5–7: “frequent”, 2–4: “medium”, and ≤1: “rare”). We estimate multilevel ordinal logistic regression modeling for pooled samples and stratified by city size. Higher travel time (Odds Ratio (OR) = 0.65; 95% Confidence Interval (CI) 0.49–0.87) and delay time (OR = 0.57; CI 0.34–0.97) were associated with lower odds of frequent vegetable consumption. For a rare SSB consumption, we observed an inverse association with the delay time (OR = 0.65; CI 0.44–0.97). Analysis stratified by city size show that these associations were significant only in larger cities. Our results suggest that travel time and travel delay can be potential urban determinants of food consumption.

Retinal degenerative diseases such as retinitis pigmentosa cause a progressive loss of photoreceptors that eventually prevents the affected person from perceiving visual sensations. The absence of a visual input produces a neural rewiring cascade that propagates along the visual system. This remodeling occurs first within the retina. Then, subsequent neuroplastic changes take place at higher visual centers in the brain, produced by either the abnormal neural encoding of the visual inputs delivered by the diseased retina or as the result of an adaptation to visual deprivation. While retinal implants can activate the surviving retinal neurons by delivering electric current, the unselective activation patterns of the different neural populations that exist in the retinal layers differ substantially from those in physiologic vision. Therefore, artificially induced neural patterns are being delivered to a brain that has already undergone important neural reconnections. Whether or not the modulation of this neural rewiring can improve the performance for retinal prostheses remains a critical question whose answer may be the enabler of improved functional artificial vision and more personalized neurorehabilitation strategies.

OBJECTIVES In this study, we sought to identify which adolescents progress to regular electronic cigarette (e-cigarette) use (without cigarette smoking), which adolescents become dual users of both types of cigarettes, and how dual use develops across time. METHODS Adolescents (N = 1808) from public high schools outside Philadelphia, Pennsylvania, completed in-classroom surveys at wave 1 (fall 2016, beginning of ninth grade) and at 6-month intervals for the following 36 months (fall 2019, beginning of 12th grade). RESULTS A sequential processes growth mixture model identified 4 conjoint latent classes: later, rapid e-cigarette uptake (class 1: n = 230); no use of e-cigarettes or combustible cigarettes (class 2: n = 1141); earlier, steady e-cigarette uptake (class 3: n = 265); and dual use of e-cigarettes and combustible cigarettes (class 4: n = 204). Using a rich set of potential risk factors, multinomial logistic regression assessed the likelihood of belonging to each conjoint class compared with the comparison class (dual use). Adolescents in the dual use class were characterized by a greater number and severity of e-cigarette and combustible cigarette risk factors. Adolescents in the 2 e-cigarettes–only classes were characterized by either e-cigarette–specific risk factors (earlier onset) or no risk factors (later onset). The no use class had an absence of risk factors for e-cigarette and cigarette use. CONCLUSIONS This study provides new prospective evidence for distinct patterns and profiles of adolescents who progress to current e-cigarette use, including adolescents who were initially cigarette smokers. The findings have implications for prevention intervention timing, tobacco product focus, content, and the adolescent subgroups to target.

Few studies have examined associations between neighborhood built environments (BE) and longitudinally measured cognition. We examined whether four BE characteristics were associated with six-year change in global cognition and processing speed. We obtained data on 1816 participants without dementia from the Multi-Ethnic Study of Atherosclerosis. BE measures included social destination density, walking destination density, proportion of land dedicated to retail, and network ratio (street connectivity). Global cognition was measured with the Cognitive Abilities Screening Instrument (CASI) and processing speed with the Digit Symbol Coding test (DSC). Multivariable random intercept logistic models tested associations between neighborhood BE at 2010–2012 and maintained/improved cognition (versus decline) from 2010–2018, and mediation by minutes of physical activity (PA)/week. The sample was an average of 67 years old (standard deviation = 8.2) (first cognitive measurement) and racially/ethnically diverse (29% African American, 11% Chinese, 17% Hispanic, 44% White). Compared to individuals with no walking destinations in the 1-mile surrounding their residence, those with 716 walking destinations (maximum observed) were 1.24 times more likely to have maintain/improved DSC score (Odds ratio: 1.24, 95% confidence interval: 1.03–1.45). No other associations were observed between BE and cognition, and PA minutes/week did not mediate the association between walking destination density and DSC change. This study provides limited evidence for an association between greater neighborhood walking destinations and maintained/improved processing speed in older age and no evidence for associations between the other BE characteristics and cognition. Future studies with finer grained BE and cognitive measures and longer-term follow up may be required.

Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p < 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures.

National audience; Background: Atrial fibrillation is the most common arrhythmia in post-industrialized populations. Older age, hypertension, obesity, chronic inflammation, and diabetes are significant atrial fibrillation risk factors, suggesting that modern urban environments may promote atrial fibrillation.Objective: Here we assess atrial fibrillation prevalence and incidence among tropical horticulturalists of the Bolivian Amazon with high levels of physical activity, a lean diet, and minimal coronary atherosclerosis, but also high infectious disease burden and associated inflammation.Methods: Between 2005–2019, 1314 Tsimane aged 40–94 years (52% female) and 534 Moseten Amerindians aged 40–89 years (50% female) underwent resting 12-lead electrocardiograms to assess atrial fibrillation prevalence. For atrial fibrillation incidence assessment, 1059 (81% of original sample) Tsimane and 310 Moseten (58%) underwent additional ECGs (mean time to follow up 7.0, 1.8 years, respectively).Findings:Only one (male) of 1314 Tsimane (0.076%) and one (male) of 534 Moseten (0.187%) demonstrated atrial fibrillation at baseline. There was one new (female) Tsimane case in 7395 risk years for the 1059 participants with >1 ECG (incidence rate = 0.14 per 1,000 risk years). No new cases were detected among Moseten, based on 542 risk years.Conclusion: Tsimane and Moseten show the lowest levels of atrial fibrillation ever reported, 1/20 to ~1/6 of rates in high-income countries. These findings provide additional evidence that a subsistence lifestyle with high levels of physical activity, and a diet low in processed carbohydrates and fat is cardioprotective, despite frequent infection-induced inflammation. Findings suggest that atrial fibrillation is a modifiable lifestyle disease rather than an inevitable feature of cardiovascular aging.

The built environment of cities is complex and influences social and environmental determinants of health. In this study we, 1) identified city profiles based on the built landscape and street design characteristics of cities in Latin America and 2) evaluated the associations of city profiles with social determinants of health and air pollution. Landscape and street design profiles of 370 cities were identified using finite mixture modeling. For landscape, we measured fragmentation, isolation, and shape. For street design, we measured street connectivity, street length, and directness. We fitted a two-level linear mixed model to assess the association of social and environmental determinants of health with the profiles. We identified four profiles for landscape and four for the street design domain. The most common landscape profile was the “proximate stones” characterized by moderate fragmentation, isolation and patch size, and irregular shape. The most common street design profile was the “semi-hyperbolic grid” characterized by moderate connectivity, street length, and directness. The “semi-hyperbolic grid”, “spiderweb” and “hyperbolic grid” profiles were positively associated with higher access to piped water and less overcrowding. The “semi-hyperbolic grid” and “spiderweb” profiles were associated with higher air pollution. The “proximate stones” and “proximate inkblots” profiles were associated with higher congestion. In conclusion, there is substantial heterogeneity in the urban landscape and street design profiles of Latin American cities. While we did not find a specific built environment profile that was consistently associated with lower air pollution and better social conditions, the different configurations of the built environments of cities should be considered when planning healthy and sustainable cities in Latin America.

Background This study examined the variation in city-level amenable mortality, i.e. mortality due to conditions that can be mitigated in the presence of timely and effective healthcare, in 363 Latin American cities and measured associations between amenable-mortality rates and urban metrics. Methods We used death records from 363 cities with populations of >100 000 people in nine Latin American countries from 2010 to 2016. We calculated sex-specific age-adjusted amenable-mortality rates per 100 000. We fitted multilevel linear models with cities nested within countries and estimated associations between amenable mortality and urban metrics, including population size and growth, fragmentation of urban development and socio-economic status. Results Cities in Mexico, Colombia and Brazil had the highest rates of amenable mortality. Overall, >70% of the variability in amenable mortality was due to between-country heterogeneity. But for preventable amenable mortality, those for which the healthcare system can prevent new cases, most of the variability in rates occurred between cities within countries. Population size and fragmentation of urban development were associated with amenable mortality. Higher fragmentation of urban development was associated with lower amenable mortality in small cities and higher amenable mortality in large cities. Population growth and higher city-level socio-economic status were associated with lower amenable mortality. Conclusions Most of the variability in amenable mortality in Latin American cities was due to between-county heterogeneity. However, urban metrics such as population size and growth, fragmentation of urban development and city-level socio-economic status may have a role in the distribution of amenable mortality across cities within countries.

OBJECTIVES: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. METHODS: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. RESULTS: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p

Considering that urban environments may affect self-rated health through behavioral and psychosocial mechanisms, the aim of this study was to investigate the association between self-rated health and perceived urban environment characteristics among adults living in four Latin American cities. Data is from a population-based survey by Development Bank of Latin America, encompassing adults between 20 and 60 years old in Buenos Aires, Lima, Mexico City, and Panama City. Self-rated health was measured using a single question and the response options were categorized as poor and good. The explanatory variables were empirical Bayes estimates of self-reported area physical disorder, social disorder, access to services, and access to leisure spaces derived from the survey. The covariates were: individual age, sex, education, wealth index, and length of residency in the neighborhood, and an area social environment index. Multilevel logistic regressions with two levels (individual and sub-city areas) were fitted. Poor self-rated health was reported by 34.73% (95% CI: 33.17 to 36.29) of the participants and was associated with physical disorder (OR = 1.16 per SD, 95% CI: 1.02 to 1.32). Our findings suggest that public policies to promote population health should consider area urban environment factors, especially those associated with disorder.

Body temperature in tropical forager-farmers declined as much in the past two decades as among Americans in the past 150 years., Normal human body temperature (BT) has long been considered to be 37.0°C. Yet, BTs have declined over the past two centuries in the United States, coinciding with reductions in infection and increasing life expectancy. The generality of and reasons behind this phenomenon have not yet been well studied. Here, we show that Bolivian forager-farmers (n = 17,958 observations of 5481 adults age 15+ years) inhabiting a pathogen-rich environment exhibited higher BT when first examined in the early 21st century (~37.0°C). BT subsequently declined by ~0.05°C/year over 16 years of socioeconomic and epidemiological change to ~36.5°C by 2018. As predicted, infections and other lifestyle factors explain variation in BT, but these factors do not account for the temporal declines. Changes in physical activity, body composition, antibiotic usage, and thermal environment are potential causes of the temporal decline.

Background: Surgical site infections (SSIs) of groin wounds are a common and potentially preventable cause of morbidity, mortality and healthcare costs in vascular surgery. Our aim was to define the contemporaneous rate of groin SSIs, determine clinical sequelae, and identify risk factors for SSI. Method: An international multicentre prospective observational cohort study of consecutive patients undergoing groin incision for femoral vessel access in vascular surgery was undertaken over 3 months, follow up was 90 days. The primary outcome was incidence of groin wound SSI. Results: 1337 groin incisions (1039 patients) from 37 centres were included. 115 groin incisions (8.6%) developed SSI, of which 62 (4.6%) were superficial. Patients who developed an SSI had a significantly longer length of hospital stay (6 vs 5 days, p=0.005), a significantly higher rate of post-operative acute kidney injury (19.6% vs 11.7%, p=0.018), with no significant difference in 90-day mortality. Female sex, Body Mass Index≥30kg/m2, ischaemic heart disease, aqueous betadine skin preparation, bypass/patch use (vein, xenograft or prosthetic) and increased operative time were independent predictors of SSI. Conclusion: Groin infections which are clinically apparent to the treating vascular unit are frequent and their development carries significant clinical sequelae. Risk factors include modifiable and non-modifiable variables.

To describe the characteristics of deaths due to COVID-19 in the state of Rondônia.This was a descriptive study, with data from the Brazilian National Health System Epidemiological Surveillance System Computerization Strategy (E-SUS-VE, notified between January 1 and August 20, 2020. Statistical tests (Chi-square and Marascuilo procedure) were applied, where differences were considered to be significant when p0.05.184,146 suspected cases were reported, of which 49,804 were confirmed as COVID-19, and 1,020 died (lethality 2.1%). Statistically significant differences were observed between age groups and lethality (p-value0.001); lethality was greater as age increased (Marascuilo procedure, significant in the comparison between the over 60s and the other age groups); death was higher among males (2.7% lethality); and lethality was higher among Black people (3.0%).Lethality was greater among the elderly, males and people of brown and black skin color in Rondônia.Descrever as características dos óbitos por COVID-19 no estado de Rondônia.Estudo descritivo, com dados do Sistema Estratégia de Informatização do Sistema Único de Saúde Vigilância Epidemiológica (E-SUS-VE), notificados entre 1º de janeiro e 20 de agosto de 2020. Foram aplicados testes estatísticos (qui-quadrado e procedimento de Marascuilo), considerando-se como diferenças significantes quando os testes apresentaram p-valor0,05.Foram notificados 184.146 casos suspeitos, dos quais 49.804 foram confirmados como COVID-19, e 1.020 evoluíram para óbito (letalidade 2,1%). Observaram-se diferenças significantes estatisticamente entre as faixas etárias e a letalidade (p-valor0,001); maior letalidade quanto maior a idade (procedimento de Marascuilo, significativo na comparação entre maiores de 60 anos com as demais faixas etárias); maior óbito no sexo masculino (letalidade de 2,7%); e maior letalidade entre as pessoas de cor preta (3,0%).Em Rondônia, observou-se maior letalidade entre idosos, homens e pessoas pardas e pretas.Describir las características de los óbitos debidos a COVID-19 en Rondônia.Estudio descriptivo, con datos del Sistema de Estrategia de Computación del Sistema Unificado de Salud de Vigilancia Epidemiológica (E-SUS-VE), notificados entre el 1 de enero y el 20 de agosto de 2020. Se aplicaron pruebas estadísticas (procedimiento Chi-cuadrado y Marascuilo), considerando significativas cuando las pruebas presentaron valor p0,05.se notificaron 184.146 casos sospechosos, con 49.804 confirmados como COVID-19 y 1.020 muertes (letalidad 2,1%). Se observaron diferencias estadísticamente significativas entre grupos de edad y letalidad (valor p0,001); a mayor edad mayor letalidad (procedimiento de Marascuilo, significativo en la comparación entre mayores de 60 años con los otros grupos de edad); mayor óbito en el sexo masculino (letalidad del 2,7%); y mayor letalidad entre la raza negra (3,0%).En Rondônia, hubo una mayor letalidad entre los adultos mayores, hombres y pardos y negros.

This study sought to determine whether adolescents' e-cigarette risk perceptions, perceived benefits, and positive expectations, and vaping behavior changed after the electronic-cigarette or vaping product use-associated lung injury (EVALI) outbreak. This longitudinal survey studied 1539 high school students in suburban Philadelphia, PA in 11th and 12th grade, before and after the outbreak of EVALI cases in 2019. Adolescents who reported current nicotine vaping at baseline (versus those who did not) had a greater increase in risk perceptions (B = -0.31, p = 0.04) and a greater decrease in positive expectations (B = -1.30, p = 0.003) at follow-up. Adolescents who reported current marijuana vaping at baseline (versus those who did not) had greater perceived benefits (B = 2.19, p 0.001), lower risk perceptions (B = 0.39, p 0.001), and greater positive expectations of e-cigarette use (B = 1.43, p 0.001) across time. Odds of current nicotine vaping at follow-up increased (OR = 1.61, 95% CI = 1.08, 2.41) for adolescents who maintained lower risk perceptions. Odds of current nicotine vaping at follow-up decreased (OR = 0.33, 95% CI = 0.21, 0.50) for adolescents whose positive expectations of e-cigarette use decreased. The odds of current marijuana vaping at follow-up decreased (OR = 0.64, 95% CI = 0.42, 0.98) for adolescents whose positive expectations of e-cigarette use decreased. Perceptions of the risks of e-cigarette use increased and positive expectations of e-cigarette use decreased after the EVALI outbreak. Adolescent risk perceptions and positive expectations of e-cigarette use are two potential targets to impact vaping behavior. Emphasizing the risks of e-cigarette use while decreasing positive expectations of use have the potential to reduce vaping behavior, and perhaps subsequent EVALI cases.

Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ-loaded poly(lactic-co-glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U-87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ-loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317-2324, 2019.

The aim of this study was to evaluate the parameters that affect the production of the recombinant 10 kDa culture filtrate protein (CFP10), a promising reagent of high specificity for intradermoreaction and other antigen-based methods used in the diagnosis of tuberculosis. Conditions of Escherichia coli growth temperature, induction temperature and IPTG-inducer concentration were evaluated in shake flasks and dissolved O2 concentrations of 15 and 30% were evaluated in a bioreactor. The process parameters defined on small scale were: growth temperature between 30 and 37 °C, induction temperature of 26 °C and IPTG concentration of 0.12 mM. The process conducted with 15% dissolved O2 presented a recombinant protein yield of 78.6 mg g−1 biomass and a proportion of recombinant protein (insoluble fraction) in relation to total insoluble protein of 72%, at the time of maximum productivity. The operation with 30% dissolved O2 resulted in lower recombinant protein yields of 62.9 mg g−1 biomass and 20% in relation to total insoluble protein, but in higher overall concentration in the culture broth (69.2 mg L−1 versus 48.3 mg L−1). The protein identity was confirmed by mass spectrometry, showing high similarity to CFP10, 10 kDa of Mycobacterium tuberculosis H37Rv (score 95), and the purified antigen presented reactivity by the Western blotting assay.

Summary Indigenous communities worldwide share common features that make them especially vulnerable to the complications of and mortality from COVID-19. They also possess resilient attributes that can be leveraged to promote prevention efforts. How can indigenous communities best mitigate potential devastating effects of COVID-19? In Bolivia, where nearly half of all citizens claim indigenous origins, no specific guidelines have been outlined for indigenous communities inhabiting native communal territories. In this Public Health article, we describe collaborative efforts, as anthropologists, physicians, tribal leaders, and local officials, to develop and implement a multiphase COVID-19 prevention and containment plan focused on voluntary collective isolation and contact-tracing among Tsimane forager-horticulturalists in the Bolivian Amazon. Phase 1 involves education, outreach, and preparation, and phase 2 focuses on containment, patient management, and quarantine. Features of this plan might be exported and adapted to local circumstances elsewhere to prevent widespread mortality in indigenous communities.

BACKGROUND: Road-traffic injuries are a key cause of death and disability in low-income and middle-income countries, but the effect of city characteristics on road-traffic mortality is unknown in these countries. The aim of this study was to determine associations between city-level built environment factors and road-traffic mortality in large Latin American cities. METHODS: We selected cities from Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Panama, and Peru; cities included in the analysis had a population of at least 100 000 people. We extracted data for road-traffic deaths that occurred between 2010 and 2016 from country vital registries. Deaths were grouped by 5-year age groups and sex. Road-traffic deaths were identified using ICD-10 codes, with adjustments for ill-defined codes and incomplete registration. City-level measures included population, urban development, street design, public transportation, and social environment. Associations were estimated using multilevel negative binomial models with robust variances. FINDINGS: 366 cities were included in the analysis. There were 328 408 road-traffic deaths in nearly 3·5 billion person-years across all countries, with an average crude rate of 17·1 deaths per 100 000 person-years. Nearly half of the people who died were younger than 35 years. In multivariable models, road-traffic mortality was higher in cities where urban development was more isolated (rate ratio [RR] 1·05 per 1 SD increase, 95% CI 1·02-1·09), but lower in cities with higher population density (0·94, 0·90-0·98), higher gross domestic product per capita (0·96, 0·94-0·98), and higher intersection density (0·92, 0·89-0·95). Cities with mass transit had lower road mortality rates than did those without (0·92, 0·86-0·99). INTERPRETATION: Urban development policies that reduce isolated and disconnected urban development and that promote walkable street networks and public transport could be important strategies to reduce road-traffic deaths in Latin America and elsewhere. FUNDING: Wellcome Trust.

This longitudinal study described park usage and assessed the contribution of parks to moderate to vigorous physical activity (MVPA) among adolescent girls. High school girls from California (n = 131) and Minnesota (n = 134) wore a global positioning system (GPS) monitor and accelerometer for 6 consecutive days at two time points, one year apart. Park visits were classified by linking the GPS, accelerometer, and park and built environment data around home and school locations into a geographic information system. At baseline, 20% of girls visited a park at least once (mean 0.1 times/day), which was similar one year later (19%, mean 0.1 times/day). Girls lived a mean Euclidean distance of 0.2 miles to the nearest park at both times. Among all park visits, the mean Euclidean distance of the park visited was 4.1 (baseline) and 3.9 miles (follow-up). The average duration of park visits was higher at baseline (63.9 minutes) compared to follow-up (38.4 minutes). On days when a park was visited, MVPA was higher than on days when a park was not visited. On average, 1.9% (baseline) and 2.8% (follow-up) of MVPA occurred in parks. In this study, parks were an under-used resource for adolescent girls, particularly for MVPA.

Researchers have linked neighborhood food availability to the overall frequency of using food outlets without noting if those outlets were within or outside of participants’ neighborhoods. We aimed to examine the association of neighborhood restaurant and food store availability with frequency of use of neighborhood food outlets, and whether such an association was modified by neighborhood street connectivity using a large and diverse population-based cohort of middle-aged U.S. adults. We used self-reported frequency of use of fast food restaurants, sit-down restaurants, and grocery stores in respondents’ home neighborhoods using data from the Coronary Artery Risk Development in Young Adults study Year 20 exam in 2005–2006 (n = 2860; Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) and geographically matched GIS-measured neighborhood-level food resource, street, and U.S. Census data. We used mixed-effects logistic regression to examine the associations of the GIS-measured count of neighborhood fast food restaurants, sit-down restaurants, and grocery stores with self-reported frequency of using neighborhood restaurants and food stores and whether such associations differed by GIS-measured neighborhood street connectivity among those who perceived at least one such food outlet. In multivariate analyses, we observed a positive association between the GIS-measured count of neighborhood sit-down restaurants (OR = 1.02, 95% CI 1.00–1.04) and the self-reported frequency of using neighborhood sit-down restaurants. We observed no statistically significant association between GIS-measured count of neighborhood fast food restaurants and self-reported frequency of using neighborhood fast food restaurants, nor did we observe a statistically significant association between GIS-measured count of neighborhood grocery stores and self-reported frequency of using neighborhood grocery stores. We observed inverse associations between GIS-measured neighborhood street connectivity and the self-reported frequencies of using neighborhood fast food restaurants (OR = 0.42, 95% CI 0.26–0.68) and grocery stores (OR = − 2.26, 95% CI − 4.52 to − 0.01). Neighborhood street connectivity did not modify the association between GIS-measured neighborhood restaurant and food store count and the self-reported frequency of using neighborhood restaurants and food stores. Our findings suggest that, for those who perceived at least one sit-down restaurant in their neighborhood, individuals who have more GIS-measured sit-down restaurants in their neighborhoods reported more frequent use of sit-down restaurants than those whose neighborhoods contain fewer such restaurants. Our results also suggest that, for those who perceived at least one fast food restaurant in their neighborhood, individuals who live in neighborhoods with greater GIS-measured street connectivity reported less use of neighborhood fast food restaurants than those who live in neighborhoods with less street connectivity. The count of neighborhood sit-down restaurants and the connectivity of neighborhood street networks appear important in understanding the use of neighborhood food resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11524-019-00412-x) contains supplementary material, which is available to authorized users.

The concept of a so-called urban advantage in health ignores the possibility of heterogeneity in health outcomes across cities. Using a harmonized dataset from the SALURBAL project, we describe variability and predictors of life expectancy and proportionate mortality in 363 cities across nine Latin American countries. Life expectancy differed substantially across cities within the same country. Cause-specific mortality also varied across cities, with some causes of death (unintentional and violent injuries and deaths) showing large variation within countries, whereas other causes of death (communicable, maternal, neonatal and nutritional, cancer, cardiovascular disease and other noncommunicable diseases) varied substantially between countries. In multivariable mixed models, higher levels of education, water access and sanitation and less overcrowding were associated with longer life expectancy, a relatively lower proportion of communicable, maternal, neonatal and nutritional deaths and a higher proportion of deaths from cancer, cardiovascular disease and other noncommunicable diseases. These results highlight considerable heterogeneity in life expectancy and causes of death across cities of Latin America, revealing modifiable factors that could be amenable to urban policies aimed toward improving urban health in Latin America and more generally in other urban environments.

Importance Almost two-thirds of adolescents who smoke blunts also report using cigars. Although adolescent co-use of blunts and cigars is prevalent, whether adolescent blunt use is associated with progression to current cigar use (past 30-day use) and increased frequency of use is unknown. Objective To determine whether adolescent use of blunts is associated with progression to cigar use (past 30-day use) and increased number of days used (in the past 30 days) across the subsequent 24 months compared with adolescents who have never used blunts. Design, Setting, and Participants In this prospective cohort study of adolescents from 4 public high schools outside of Philadelphia, Pennsylvania, in-classroom surveys were administered at baseline (fall 2016, beginning of 9th grade) and at 6-month intervals for the following 24 months (fall 2018, beginning of 11th grade). Data analyses were conducted in September and October 2019. Exposures Self-report of lifetime (ever) blunt use at baseline (age 14 years). Main Outcomes and Measures Progression to current cigar use (use in the past 30 days) and escalation in the frequency of use (number of days used in the past 30 days) across the subsequent 24 months. Results Of 1825 participants, 907 (49.7%) were female, 1330 (72.9%) were white, and 376 (20.6%) were Hispanic; the mean (SD) age at baseline was 14.38 (0.55) years. In all, 257 participants (14.0%) reported ever blunt use. Mixed-effects models revealed that ever blunt use at baseline vs never blunt use was associated with progression to current cigar use (past 30 days use: odds ratio, 22.66; 95% CI, 11.34-45.27) but not escalation in the number of days used across the following 24 months (β = 0.13; 95% CI, −0.17 to 0.43). Conclusions and Relevance These findings highlight the risk that blunt use may pose for subsequent cigar use among adolescents. Policies and public health campaigns addressing marijuana as well as cigars will be important to reduce adolescent blunt use and cigar use.

INTRODUCTION: Standard care interventions to reduce children’s tobacco smoke exposure (TSE) may not be sufficient to promote behavior change in underserved populations. A previous study demonstrated short-term efficacy of an experimental counseling intervention, “Family Rules for Establishing Smokefree Homes (FRESH)” compared with standard care on boosting low-income children’s TSE reduction and maternal smoking at 16-week end of treatment (EOT). This study tested long-term post-treatment efficacy of this treatment through 12-month follow-up. STUDY DESIGN: This study was a two-arm RCT. SETTING/PARTICIPANTS: Maternal smokers (N=300) not seeking cessation treatment were recruited from low-income, urban communities. Participants exposed their