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Using zinc (Zn) foliar fertilizers to enhance the grain quality of wheat (Triticum aestivum) can be an effective alternative or supplement to Zn soil fertilizers. However, knowledge about the mechanisms of Zn absorption and translocation following foliar application is scarce. Here, autoradiography and γ-spectrometry were used to investigate the behavior of 65Zn applied to wheat leaves as soluble 65Zn chloride (65ZnCl2), chelated 65Zn (65ZnEDTA), 65Zn oxide nanoparticle (65ZnO-NP) suspensions, and 65ZnO microparticle (65ZnO-MP) suspensions. The largest amount of 65Zn absorption occurred in 65ZnCl2 treated leaves. However, this treatment (65ZnCl2) also had the lowest proportion of absorbed 65Zn translocated away from the treated leaf after 15 d due to leaf scorching (p = 0.0007). Foliar-applied 65ZnO-NPs and 65ZnO-MPs had the lowest absorption, but 65ZnO-NPs had the highest relative translocation. 65Zinc EDTA was intermediate, with higher 65Zn absorption than 65ZnO treatments but similar translocation. Regardless, the majority of the foliar-applied 65Zn remained in the treated leaf for all treatments. Furthermore, 65ZnO-NPs and 65ZnO-MPs accumulated in plant nodes, suggesting that Zn was absorbed as dissolved 65Zn and particulate 65ZnO. Overall, the form and amount of absorbed 65Zn affected translocation.
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Nanopartículas , Óxido de Zinco , Grão Comestível/química , Fertilizantes/análise , Folhas de Planta/química , Solo , Triticum , Zinco/análiseRESUMO
OBJECTIVE: Integrating behavioral health services into the primary care setting is a recognized approach to improving timely access and building capacity for primary care providers. The aim of this study was to examine barriers to family medicine resident learning in a co-located primary care-behavioral health integration program with psychiatrists in an academic hospital. METHODS: The authors used a descriptive qualitative study design to collect data on participants' learning experiences from focus groups and semi-structured interviews with 5 family medicine residents, 3 psychiatry residents, 5 family physicians, 3 psychiatrists, 2 office coordinators, and 2 educational coordinators. Thematic analysis of transcripts was performed. RESULTS: Three themes were identified with respect to barriers to learning in the program from the family medicine perspective. Organizational barriers encompassed lack of clear vision, goals, roles, and responsibilities. Administrative barriers involved complex appointment bookings and scheduling. Communication and engagement barriers included insufficient communication between team members and lack of patient engagement in the program. CONCLUSIONS: The study findings highlight the importance of several factors for the successful implementation of a co-located academic primary care-behavioral health integrated model. This includes the formalization of program structure that encompasses shared vision, goals, roles, and responsibilities; coordinated processes for appointment bookings; team communication and patient engagement; and diverse educational and longitudinal care opportunities. With the growing number of integrated care programs, these results provide guidance for health care leaders involved in the design and management of primary care-behavioral health integration programs.
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Medicina de Família e Comunidade , Pessoal de Saúde , Hospitais Universitários , Relações Interprofissionais , Serviços de Saúde Mental , Atenção Primária à Saúde , Adulto , Medicina de Família e Comunidade/educação , Medicina de Família e Comunidade/organização & administração , Medicina de Família e Comunidade/normas , Pessoal de Saúde/educação , Pessoal de Saúde/organização & administração , Pessoal de Saúde/normas , Hospitais Universitários/organização & administração , Hospitais Universitários/normas , Humanos , Capacitação em Serviço , Internato e Residência , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/normas , Médicos de Família/educação , Atenção Primária à Saúde/organização & administração , Atenção Primária à Saúde/normas , Psiquiatria/educação , Pesquisa QualitativaRESUMO
BACKGROUND: Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research. METHODS: A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics. RESULTS: We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis. CONCLUSION: There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.
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Interpretação Estatística de Dados , Modificador do Efeito Epidemiológico , Pesquisa sobre Serviços de Saúde/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Atenção à Saúde/métodos , Atenção à Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodos , Modelos de Riscos Proporcionais , Análise de Sobrevida , Fatores de TempoRESUMO
The degree to which an individual accumulates evidence prior to making a decision, also known as reflection impulsivity, can be affected in psychiatric disorders. Here, we study decisional impulsivity in binge drinkers, a group at elevated risk for developing alcohol use disorders, comparing two tasks assessing reflection impulsivity and a delay discounting task, hypothesizing impairments in both subtypes of impulsivity. We also assess volumetric correlates of reflection impulsivity focusing on regions previously implicated in functional magnetic resonance imaging studies. Sixty binge drinkers and healthy volunteers were tested using two different information-gathering paradigms: the beads task and the Information Sampling Task (IST). The beads task was analysed using a behavioural approach and a Bayesian model of decision making. Delay discounting was assessed using the Monetary Choice Questionnaire. Regression analyses of primary outcomes were conducted with voxel-based morphometry analyses. Binge drinkers sought less evidence prior to decision in the beads task compared with healthy volunteers in both the behavioural and computational modelling analysis. There were no group differences in the IST or delay discounting task. Greater impulsivity as indexed by lower evidence accumulation in the beads task was associated with smaller dorsolateral prefrontal cortex and inferior parietal volumes. In contrast, greater impulsivity as indexed by lower evidence accumulation in the IST was associated with greater dorsal cingulate and precuneus volumes. Binge drinking is characterized by impaired reflection impulsivity suggesting a deficit in deciding on the basis of future outcomes that are more difficult to represent. These findings emphasize the role of possible therapeutic interventions targeting decision-making deficits.
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Consumo Excessivo de Bebidas Alcoólicas/psicologia , Tomada de Decisões/fisiologia , Comportamento Impulsivo/fisiologia , Estudos de Casos e Controles , Simulação por Computador , Desvalorização pelo Atraso/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tamanho do Órgão/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2ß-carbomethoxy-3ß-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. METHODS: The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. RESULTS: Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. CONCLUSIONS: Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.
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Corpo Estriado/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologia , Estudos de Casos e Controles , Corpo Estriado/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Cintilografia , TropanosRESUMO
Contaminants, including naturally occurring radioactive material (NORM) of the 238-uranium and 232-thorium decay series, have been recognized as a global research priority to inform offshore petroleum infrastructure decommissioning decisions. This study aimed to characterize pipeline scale retrieved from a decommissioned subsea well tubular pipe through high-resolution elemental mapping and isotopic analysis. This was achieved by utilizing transmission electron microscopy, Synchrotron x-ray fluorescence, photostimulated luminescence autoradiography and Isotope Ratio Mass Spectrometry. The scale was identified as baryte (BaSO4) forming a dense crystalline matrix, with heterogenous texture and elongated crystals. The changing chemical and physical microenvironment within the pipe influenced the gradual growth rate of baryte over the production life of this infrastructure. A distinct compositional banding of baryte and celestine (SrSO4) bands was observed. Radioactivity attributed by the presence of radionuclides (226Ra, 228Ra) throughout the scale was strongly correlated with baryte. From the detailed scale characterization, we can infer the baryte scale gradually formed within the internals of the tubular well pipe along the duration of production (i.e., 17 years). This new knowledge and insight into the characteristics and formation of petroleum waste products will assist with decommissioning planning to mitigate potential radiological risks to marine ecosystems.
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PURPOSE: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs). METHODS AND MATERIALS: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil. RESULTS: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 109 n/cm2/Gy (relative biological effectiveness) for the carbon beam and 5.8 × 109 n/cm2/Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions. CONCLUSIONS: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.
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Carbono , Sobrevivência Celular , Glioblastoma , Hélio , Imagens de Fantasmas , Hélio/uso terapêutico , Humanos , Glioblastoma/radioterapia , Glioblastoma/patologia , Sobrevivência Celular/efeitos da radiação , Linhagem Celular Tumoral , Carbono/uso terapêutico , Radioterapia com Íons Pesados/métodos , Terapia por Captura de Nêutron/métodos , Nêutrons/uso terapêutico , Dosagem Radioterapêutica , Terapia por Captura de Nêutron de Boro/métodos , Boro/uso terapêutico , Polimetil Metacrilato , IsótoposRESUMO
DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the L-glutamine moiety were synthesised and labelled with 67,68Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available 67Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced 68Ga was in the [68Ga(OH)4]â» form. The 67Ga complexes and the 67Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived 67Ga analogues against four tumour cell lines, as well as uptake inhibition studies against L-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway.
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Radioisótopos de Gálio/química , Glutamina/química , Glutamina/metabolismo , Compostos Heterocíclicos com 1 Anel/química , Neoplasias/metabolismo , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Glutamina/análogos & derivados , Glutamina/síntese química , Humanos , Marcação por Isótopo , Tomografia por Emissão de Pósitrons , Traçadores Radioativos , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismoRESUMO
OBJECTIVE: Car dependency contributes to physical inactivity and, consequently, may increase the likelihood of diabetes. We investigated whether neighborhoods that are highly conducive to driving confer a greater risk of developing diabetes and, if so, whether this differs by age. RESEARCH DESIGN AND METHODS: We used administrative health care data to identify all working-age Canadian adults (20-64 years) who were living in Toronto on 1 April 2011 without diabetes (type 1 or 2). Neighborhood drivability scores were assigned using a novel, validated index that predicts driving patterns based on built environment features divided into quintiles. Cox regression was used to examine the association between neighborhood drivability and 7-year risk of diabetes onset, overall and by age-group, adjusting for baseline characteristics and comorbidities. RESULTS: Overall, there were 1,473,994 adults in the cohort (mean age 40.9 ± 12.2 years), among whom 77,835 developed diabetes during follow-up. Those living in the most drivable neighborhoods (quintile 5) had a 41% higher risk of developing diabetes compared with those in the least drivable neighborhoods (adjusted hazard ratio 1.41, 95% CI 1.37-1.44), with the strongest associations in younger adults aged 20-34 years (1.57, 95% CI 1.47-1.68, P < 0.001 for interaction). The same comparison in older adults (55-64 years) yielded smaller differences (1.31, 95% CI 1.26-1.36). Associations appeared to be strongest in middle-income neighborhoods for younger residents (middle income 1.96, 95% CI 1.64-2.33) and older residents (1.46, 95% CI 1.32-1.62). CONCLUSIONS: High neighborhood drivability is a risk factor for diabetes, particularly in younger adults. This finding has important implications for future urban design policies.
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Diabetes Mellitus , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Canadá , Estudos de Coortes , Renda , Fatores de Risco , Características de ResidênciaRESUMO
The RGD (Arg-Gly-Asp) binding integrins α(v)ß(3) and α(IIb)ß(3) are integral components of various pathological and physiological processes, including tumor angiogenesis, osteoclast function, and thrombus formation. Because of this, there is interest in identifying novel compounds and proteins binding to these receptors as well as investigating the mechanism of these interactions. In this article, we describe the development and validation of competition binding assays for determining the affinity of test compounds to α(v)ß(3) and α(IIb)ß(3) integrin. Assays were successfully developed for each receptor, and the affinity of known compounds was comparable to published results. However, the inability of binding between α(IIb)ß(3) integrin and the labeled echistatin protein ligand to reach equilibrium resulted in an assay that did not meet the assumptions of the competition binding model. Nevertheless, there was good agreement between this assay and known literature values, and intra- and interassay variability was acceptable. Binding by conformation-specific antibodies provided evidence that solid-phase bound α(IIb)ß(3) receptor was in an activated conformation. This study also demonstrated that current models and methods for determining receptor affinity are simplistic and fail to account for common receptor-ligand interactions such as nondissociable interactions and varying receptor activation states.
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Ligação Competitiva , Bioensaio/métodos , Integrina alfaVbeta3/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Biotinilação , Linhagem Celular Tumoral , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Marcação por Isótopo , Cinética , Oligopeptídeos/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Reprodutibilidade dos TestesRESUMO
In recent decades, the prevalence of obesity and diabetes has risen substantially in North America and worldwide. To address these dual epidemics, researchers and policymakers alike have been searching for effective means to promote healthy lifestyles at a population level. As a consequence, there has been a proliferation of research examining how the "built" environment in which we live influences physical activity levels, by promoting active forms of transportation, such as walking and cycling, over passive ones, such as car use. Shifting the transportation choices of local residents may mean that more members of the population can participate in physical activity during their daily routine without structured exercise programs. Increasingly, this line of research has considered the downstream metabolic consequences of the environment in which we live, raising the possibility that "healthier" community designs could help mitigate the rise in obesity and diabetes prevalence. This review discusses the evidence examining the relationship between the built environment, physical activity, and obesity-related diseases. We also consider how other environmental factors may interact with the built environment to influence metabolic health, highlighting challenges in understanding causal relationships in this area of research.
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Diabetes Mellitus , Planejamento Ambiental , Humanos , Ambiente Construído , Obesidade/epidemiologia , Obesidade/etiologia , Caminhada , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologiaRESUMO
Guillain-Barré syndrome (GBS) is a rare condition caused by autoimmune damage of peripheral nerves. We describe a case where a man in his 80s presented with subacute, progressive fatigue and weakness. He had received an outpatient work-up for possible haematological malignancy, but eventually presented to the emergency department for worsening weakness. A physical exam and cerebrospinal fluid analysis suggested a diagnosis of GBS. Subsequently, a pathological diagnosis of angioimmunoblastic T-cell lymphoma was made. The patient underwent intravenous immunoglobulin treatment for GBS and was started on cyclophosphamide, doxorubicin, vincristine and prednisone therapy. Prior research has suggested that incident malignancy may be associated with GBS, which may be caused by a paraneoplastic-type phenomenon, malignancy-associated immune dysregulation or an autoimmune reaction triggered by a common exposure. Clinicians should be aware of the possible association between these two conditions and should remain open minded to the possibility of non-infectious triggers for GBS.
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Síndrome de Guillain-Barré , Linfoma de Células T , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/etiologia , Humanos , Imunoglobulinas Intravenosas , Linfoma de Células T/complicações , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , MasculinoRESUMO
Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera-from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies.
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Bacteriófagos , Bactéria Gordonia , Bacteriófagos/genética , Genoma Viral , Genômica , Bactéria Gordonia/genética , Humanos , Filogenia , Águas ResiduáriasRESUMO
Here, we characterized the complete genome of the Siphoviridae BiggityBass, a lytic subcluster DR bacteriophage infecting Gordonia terrae CAG3. Its 63.2-kb genome contains 84 protein-coding genes, of which 40 could be assigned a putative function. BiggityBass is related most closely to AnClar and Yago84 with 90.61% and 90.52% nucleotide identity, respectively.
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Shock events uncover deficits in social cohesion and exacerbate existing social inequalities at the household, community, local, regional, and national levels. National and regional government recovery planning requires careful stakeholder engagement that centers on marginalized people, particularly women and marginalized community leaders. The aim of this rapid scoping review was to inform the United Nations Research Roadmap for the COVID-19 Recovery, based on Pillar 5 of the United Nations Framework for the Immediate Socioeconomic Response to COVID-19: Social Cohesion and Community Resilience. We present a summary of key concepts across the literature that helped situate this review. The results include a description of the state of the science and a review of themes identified as being crucial to sustainable and equitable recovery planning by the United Nations. The role of social cohesion during a disaster, particularly its importance for upstream planning and relationship building before a disaster occurs, is not well understood and is a promising area of future research. Understanding the applicability of social cohesion measurement methodologies and outcomes across different communities and geographies, as well as the development of new and relevant instruments and techniques, is urgently needed in the context of the global COVID-19 pandemic.
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COVID-19/epidemiologia , Comportamento Cooperativo , Resiliência Psicológica , Capital Social , Participação da Comunidade , Relações Comunidade-Instituição , Saúde Global , Humanos , Pandemias , Características de Residência , SARS-CoV-2 , Fatores Socioeconômicos , Nações UnidasRESUMO
Background: During the COVID-19 pandemic, many urban residents stopped riding public transit despite their reliance on it to reach essential services like healthcare. Few studies have examined the implications of public transit reliance on riders' ability to reach healthcare when transit is disrupted. To understand how shocks to transportation systems impact healthcare access, this study measures the impact of avoiding public transit on the ability of riders to access healthcare and pharmacy services during lockdowns. Methods: We deployed a cross-sectional survey of residents of Toronto and Vancouver in May 2020 through Facebook advertisements and community list-serves. Eligibility criteria included riding transit at least weekly prior to the pandemic and subsequent cessation of transit use during the pandemic. We applied multivariable modified Poisson models to identify socio-demographic, transportation, health-related, and neighborhood predictors of experiencing increased difficulty accessing healthcare and getting prescriptions while avoiding public transit. We also predicted which respondents reported deferring medical care until they felt comfortable riding transit again. Results: A total of 4367 former transit riders were included (64.2% female, 56.1% Toronto residents). Several factors were associated with deferring medical care including: being non-White (Toronto, APR, 1.14; 95% CI, 1.00-1.29; Vancouver, APR, 1.52; 95% CI, 1.26-1.84), having a physical disability (Toronto, APR, 1.20; 95% CI, 1.00-1.45; Vancouver, APR, 1.42; 95% CI, 1.08-1.87), having no vehicle access (Toronto, APR, 1.74; 95% CI, 1.51-2.00; Vancouver, APR, 2.74; 95% CI, 2.20-3.42), and having low income (Toronto, APR, 1.77; 95% CI, 1.44-2.17; Vancouver, APR, 1.51; 95% CI, 1.06-2.14). Discussion: During COVID-19 in two major Canadian cities, former transit riders from marginalized groups were more likely to defer medical care than other former riders. COVID-19 related transit disruptions may have imposed a disproportionate burden on the health access of marginalized individuals. Policymakers should consider prioritizing healthcare access for vulnerable residents during crises.
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The brain's early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain's vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain's intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo +/+) and TSPO knockout (Tspo -/-) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo-/- and Tspo +/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain's vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration.
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In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.
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Background Individuals living in unwalkable neighborhoods appear to be less physically active and more likely to develop obesity, diabetes mellitus, and hypertension. It is unclear whether neighborhood walkability is a risk factor for future cardiovascular disease. Methods and Results We studied residents living in major urban centers in Ontario, Canada on January 1, 2008, using linked electronic medical record and administrative health data from the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) cohort. Walkability was assessed using a validated index based on population and residential density, street connectivity, and the number of walkable destinations in each neighborhood, divided into quintiles (Q). The primary outcome was a predicted 10-year cardiovascular disease risk of ≥7.5% (recommended threshold for statin use) assessed by the American College of Cardiology/American Heart Association Pooled Cohort Equation. Adjusted associations were estimated using logistic regression models. Secondary outcomes included measured systolic blood pressure, total and high-density lipoprotein cholesterol levels, prior diabetes mellitus diagnosis, and current smoking status. In total, 44 448 individuals were included in our analyses. Fully adjusted analyses found a nonlinear relationship between walkability and predicted 10-year cardiovascular disease risk (least [Q1] versus most [Q5] walkable neighborhood: odds ratio =1.09, 95% CI: 0.98, 1.22), with the greatest difference between Q3 and Q5 (odds ratio=1.33, 95% CI: 1.23, 1.45). Dose-response associations were observed for systolic blood pressure, high-density lipoprotein cholesterol, and diabetes mellitus risk, while an inverse association was observed with smoking status. Conclusions In our setting, adults living in less walkable neighborhoods had a higher predicted 10-year cardiovascular disease risk than those living in highly walkable areas.
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Doenças Cardiovasculares/epidemiologia , Características de Residência , Medição de Risco , Caminhada , Pressão Sanguínea , HDL-Colesterol/sangue , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fumar/epidemiologia , Sístole , População UrbanaRESUMO
Individuals' risk for cardiovascular disease is shaped by lifestyle factors such as participation in physical activity. Some studies have suggested that rates of physical activity may be higher in walkable neighborhoods that are more supportive of engaging in physical activity in daily life. However, walkable neighborhoods may also contain increased levels of traffic-related air pollution (TRAP). Traffic-related air pollution, often measured through a surrogate marker (e.g. NO2), has been associated cardiovascular disease risk and risk factors [1], [2], [3], [4]. The higher levels of TRAP in walkable neighborhoods may in turn increase the likelihood of developing conditions like hypertension and diabetes. Our recent work assessed how walkability and TRAP jointly affect the odds of diabetes and hypertension in a sample of community-dwelling adults from Southern Ontario, Canada [5]. This article contains additional data on the probability and odds of hypertension and diabetes according to their walkability and TRAP exposures. Data on cardiovascular risk factors were collected using health administrative databases and environmental exposures were assessed using national land use regression models predicting ground level concentrations of NO2 and validated walkability indices. The included data were generated using logistic regression accounting for exposures, covariates, and neighborhood clustering. These data may be used as primary data in future health risk assessments and systematic reviews, or to aid in the design of studies examining interactions between built environment and TRAP exposures (e.g. sample size calculations).