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Background and aim: Experimental studies show that short-term exposure to air pollution may alter cytokine concentrations. There is, however, a lack of epidemiological studies evaluating the association between long-term air pollution exposure and inflammation-related proteins in young children. Our objective was to examine whether air pollution exposure is associated with inflammation-related proteins during the first 2 years of life. Methods: In a pooled analysis of two birth cohorts from Stockholm County (n = 158), plasma levels of 92 systemic inflammation-related proteins were measured by Olink Proseek Multiplex Inflammation panel at 6 months, 1 year and 2 years of age. Time-weighted average exposure to particles with an aerodynamic diameter of

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. In animal models, OSA has been shown to alter the gut microbiota; however, little is known about such effects in humans. Here, we used respiratory polygraphy data from 3,570 individuals aged 50–64 from the Swedish CardioPulmonary bioImage Study (SCAPIS) and deep shotgun metagenomics to identify OSA-associated gut microbiota features. We found that OSA-related hypoxia parameters were associated with 128 bacterial species, including positive associations with Blautia obeum and Collinsela aerofacines. The latter was also associated with increased systolic blood pressure. Further, the cumulative time in hypoxia was associated with nine gut microbiota metabolic pathways, including propionate production from lactate, a biomarker of hypoxia. In conclusion, in this first large-scale study on gut microbiota alterations in OSA, we found that OSA-related hypoxia is associated with specific microbiota features. Our findings can direct future research on microbiota-mediated health effects of OSA.

BACKGROUNDGut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis, and to explore relevant clinical correlates.METHODSWe conducted a cross-sectional study of 8973 participants aged 50 to 65 without overt atherosclerotic disease from the population-based Swedish Cardiopulmonary BioImage Study (SCAPIS). Coronary atherosclerosis was measured using coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA). Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool samples, and their association with coronary atherosclerosis was evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTSThe mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3% of participants, and 5.4% had at least one stenosis with more than 50% occlusion. Sixty-four species were associated with CACS independent of cardiovascular risk factors, with the strongest associations observed forStreptococcus anginosusandS. oralissubsp. oralis(P-5). Associations were largely similar across CCTA-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations and 16 with neutrophil counts. Oral species in the gut were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid beta-oxidation and amino acid degradation was associated with CACS.CONCLUSIONSThis study provides evidence of an association of a gut microbiota composition characterized by increased abundance ofStreptococcusspp. and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation. Further longitudinal and experimental studies are warranted to explore the potential implication of a bacterial component in atherogenesis.CLINICAL PERSPECTIVEWHAT IS NEW?Shotgun metagenomics identified associations between gut species and subclinical atherosclerosis assessed with computed tomography-derived coronary artery calcium score (CACS) in 8973 participants, with an overrepresentation of theStreptococcusandOscillobactergenera.The relative abundance of CACS-associated oral species detected in fecal samples was negatively associated with indole propionate, while positively associated with secondary bile acids and imidazole propionate.GutStreptococcusspp. were positively associated with circulating biomarkers of systemic inflammation and infection response, and with the same species located in the mouth, which were in turn associated with oral pathologies.WHAT ARE THE CLINICAL IMPLICATIONS?We describe the link between gut microbiota composition, especially species commonly found in the mouth, with subclinical coronary atherosclerosis and biomarkers of inflammation in the largest cardiovascular and metagenomics study to date.The effects of gut and oralStreptococcusspp. on risk for coronary artery disease merit further longitudinal and experimental studies.

Summary paragraphThe human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota–host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha diversity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of individual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas “GUTSY” as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

Study Objectives Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population-based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. Methods In 2,471 participants (49.7% men, mean age 61.2 ± 8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self-reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using a false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. Results We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. Conclusions In this population-based study, proteins previously related to cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders.

To determine the risk factors for acquiring central line-associated blood stream infections (CLABSI) in pediatric intensive care units and to investigate the incidence and etiology of CLABSI in pediatric intensive care units with different profiles.The study was a prospective cohort study in three hospitals. One of the hospitals is a large metropolitan public hospital with two pediatric intensive care units and a total of nineteen pediatric intensive care unit beds, another is a regional hospital with eight pediatric intensive care unit beds, and the third is a private hospital with fifteen beds. Patients between the ages of 1 month old and 18 years old who used a central venous catheter for over 24 hours were included. We recorded patients' daily progress. General patient and catheter-related data were collected and used as variables. All the data were analyzed using Statistical Package for Social Science (SPSS), version 13.0, to compare patients with CLABSI with or without risk factors.A total of 728 patients were admitted to the pediatric intensive care units, and 170 had a central line in place for at least 24 hours. The median age was 32 months, and 97 (57%) of the patients were males. The CLABSI incidence rate was 3.9/1000 central venous catheter-days. The incidence among hospitals varied from 1.6 to 6.6. The overall mortality rate was 11.1%, and the CLABSI and non-CLABSI mortality rates were 12.9% and 10.7%, respectively. In multivariate analysis, independent risk factors for CLABSI were a longer duration of central venous catheter use (OR: 1.07; 95%CI 1.00 - 1.14; p = 0.019) and the use of more than one central venous catheter at once (OR: 2.59; 95%CI 1.17 - 5.73; p = 0.048).A longer duration of central venous catheter use and the use of more than one central venous catheter at once were the main risk factors for CLABSI in pediatric intensive care units.Determinar os fatores de risco para contrair infecções da corrente sanguínea associadas a cateter de acesso central em unidades de terapia intensiva pediátrica, e investigar a incidência e a etiologia dessas infecções nas unidades de terapia intensiva pediátrica com diferentes perfis.Este foi um estudo prospectivo de coorte, conduzido em três hospitais. Um deles é um grande hospital público metropolitano, com duas unidades de terapia intensiva pediátrica que contabilizam 19 leitos; o segundo é um hospital regional com oito leitos em unidade de terapia intensiva pediátrica; e o terceiro é um hospital privado com 15 leitos de terapia intensiva pediátrica. Incluíram-se pacientes com idades entre 1 mês e 18 anos, que utilizaram cateter de acesso venoso central por pelo menos 24 horas. Registramos a evolução diária dos pacientes. Colheram-se dados gerais sobre o paciente e sobre o cateter, utilizados como variáveis. Todos os dados foram analisados com utilização do pacote estatístico Statistical Package for Social Science (SPSS), versão 13.0, para comparação de pacientes com infecção da corrente sanguínea associada a cateter com ou sem fatores de risco.Durante o período do estudo admitiram-se às unidades de terapia intensiva 728 pacientes; deles, 170 tiveram cateter de acesso venoso central instalado por, no mínimo, 24 horas. A mediana de idade foi de 32 meses, e 97 (57%) dos pacientes eram do sexo masculino. A taxa de incidência de infecções da corrente sanguínea relacionadas a cateter foi de 3,9/1.000 cateteres venosos centrais-dias. A incidência variou entre os hospitais, sendo de 1,6 a 6,6. A taxa geral de mortalidade foi de 11,1%, e as taxas de mortalidade com e sem infecções da corrente sanguínea relacionadas a cateter foram, respectivamente, de 12,9% e 10,7%. Na análise multivariada, os fatores de risco para ocorrência de infecções da corrente sanguínea relacionadas a cateter foram maior tempo de uso do cateter venoso central (OR: 1,07; IC95% 1,00 - 1,14; p = 0,019) e o uso de mais de um cateter venoso central de uma vez (OR: 2,59; IC95% 1,17 - 5,73; p = 0,048).Maior duração do uso de cateter venoso central e mais de um cateter venoso central de uma vez foram os principais fatores de risco para infecções da corrente sanguínea associadas a cateter em unidades de terapia intensiva pediátrica.

Objectives: In sickle cell/β-thalassemia, mutations in the corresponding β-globin genes are responsible for complex pathological events resulting in diverse clinical complications. The objective of this study was to provide an overview of the clinical and laboratory characteristics of patients with the syndrome, and of the degree of severity of clinical manifestations resulting from the β-thalassemia mutation.Methods: A retrospective chart review was performed on 46 patients with sickle cell/β-thalassemia (31 Sβ° and 15 Sβ+), evaluating hematological parameters and end organ damage. Statistical analyzes were carried out in order to highlight differences between the two groups according to the nature of the thalassemia mutation.Results: As expected, patients with the Sβ0 phenotype had a higher degree of hematological involvement in comparison to Sβ+ patients; with lower hemoglobin levels, and signs of more intense chronic hemolysis. However, Sβ+ patients were more prone to the occurrence of acute chest syn...

In sickle cell/β-thalassemia, mutations in the corresponding β-globin genes are responsible for complex pathological events resulting in diverse clinical complications. The objective of this study was to provide an overview of the clinical and laboratory characteristics of patients with the syndrome, and of the degree of severity of clinical manifestations resulting from the β-thalassemia mutation.A retrospective chart review was performed on 46 patients with sickle cell/β-thalassemia (31 Sβ° and 15 SβAs expected, patients with the SβThis study identified significant differences among sickle cell/β-thalassemia patients according to the beta mutation involvement, pointing to an important predictor of disease severity.

OBJECTIVES: To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION: Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease. METHODS: Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses. RESULTS: In total, 65 patients were included in this study: 12 (18.5%) with normal bone mass density, 37 (57%) with osteopenia and 16 (24.5%) with osteoporosis. Overall, 53 patients (81.5%) had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p