: Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue ...damage and an alteration of arterial structure and function. Increased arterial stiffness is a well recognized cardiovascular risk factor independent of blood pressure levels and an intermediate endpoint for cardiovascular events. In the present review, we discuss immune-mediated mechanisms by which inflammation can influence arterial physiology and lead to vascular dysfunction such as atherosclerosis and arterial stiffening. We also show that acute inflammation predisposes the vasculature to arterial dysfunction and stiffening, and alteration of endothelial function and that chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis are accompanied by profound arterial dysfunction which is proportional to the severity of inflammation. Current findings suggest that treatment of inflammation by targeted drugs leads to regression of arterial dysfunction. There is hope that these treatments will improve outcomes for patients.
Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), ...Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).
Microfluidics evolved with the appearance of polydimethylsiloxane (PDMS), an elastomer with a short processing time and the possibility for replication on a micrometric scale. Despite the many ...advantages of PDMS, there are well-known drawbacks, such as the hydrophobic surface, the absorption of small molecules, the low stiffness, relatively high cost, and the difficulty of scaling up the fabrication process for industrial production, creating a need for alternative materials. One option is the use of stiffer thermoplastics, such as the cyclic olefin copolymer (COC), which can be mass produced, have lower cost and possess excellent properties. In this work, a method to fabricate COC microfluidic structures was developed. The work was divided into process optimization and evaluation of material properties for application in microfluidics. In the processing step, moulding, sealing, and liquid handling aspects were developed and optimized. The resulting COC devices were evaluated from the point of view of molecular diffusion, burst pressure, temperature resistance, and susceptibility to surface treatments and these results were compared to PDMS devices. Lastly, a target DNA hybridization assay was performed showing the potential of the COC-based microfluidic device to be used in biosensing and Lab-on-a-Chip applications.
Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past ...decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA‐ADHD and ENIGMA‐ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA‐ADHD and ‐ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case–control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case–control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow‐up analyses continue that include more imaging modalities (diffusion MRI and resting‐state functional MRI), collaborations with other large databases, and samples with dual diagnoses.
The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we ...aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference −2.1 ms, 95% confidence interval −12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.
Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies suggest a role for indigenous microbiota in the course of this pathology. Therefore, the aim of our ...study was to evaluate the differences in phenotype between germ-free (GF) and conventional (CV) mice, and the role of β-glucuronidase-producing bacteria in the development of irinotecan treatment in a murine model. After mucositis induction, CV mice showed a significant increase in all inflammatory parameters when compared to GF mice. CV animals also showed more lesions of the intestinal epithelium, coherent with their higher intestinal permeability. The conventionalization of GF animals reversed their phenotype to that found in CV mice. In addition, gnotobiotic mice monoassociated with an Escherichia coli strain producing β-glucuronidase showed an increased permeability when compared to gnotobiotic mice monoassociated with an E. coli strain deleted for the gene encoding β-glucuronidase, but these did not show any differences in the influx of neutrophils, eosinophils or histological characteristics. Our data confirmed that components of the gut microbiota are involved in the signs of mucositis. Nevertheless, other mechanisms than this enzyme are involved in the irinotecan treatment, since the monoassociation was not able to restore the entire phenotype observed in the CV animals with irinotecan treatment in our murine model.
Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with ...major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.
The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T
-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1.
The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.
Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.
Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, ...there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners.
This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course.
The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n=67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n=97); University of São Paulo (Brazil) (n=64); University of Cantabria, Santander (Spain) (n=107); and University of Melbourne (Australia) (n=54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either “continuous” (n=94) or “remitting” (n=118).
Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p<0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples.
This study provides proof of concept that combining multi-center MRI data to create a well performing classification model is possible. However, to create complex multi-center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single-center.
•Multi-center neuroimaging data can be combined to classify clear biological outcome.•Classification is only significant in centers with similar illness outcome definition.•Multi-center models can increase performance of smaller and heterogeneous samples.•Multi-center studies should use large samples and standardized clinical information.•Multi-center models have the potential to yield clinically useful predictions.
The Atlantic bonito (Sarda sarda, family Scombridae) is a pelagic species and one of the most exploited small tuna species. Despite its economic importance, biological information is scarce with no ...associated management directives. In this study, using a population genomic approach resulted in a lack of panmixia of two genetic pools with different effective population sizes (east central-tropical Atlantic and northeast Atlantic-Mediterranean) and an intermixing zone in Atlantic Morocco. The absence of genetic heterogeneity between the locations in Atlantic - Mediterranean transitional zone adds new evidence that challenges the Strait of Gibraltar as a phylogeographic barrier for marine pelagic species. These results are proposed to the ICCAT Commission to establish management areas for this species, although they are not consistent with the recently adopted pelagic ecoregions. Finally, a panel of highly informative SNPs was developed for efficient and low-cost population assignment and the analysis of unresolved population structures.
•The Atlantic bonito is one of the most exploited small tuna species with lack of knowledge of the population structure.•Population genomic anlysis resulted in lack of panmixia of two pools in Atlantic – Med and intermixing in Atlantic Morocco.•Lack of heterogeneity in the Atlantic - Med transitional zone challenges the Strait of Gibraltar as a phylogeographic barrier.•These results are proposed to establish management areas for this species.
The last four decades have witnessed tremendous growth in research studies applying neuroimaging methods to evaluate pathophysiological and treatment aspects of psychiatric disorders around the ...world. This article provides a brief history of psychiatric neuroimaging research in Brazil, including quantitative information about the growth of this field in the country over the past 20 years. Also described are the various methodologies used, the wealth of scientific questions investigated, and the strength of international collaborations established. Finally, examples of the many methodological advances that have emerged in the field of in vivo neuroimaging are provided, with discussion of the challenges faced by psychiatric research groups in Brazil, a country of limited resources, to continue incorporating such innovations to generate novel scientific data of local and global relevance.
PDF
