7,498 research outputs found
The horizon of pediatric cardiac critical care.
Pediatric Cardiac Critical Care (PCCC) is a challenging discipline where decisions require a high degree of preparation and clinical expertise. In the modern era, outcomes of neonates and children with congenital heart defects have dramatically improved, largely by transformative technologies and an expanding collection of pharmacotherapies. Exponential advances in science and technology are occurring at a breathtaking rate, and applying these advances to the PCCC patient is essential to further advancing the science and practice of the field. In this article, we identified and elaborate on seven key elements within the PCCC that will pave the way for the future
Preventive audiology
This book is an original scholarly book that introduces the concept of preventive audiology, with a specific focus on the African context, which is in line with the South African re-engineered primary healthcare strategy as well as the World Health Organisation’s approach. The book reflects on contextually relevant and responsive evidence-based perspectives, grounded in an African context on preventive audiology, in four major ear and hearing burdens of disease within the South African context: (1) early hearing detection and intervention, (2) middle ear pathologies, (3) ototoxicity, and (4) noise-induced hearing loss. The book represents innovative research, seen from both a South African and global perspective. It offers new discourse and argues for a paradigm shift in how audiology is theorised and performed, particularly in low-and-middle-income country contexts. The goal of this book is to motivate a paradigm shift in how the ear and hearing care is approached within this low-and-middle-income country context while arguing for Afrocentric best practice evidence that leads to next practice
Comparison of congenital cardiac surgery techniques through the development of national and international cohorts
Plusieurs avancées exceptionnelles ont permis à un nombre grandissant d’enfants avec pathologies cardiaques complexes d’atteindre l’âge adulte. Ainsi, plus de patients développent maintenant des complications en lien avec leur maladie ou leurs antécédents chirurgicaux. Malheureusement, en raison de nombreux obstacles limitant la recherche en cardiopathie congénitale adulte, un écart de savoir perdure et freine l’optimisation des soins. En attendant le couplage de grands registres pédiatriques et adultes facilitant l’accès aux données existantes, les projets multicentriques indépendants demeurent essentiels. Cette thèse présente deux études multicentriques de cohorte comparant des techniques opératoires couramment utilisées dans le traitement de pathologies congénitales cardiaques complexes dans le but de promouvoir la santé des patients à long terme.
La première étude visait à évaluer l’impact chronique du type de procédure de Fontan sur le risque thromboembolique. Pour ce projet nord-américain, 522 patients avec connexion atriopulmonaire (21.4%), tunnel latéral (41.8%) ou conduit extracardiaque (36.8%) ont été recrutés. À l’aide d’analyses multivariées contrôlant pour la décennie opératoire et les effets variables dans le temps de l’arythmie et de la thromboprophylaxie, l’étude a conclu à un plus faible risque de complications thromboemboliques systémiques (rapport des risques instantanés [RRI] : 0.20 ; intervalle de confiance [IC] à 95% : 0.04-0.97) et combinées (RRI : 0.34 ; IC à 95% : 0.13-0.91) avec le conduit extracardiaque. Ces résultats remettent en question la croyance populaire selon laquelle cette technique serait plus thrombogène en raison d’un grand contact avec du matériel synthétique et d’un débit limité par le calibre fixe du greffon.
La deuxième étude avait pour but d’investiguer, auprès de patients avec tétralogie de Fallot ou sténose pulmonaire corrigée nécessitant une implantation de valve pulmonaire, l’efficacité immédiate et l’innocuité d’une intervention concomitante sur la valve tricuspide. Pour ce projet pancanadien, 542 patients ayant subi un remplacement isolé de la valve pulmonaire (66.8%) ou une chirurgie combinée des valves pulmonaire et tricuspide (33.2%) ont été enrôlés. À l’aide d’analyses multivariées, cette étude a révélé que la chirurgie combinée était associée à une plus grande réduction du grade de régurgitation tricuspidienne qu’un remplacement isolé de la valve pulmonaire (rapport de cotes [RC] : 0.44 ; IC à 95% : 0.25-0.77) sans une augmentation des complications périopératoires (RC : 0.85 ; IC à 95% : 0.46-1.57) ou du temps d’hospitalisation (ratio du taux d’incidence : 1.17 ; IC à 95% : 0.93-1.46). Ces résultats questionnent la pertinence d’une gestion conservatrice de l’insuffisance tricuspide sévère. De plus, ils confirment qu’une procédure ciblée peut améliorer de façon sécuritaire la fuite modérée au-delà de l’effet produit par la décharge du ventricule – une stratégie potentiellement avantageuse auprès de jeunes patients déjà à haut risque de défaillance cardiaque droite.
En conclusion, avec une puissance statistique plus élevée que les études précédemment publiées, ces travaux ont permis une comparaison valide et pertinente de techniques opératoires couramment utilisées en chirurgie cardiaque congénitale, ce qui influencera possiblement la pratique. Ultimement, cette thèse souligne l’importance de promouvoir la collaboration afin de répondre aux besoins émergents des patients avec pathologies congénitales cardiaques complexes.Outstanding technical advances have made possible for a growing number of infants with complex heart disease to survive into adulthood. Consequently, more patients are now living long enough to experience late complications related to their underlying pathology or sequelae from past interventions. However, due to the inherent challenges of carrying research in adult congenital heart disease, important knowledge gaps prevent further optimization of care. Waiting on broad linkage of pediatric and adult databases to facilitate access to data, stand-alone multicenter research initiatives remain essential. The current body of work presents two multicenter cohort studies which were designed to help improving the long-term health of patients with complex heart disease through a comparison of common operative techniques.
The first study sought to evaluate the chronic impact of Fontan surgery type on the thromboembolic risk. This North American cohort enrolled 522 patients with univentricular palliation consisting of an atriopulmonary connection (21.4%), lateral tunnel (41.8%) or extracardiac conduit (36.8%). In multivariable analyses stratified by surgical decade and controlling for the time-varying effects of atrial arrhythmias and thromboprophylaxis, extracardiac conduits were independently associated with a lower risk of systemic (hazard ratio [HR]: 0.20 vs. lateral tunnel; 95% confidence interval [CI]: 0.04-0.97) and combined (HR: 0.34 vs. lateral tunnel; 95% CI: 0.13-0.91) thromboembolic events. These results cast doubt on the widely held notion that extracardiac conduits are potentially more thrombogenic than lateral tunnels by virtue of greater exposure to synthetic material and relative flow restriction through a fixed pathway.
The second study investigated, in patients with repaired tetralogy of Fallot or equivalent disease undergoing a first pulmonary valve implant, the early effectiveness and safety of concomitant tricuspid valve intervention. This pan-Canadian cohort included 542 patients who underwent isolated pulmonary valve replacement (66.8%) or combined pulmonary and tricuspid valve surgery (33.2%). In multivariable analyses, combined surgery was associated with a greater reduction in tricuspid regurgitation grade than isolated pulmonary valve replacement (odds ratio [OR]: 0.44; 95% CI: 0.25-0.77) without an increase in early adverse events (OR: 0.85; 95% CI: 0.46-1.57) or hospitalization time (incidence rate ratio: 1.17; 95% CI: 0.93-1.46). These results strongly question the appropriateness of conservative management of severe tricuspid regurgitation at the time of pulmonary reintervention. Furthermore, they confirm that concomitant tricuspid valve intervention can safely improve moderate insufficiency beyond the effect of right ventricular offloading – a strategy likely worthwhile to adopt in a population of young adults already at high risk of right heart failure.
In conclusion, with higher statistical power than previously published studies, the presented body of work allowed for a valid comparison of common surgical techniques used in congenital cardiac care, which will likely impact current practices. Ultimately, this thesis underlines the importance of fostering collaboration in order to meet the emerging health needs of patients with complex heart disease
Gene Expression Analysis in Cardiac and Adipose Derived Fibroblasts: potential influence of origin and in vitro culture
Cardiac fibroblasts represent one major cell population in the heart, and are responsible for many important cardiac functions. They also arise from different cardiac lineages, suggesting that they are primed to transdifferentiation, and may be directly involved in cardiogenesis.
The objective of this study was to achieve a detailed analysis of the transcriptional activity of human cardiac fibroblasts, derived from right and left atrium, assuming a possible contribution of the fibroblast population in cardiac development.
Cardiac samples were collected, both from adult patients, suffering from coronary and valvular heart disease, and from infant patients suffering from congenital heart disease. Control fibroblasts from adipose tissue, of the same patient, were cultured as a reference. Gene expression was evaluated by reverse transcriptase quantitative polymerase chain reaction (RTqPCR), and subsequently subjected to data analysis. The gene expression was compared between cardiac, and adipose-derived fibroblasts. In addition, the results were analysed according to age, and different cell passages.
Gene expression comparison between atrial cardiac fibroblasts (CF) and their respective adipose tissue fibroblasts (AF), show that certain cardiac transcription factors, such as GATA5, are only expressed in CFs and absent in AFs. Only in children, the same occurs for GATA4 and WT1. However, typical fibroblast markers like CD90 or DDR2, seem to have a higher expression level in AFs. Age-dependent effects are small if any. Passage 0 (P0) fibroblasts, usually show higher gene expression levels than passage 2 (P2) fibroblasts.
Interestingly, in vitro cell culture appears to affect gene expression. Therefore, it is important to use unbiased approaches for gene expression analysis such as directly use ex vivo purified cardiac fibroblasts. Further gene expression studies, focused on diagnoses, may contribute togene interference in cell culture differences. The eventual possibility of using fibroblasts in cardiac regeneration strongly encourages further research in this area
Recent Applications of Three Dimensional Printing in Cardiovascular Medicine
Three dimensional (3D) printing, which consists in the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced a rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest growing area for medical 3D printing. In this review, we firstly describe the major steps and the most common technologies used in the 3D printing process, then we present current applications of 3D printing with relevance to the cardiovascular field. The technology is more frequently used for the creation of anatomical 3D models useful for teaching, training, and procedural planning of complex surgical cases, as well as for facilitating communication with patients and their families. However, the most attractive and novel application of 3D printing in the last years is bioprinting, which holds the great potential to solve the ever-increasing crisis of organ shortage. In this review, we then present some of the 3D bioprinting strategies used for fabricating fully functional cardiovascular tissues, including myocardium, heart tissue patches, and heart valves. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro cardiovascular drug toxicity. Finally, we describe some applications of 3D printing in the development and testing of cardiovascular medical devices, and the current regulatory frameworks that apply to manufacturing and commercialization of 3D printed products
Trends in Pharmaceutical and Food Sciences I
Podeu consultar el llibre complet a: https://medwinpublishers.com/OAJPR/OAJPR16000eB001.pdfTrends in Pharmaceutical and Food Sciences I is the first issue of an open access E-book devoted to scientific and technical research that covers the entire spectrum of drug and food research, including medicinal chemistry, pharmacology, drug delivery, microbiology and biochemical studies, as well as relevant developments in nutrition, food safety and analytical innovation.
The first chapter, Different techniques to detect G protein coupled receptor heteromers, describes state of the art techniques based in biophysical principles applied to detect oligomeric aggregates formed by G-protein coupled receptors in the cell membrane, and describes how the knowledge generated can be applied to design new compounds for the treatment of neurological and mental diseases.
Obesity has become a worldwide problem and it is well known that causes and exacerbates many health problems by promoting profound changes in physiological functions.
Chapter 2, Analysis of the role of diet in the appearance of neurodegenerative processes, reviews the consequences of these metabolic alterations while considering their effects in the development of Type 2 Diabetes Mellitus, and their role in the appearance of cognitive impairments such as the sporadic forms of Alzheimer’s disease.
The development of new cultivars facing climate change is an issue of great interest for the agrochemical industry and can be approached in different ways.
Chapter 3, Arabidopsis Thaliana A Model for the Study of Plant Speciation, reviews different aspects of the plant immune system and the different layers of the plant immune response and signaling. The emerging field in plant research that studies how soil microbiota influences plant basic mechanisms is also discussed.
Chagas disease is endemic in Latin America, but recently and due to human migrations, it is becoming a global health problem.
In chapter 4, Trypanosoma cruzi infection diagnosis: New insights, challenges and perspectives, a group of experts from
several institutions describe the different techniques that can be used for the serological diagnosis of the infection and the
characterization of Trypanosoma cruzi, discuss the advantages and drawbacks of each method and propose improvements that
would entail important savings for health institutions.
Chapter 5, Nutrients, Control of Gene Expression and Metabolic Homeostasis, focuses on the molecular mechanisms that control metabolism by means of regulating gene expression in response to dietary inputs, to design new therapeutic strategies based on nutritional interventions against metabolic diseases. In this context, involvement of FGF21 hormone in the regulation of lipid metabolism during amino acid starvation is described, thus reinforcing its important role as an endocrine factor in coordinating energy homeostasis under a variety of nutritional conditions. This raises the possibility of dietary modulation of circulating levels of FGF21 as an alternative approach to its pharmacological administration.
Biodegradable polymeric nanoparticles encapsulating neuroprotective drugs have enormous potential to treat neurodegenerative diseases, including Alzheimer´s disease and glaucoma. Recent advances in the field are described in chapter 6, Polymeric nanoparticles for the treatment of neurodegenerative diseases: Alzheimer’s disease and glaucoma, specifically the preparation of engineered polymeric nanoparticles with attached peptides or antibodies to increase their bioavailability, favoring their transport through the blood brain barrier and the blood retinal barrier, avoiding at the same time possible drug adverse and toxic effects.
The last chapter, Pentacyclic triterpenes in table olives: Determination of their composition and bioavailability by LC-M, is a review on the pentacyclic triterpenes contained in table olives, natural compounds of enormous interest due to their beneficial effects on human health, including hepatoprotective, anti-diabetic, antiviral, cardioprotective and antitumor activities.
Authors describe a selective and sensitive LC–MS method for the simultaneous determination of the main triterpenic compounds present in Olea europaea L. This opens the possibility to bioavailability studies after consumption of different foods, or administration of plants widely used in traditional medicine, with the aim of studying in depth the beneficial effects of these compounds in human beings.
We hope that this new volume will attract the interest of all the scientific community, especially those working in the fields of pharmaceutical, medical, biological, chemical and food sciences
Dosage Compensation of Trisomy 21 and Its Implications for Hematopoietic Pathogenesis in Down Syndrome
Down Syndrome (DS), the most common aneuploidy seen in live-borns, is caused by trisomy for chromosome 21. DS imposes high risks for multiple health issues involving various systems of the body. The genetic complexity of trisomy 21 and natural variation between all individuals has impeded understanding of the specific cell pathologies and pathways involved. In addition, chromosomal disorders have been considered outside the hopeful progress in gene therapies for single-gene disorders. Here we test the feasibility of correcting imbalanced expression of genes across an extra chromosome by expression of a single gene, XIST, the key player in X chromosome inactivation. We targeted a large XIST transgene into one chromosome 21 in DS iPS cells, and demonstrated XIST RNA spreads and induces heterochromatin and gene silencing across that autosome in cis.
By making XIST inducible, this allows direct comparison of effects of trisomy 21 expression on cell function and phenotypes. Importantly, XIST-induction during in vitro hematopoiesis normalized excess production of differentiated blood cell types (megakaryocytes and erythrocytes), known to confer high risk for myeloproliferative disorder and leukemia. In contrast, trisomy silencing enhances production of iPS and neural stem cells, consistent with DS clinical features. Further analysis revealed that trisomy 21 initially impacts the endothelial hematopoietic transition (EHT) to generate excess CD43+ progenitors, and also increases their colony forming potential. Furthermore, results provide evidence for a key role for enhanced IGF signaling, involving over-expression of non-chromosome 21 genes controlled by trisomy 21. Finally, experiments to examine trisomy effects on angiogenesis showed no effect on production of endothelial cells, but it remains unclear whether trisomic cells may differ in ability to form vessels.
Collectively, this thesis demonstrates proof-of-principle for XIST-mediated “trisomy silencing”. Phenotypic improvement of hematopoietic and neural stem cells demonstrates the value for research into DS pathogenesis, but also provides a foundation of potential for future development of “chromosome therapy” for DS patients
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