Project description:Human pain causes untold misery and suffering, with major impact on functioning and resources. Recent advances in genetics have revealed that subtle changes in DNA could partly explain the variation in individual differences in pain. Various genes encoding for receptors are now known to play a major role in the sensitivity, perception and expression of pain. The fields of epigenetics and proteomics hold promises in the way pain could be treated and managed in future.
Project description:IgE-associated food allergy affects approximately 3% of the population and has severe effects on the daily life of patients-manifestations occur not only in the gastrointestinal tract but also affect other organ systems. Birth cohort studies have shown that allergic sensitization to food allergens develops early in childhood. Mechanisms of pathogenesis include cross-linking of mast cell- and basophil-bound IgE and immediate release of inflammatory mediators, as well as late-phase and chronic allergic inflammation, resulting from T-cell, basophil, and eosinophil activation. Researchers have begun to characterize the molecular features of food allergens and have developed chip-based assays for multiple allergens. These have provided information about cross-reactivity among different sources of food allergens, identified disease-causing food allergens, and helped us to estimate the severity and types of allergic reactions in patients. Importantly, learning about the structure of disease-causing food allergens has allowed researchers to engineer synthetic and recombinant vaccines.
Project description:MRI is increasingly used in radiation oncology to facilitate tumor and organ-at-risk delineation and image guidance. In this review, we address issues of MRI that are relevant for radiation oncologists when interpreting MR images offered for radiotherapy. Whether MRI is used in combination with CT or in an MRI-only workflow, it is generally necessary to ensure that MR images are acquired in treatment position, using the positioning and fixation devices that are commonly applied in radiotherapy. For target delineation, often a series of separate image sets are used with distinct image contrasts, acquired within a single exam. MR images can suffer from image distortions. While this can be avoided with dedicated scan protocols, in a diagnostic setting geometrical fidelity is less relevant and is therefore less accounted for. Since geometrical fidelity is of utmost importance in radiation oncology, it requires dedicated scan protocols. The strong magnetic field of an MRI scanner and the use of radiofrequency radiation can cause safety hazards if not properly addressed. Safety screening is crucial for every patient and every operator prior to entering the MRI room.
Project description:OverviewThe use of extracorporeal membrane oxygenation (ECMO) is becoming commonplace worldwide in ICUs for the care of patients with respiratory and/or cardiac failure. Understanding the use of ECMO and the management of these complex patients will be vital to current and future clinicians as ECMO use continues to grow.
Project description:Lightweight concrete has a history of more than two-thousand years and its technical development is still proceeding. This review starts with a retrospective that gives an idea of the wide range of applications covered by lightweight concrete during the last century. Although lightweight concrete is well known and has proven its technical potential in a wide range of applications over the past decades, there are still hesitations and uncertainties in practice. For that reason, lightweight aggregate properties and the various types of lightweight concrete are discussed in detail with a special focus on current standards. The review is based on a background of 25 years of practical and theoretical experience in this field. One of the main challenges in designing lightweight concrete is to adapt most of design, production and execution rules since they often deviate from normal weight concrete. Therefore, aspects are highlighted that often are the cause of misunderstandings, such as nomenclature or the informational value of certain tests. Frequently occurring problems regarding the mix design and production of lightweight concrete are addressed and the unintended consequences are described. A critical view is provided on some information given in existing European concrete standards regarding the mechanical properties of structural lightweight concrete. Finally, the latest stage of development of very light lightweight concretes is presented. Infra-lightweight concrete is introduced as an innovative approach for further extending the range of applications of lightweight concrete by providing background knowledge and experiences from case records.
Project description:Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders.A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions.
Project description:The pathogenesis of inherited cataracts of all kinds recapitulates the developmental and cell biology of the lens. Just as each novel mutation provides additional information about the structural or functional biology of the affected gene, each newly identified gene provides insight into the developmental and cellular biology of the lens. The set of genes currently known to be associated with cataract is far from complete, especially for age-related cataract, and there is much additional information to be discovered through further genetic studies.
Project description:AbstractThere is a growing trend in the world of orthopedics and sports medicine revolving around the nonarthritic hip. The incidence of hip arthroscopy has exponentially grown in the past decade and despite the importance of the recognition of these hip pathologies as contributors to pain and dysfunction, there is an ever-increasing rate of "failed" procedures emerging in the literature. The etiology of femoroacetabular impingement (FAI) syndrome and associated pathologies of the hip are now better understood. With this understanding there appears a tendency to point a finger at the hip joint without consideration for the involvement of the surrounding joints or extraarticular structures. Because of the nature of the morphological condition of FAI and the high incidence of a gradual progression of pain and impairments over time, as opposed to an acute injury, there is a need for a more robust assessment of the hip. The purpose of this commentary is to discuss the importance of a combined traditional orthopedic exam, imaging, and movement assessment in diagnosis and treatment recommendations in those with nonarthritic hip pain. It is our belief that this combined model can assist in identifying movement dysfunction that may lead to poor surgical outcomes and developing improved nonoperative or preoperative care pathways.Level of evidenceLevel V.