Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
11,124
result(s) for
"Roland, D"
Sort by:
Epilepsy in adults
Epilepsy is one of the most common serious brain conditions, affecting over 70 million people worldwide. Its incidence has a bimodal distribution with the highest risk in infants and older age groups. Progress in genomic technology is exposing the complex genetic architecture of the common types of epilepsy, and is driving a paradigm shift. Epilepsy is a symptom complex with multiple risk factors and a strong genetic predisposition rather than a condition with a single expression and cause. These advances have resulted in the new classification of epileptic seizures and epilepsies. A detailed clinical history and a reliable eyewitness account of a seizure are the cornerstones of the diagnosis. Ancillary investigations can help to determine cause and prognosis. Advances in brain imaging are helping to identify the structural and functional causes and consequences of the epilepsies. Comorbidities are increasingly recognised as important aetiological and prognostic markers. Antiseizure medication might suppress seizures in up to two-thirds of all individuals but do not alter long-term prognosis. Epilepsy surgery is the most effective way to achieve long-term seizure freedom in selected individuals with drug-resistant focal epilepsy, but it is probably not used enough. With improved understanding of the gradual development of epilepsy, epigenetic determinants, and pharmacogenomics comes the hope for better, disease-modifying, or even curative, pharmacological and non-pharmacological treatment strategies. Other developments are clinical implementation of seizure detection devices and new neuromodulation techniques, including responsive neural stimulation.
Journal Article
Diagnosis and treatment of orthostatic hypotension
Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.
Journal Article
Autonomic manifestations of epilepsy: emerging pathways to sudden death?
Epileptic networks are intimately connected with the autonomic nervous system, as exemplified by a plethora of ictal (during a seizure) autonomic manifestations, including epigastric sensations, palpitations, goosebumps and syncope (fainting). Ictal autonomic changes might serve as diagnostic clues, provide targets for seizure detection and help us to understand the mechanisms that underlie sudden unexpected death in epilepsy (SUDEP). Autonomic alterations are generally more prominent in focal seizures originating from the temporal lobe, demonstrating the importance of limbic structures to the autonomic nervous system, and are particularly pronounced in focal-to-bilateral and generalized tonic–clonic seizures. The presence, type and severity of autonomic features are determined by the seizure onset zone, propagation pathways, lateralization and timing of the seizures, and the presence of interictal autonomic dysfunction. Evidence is mounting that not all autonomic manifestations are linked to SUDEP. In addition, experimental and clinical data emphasize the heterogeneity of SUDEP and its infrequent overlap with sudden cardiac death. Here, we review the spectrum and diagnostic value of the mostly benign and self-limiting autonomic manifestations of epilepsy. In particular, we focus on presentations that are likely to contribute to SUDEP and discuss how wearable devices might help to prevent SUDEP.The close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and diagnostic value of these manifestations, focusing on presentations that could contribute to sudden unexpected death in epilepsy.
Journal Article
Gene-guided discovery and engineering of branched cyclic peptides in plants
The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome mining enabled by this initial finding revealed rich lyciumin genotypes and chemotypes widespread in flowering plants. We establish a biosynthetic framework of lyciumins and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. With rapidly expanding plant genome resources, our approach will complement bioactivity-guided approaches to unlock and engineer hidden plant peptide chemistry for pharmaceutical and agrochemical applications.
Journal Article
Determinants of patient choice of healthcare providers: a scoping review
Background
In several northwest European countries, a demand-driven healthcare system has been implemented that stresses the importance of patient healthcare provider choice. In this study, we are conducting a scoping review aiming to map out what is known about the determinants of patient choice of a wide range of healthcare providers. As far as we know, not many studies are currently available that attempt to draw a general picture of how patients choose a healthcare provider and of the status of research on this subject. This study is therefore a valuable contribution to the growing amount of literature about patient choice.
Methods
We carried out a specific type of literature review known as a scoping review. Scoping reviews try to examine the breadth of knowledge that is available about a particular topic and therefore do not make selections or apply quality constraints. Firstly, we defined our research questions and searched the literature in Embase, Medline and PubMed. Secondly, we selected the literature, and finally we analysed and summarized the information.
Results
Our review shows that patients’ choices are determined by a complex interplay between patient and provider characteristics. A variety of patient characteristics determines whether patients make choices, are willing and able to choose, and how they choose. Patients take account of a variety of structural, process and outcome characteristics of providers, differing in the relative importance they attach to these characteristics.
Conclusions
There is no such thing as the typical patient: different patients make different choices in different situations. Comparative information seems to have a relatively limited influence on the choices made by many patients and patients base their decisions on a variety of provider characteristics instead of solely on outcome characteristics. The assumptions made in health policy about patient choice may therefore be an oversimplification of reality. Several knowledge gaps were identified that need follow-up research.
Journal Article
Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A
Recent developments in next-generation sequencing technologies have brought recognition of microbial genomes as a rich resource for novel natural product discovery. However, owing to the scarcity of efficient procedures to connect genes to molecules, only a small fraction of secondary metabolomes have been investigated to date. Transformation-associated recombination (TAR) cloning takes advantage of the natural in vivo homologous recombination of Saccharomyces cerevisiae to directly capture large genomic loci. Here we report a TAR-based genetic platform that allows us to directly clone, refactor, and heterologously express a silent biosynthetic pathway to yield a new antibiotic. With this method, which involves regulatory gene remodeling, we successfully expressed a 67-kb nonribosomal peptide synthetase biosynthetic gene cluster from the marine actinomycete Saccharomonospora sp. CNQ-490 and produced the dichlorinated lipopeptide antibiotic taromycin A in the model expression host Streptomyces coelicolor. The taromycin gene cluster (tar) is highly similar to the clinically approved antibiotic daptomycin from Streptomyces roseosporus, but has notable structural differences in three amino acid residues and the lipid side chain. With the activation of the tar gene cluster and production of taromycin A, this study highlights a unique \"plug-and-play\" approach to efficiently gaining access to orphan pathways that may open avenues for novel natural product discoveries and drug development.
Journal Article
Changes needed in health information systems to support an ageing population
Health information systems are essential for evidence-based decision-making and must transform to support healthy ageing in rapidly ageing societies. This change requires strengthening of the structures and processes that enable the collection, integration, analysis and use of comprehensive, integrated and person-centred information in health, social and long-term care sectors. Interoperability and governance mechanisms are important to link data and services and ensure coordinated and continuous care for older adults. Health information systems should incorporate ageing-relevant areas such as functional ability, well-being, end-of-life preferences, living environments, informal and formal caregiving, and social determinants of health. Advanced analytics and tools to support decision-making can provide actionable insights to improve the quality of care, evaluate progress and inform the design of age-friendly policies and services. Equally, systems must be user-centred and accessible, adapted to varying levels of digital literacy, and co-designed with older adults and communities. Engaging older adults and communities in the design of health information systems can enhance relevance, equity, trust and uptake. Such systems can support older adults to actively manage their health. Finally, robust ethical and legal frameworks are essential to guide the responsible design, implementation and use of health information systems. These frameworks should safeguard privacy and uphold dignity, particularly concerning sensitive data, informed consent and decision-making capacity in later life.
Journal Article