1,721,066 research outputs found
Genetic diagnosis in neonatal-onset epilepsies: Back to the future
No full textSeizures are more frequent in newborns than in any other period of life. In most cases they are due to acute dysfunction of the central nervous system; however some can be true epileptic disorders with an early onset. Although rare, diagnosis of neonatal-onset epilepsies is rising as genetic testing increases. The spectrum of clinical severity associated with specific genes can vary widely with difficulties in providing genotype–phenotype correlations. Therefore, clinicians should strive in order to clearly delineate the clinical features associated with pathogenic genetic variants with the aim to guide the increasing use of genetic testing and improve clinical management
Genetic neonatal-onset epilepsies and developmental/epileptic encephalopathies with movement disorders: A systematic review
Full text linkDespite expanding next generation sequencing technologies and increasing clinical in-terest into complex neurologic phenotypes associating epilepsies and developmental/epileptic encephalopathies (DE/EE) with movement disorders (MD), these monogenic conditions have been less extensively investigated in the neonatal period compared to infancy. We reviewed the medical literature in the study period 2000–2020 to report on monogenic conditions characterized by neonatal onset epilepsy and/or DE/EE and development of an MD, and described their electroclinical, genetic and neuroimaging spectra. In accordance with a PRISMA statement, we created a data collection sheet and a protocol specifying inclusion and exclusion criteria. A total of 28 different genes (from 49 papers) leading to neonatal-onset DE/EE with multiple seizure types, mainly featuring tonic and myoclonic, but also focal motor seizures and a hyperkinetic MD in 89% of conditions, with neonatal onset in 22%, were identified. Neonatal seizure semiology, or MD age of onset, were not always available. The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants. The outcome is characterized by high rates of associated neurodevelopmental disorders and microcephaly. Brain MRI findings are either normal or nonspecific in most conditions, but serial imaging can be necessary in order to detect progressive abnormalities. We found high genetic heterogeneity and low numbers of described patients. Neurological phenotypes are complex, reflecting the involvement of genes necessary for early brain development. Future studies should focus on accurate neonatal epileptic phenotyping, and detailed description of semiology and time-course, of the associated MD, especially for the rarest conditions
OrphanAnesthesia - A common project of the Scientific Working Group of Paediatric Anaesthesia of the German Society of Anaesthesiology and Intensive Care Medicine
No full textThe target of OrphanAnesthesia is the publication of anaesthesia recommendations for patients suffering from rare diseases in order to improve patients' safety. When it comes to the management of patients with rare diseases, there are only sparse evidencebased facts and even far less knowledge in the anaesthetic outcome. OrphanAnesthesia would like to merge this knowledge based on scientific publications and proven experience of specialists making it available for physicians worldwide free of charge. All OrphanAnesthesia recommendations are standardized and need to pass a peer review process. They are being reviewed by at least one anaesthesiologist and another disease expert (e.g. paediatrician or neurologist) involved in the treatment of this group of patients. The project OrphanAnesthesia is internationally oriented. Thus all recommendations will be published in English. Starting with issue 5/2014, we'll publish the OrphanAnesthesia recommenations as a monthly supplement of A&I (Anästhesiologie & Intensivmedizin). Thus they can be accessed and downloaded via www.aionline.info. As being part of the journal, the recommendations will be quotable. Reprints can be ordered for payment
Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of colon cancer
No full textThe use of biomarkers to assess cancer risk is based on the model of cancer as a multistep process; such markers are assumed to reflect an early stage in this process. A valid biomarker of risk must therefore show differential expression in normal and high-risk subjects, as well as quantitative correlation with the stage of carcinogenesis. It should also be easy to detect in small tissue specimens and responsive to modulation by chemopreventive agents. Cell proliferation is one of the most widely investigated markers of cancer risk. Case-control studies have shown that epithelial cell proliferation parameters, assessed in rectal mucosal biopsies by means of in vitro autoradiographic or immunohistochemical techniques, can discriminate between populations with normal and high risks for colon cancer. However, we recently reviewed rectal biopsies from 152 subjects (43 controls, 84 with adenomas, 25 resected for colon cancer) processed for in vitro 3H-thymidine autoradiography, and attempted to correlate various proliferative parameters with clinical and pathological variables by means of multiple regression analysis. Elevations of total crypt labeling indices (LIs), particularly upper crypt LIs, were significantly associated with the presence of adenomatous polyps, although subsequent linear discriminant analysis revealed that the accuracy of LIS in discriminating between polyp patients and controls was actually quite low. However, we have also found that upper crypt LIs are reliable predictors of adenomatous polyp recurrence. Repeated evaluations of rectal proliferative indices over a 2-year post-polypectomy follow-up of 40 patients with colonic adenomas revealed substantial stability. We have also shown that, although circadian variation occurs, it is confined to the normal proliferative zone in the lower crypt, with upper crypt proliferation remaining quite stable. These proliferative indices have been shown to respond to chemopreventive agents (dietary and chemical), and we have recently shown that the improvements obtained with ω-3 fatty-acid supplementation persist during long-term treatment. Although definitive validation of the rectal epithelial cell proliferation biomarker has not yet been achieved, recent prospective studies have shown parallel effects by putative chemopreventive agents on cell proliferation and precursor lesions of colorectal cancer
Mismatch repair genes founder mutations and cancer susceptibility in Lynch syndrome
No full textFounder mutations in specific populations are common in several Mendelian disorders. They are shared by apparently unrelated families that inherited them from a common ancestor that existed hundreds to thousands of years ago. They have been proven to impact in molecular diagnostics strategies in specific populations, where they can be assessed as the first screening step and, if positive, avoid further expensive gene scanning. In Lynch syndrome (LS), a dominantly inherited colorectal cancer disease, more than 50 founder pathogenic mutations have been described so far in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2). We here provide a comprehensive summary of the founder mutations found in the MMR genes and an overview of their main characteristics. At a time when high-throughput strategies are being introduced in the molecular diagnostics of cancer, genetic testing for founder mutations can complement next generation sequencing (NGS) technologies to most efficiently identify MMR gene mutations in any given population. Additionally, special attention is paid to MMR founder mutations with interesting anthropological significance
ANCA-Associated Vasculitis
No full textANCA-associated vasculitis (AAV) is a group of disorders characterized by inflammation affecting small blood vessels. AAV includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). AAV can be considered a complex disease; in fact, both genetic and environmental factors are involved in its susceptibility. To improve the understanding of the disease, the genetic component has been extensively studied by candidate-gene and genome-wide association studies. Most of the identified genetic AAV risk factors are common variants, whose functional importance still needs further investigation. In this chapter, we discuss the results of genetic studies in AAV. We also present novel approaches to identify the causal variants in complex susceptibility loci and disease mechanisms. Finally, we discuss the challenges in translating genomic data into clinical practice
Liquid biopsy with cell free DNA: new horizons for prostate cancer
No full textAlthough prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years. Due to the high variability of the scientific methods adopted and a lack of standardized median cfDNA levels, results fluctuate across different studies. These differences may be due to the cfDNA source, the quantification method, or the fragmentation pattern. Blood plasma is the most frequently analyzed biological fluid, but seminal plasma has been reported to contain higher cfDNA concentration due to its vicinity to the tumor origin. CfDNA has been shown to be composed of single-stranded (ssDNA) and double-stranded DNA (dsDNA), so the total cfDNA concentration should be preferred as it corresponds best to the tumor mass. Fluorometry and capillary electrophoresis (CE) may be quick and cost-effective tools for cfDNA assessment in a clinical setting. The greatest future challenge is the elaboration of common guidelines and standardized procedures for diagnostic laboratories performing cfDNA analysis. A multiparametric approach combining the analysis of total cfDNA (both ssDNA and dsDNA), cfDNA fragment length, and specific genetic mutations (ctDNA assessment) is required for optimal future applications of liquid biopsy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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