Diagnostic Considerations in the Epilepsies-Testing Strategies, Test Type Advantages, and Limitations.
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ABSTRACT:
SUBMITTER: Chen WL
PROVIDER: S-EPMC8608977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Amid revolutionary changes in toxicity assessment brought about by increasing regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful framework to assess adverse effect of chemicals using molecular level effect, which aid in setting environmental regulation policies. AOPs are biological maps that describe mechanisms linking molecular initiating event to adverse outcomes (AOs) at an individual level. Each AOP consists of a molecular initiating event, key events, and an AO. AOPs use molecular markers to predict endpoints currently used in risk assessment, promote alternatives to animal model-based test methods, and provide scientific explanations for the effects of chemical exposures. Moreover, AOPs enhance certainty in interpreting existing and new information. The application of AOPs in chemical toxicity testing will help shift the existing paradigm of chemical management based on apical endpoints toward active application of in silico and in vitro data.
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Project description:Premature ejaculation (PE) is the most common male sexual dysfunction worldwide. Characteristic symptoms of PE are unexpected, rapid, complete ejaculation, which negatively impacts the sexual act for both sexual partners. Despite the existence of a definitive PE classification system and various diagnostic tools, diagnosing PE is still challenging due to the limitations associated with the assessment of this condition. Hence, it is necessary to review the diagnostic methods and processes of the physical examination that are currently performed in the medical setting. It is also important to analyze any controversial results of each main PE assessment method and propose novel diagnostic and assessment methods. To date, it is important to verify the accuracy of the PE evaluation method due to the ambiguity of previous definitions and proven invalidity of current examining techniques. Clinical diagnosis is based mainly on the patient history, patient-reported outcome scores, and diagnostic tools. Introduction of intravaginal ejaculatory latency time, penile biothesiometry, and the electrophysiological test provided objective means of evaluating PE. Due to the controversial and inconclusive findings in PE psychogenic and neurogenic etiology, utilizing a single parameter to describe and qualify PE using the aforementioned diagnostic methods provides valuable, but insufficient information for PE diagnosis. There is still a lack of a feasible and plausible means of objective measurement to evaluate the ejaculatory latency and control over ejaculation. Consequently, a comprehensive penile stimulation that simulates sexual intercourse could be useful to record intensity and duration parameters before the ejaculatory threshold, providing a more accurate method of describing and diagnosing PE versus a single chronological observation.
| S-EPMC7215025 | biostudies-literature
Project description:This review outlines the design strategies which aim to develop high performing n-type materials in the fields of organic thin film transistors (OTFT), organic electrochemical transistors (OECT) and organic thermoelectrics (OTE). Figures of merit for each application and the limitations in obtaining these are set out, and the challenges with achieving consistent and comparable measurements are addressed. We present a thorough discussion of the limitations of n-type materials, particularly their ambient operational instability, and suggest synthetic methods to overcome these. This instability originates from the oxidation of the negative polaron of the organic semiconductor (OSC) by water and oxygen, the potentials of which commonly fall within the electrochemical window of n-type OSCs, and consequently require a LUMO level deeper than ∼-4 eV for a material with ambient stability. Recent high performing n-type materials are detailed for each application and their design principles are discussed to explain how synthetic modifications can enhance performance. This can be achieved through a number of strategies, including utilising an electron deficient acceptor-acceptor backbone repeat unit motif, introducing electron-withdrawing groups or heteroatoms, rigidification and planarisation of the polymer backbone and through increasing the conjugation length. By studying the fundamental synthetic design principles which have been employed to date, this review highlights a path to the development of promising polymers for n-type OSC applications in the future.
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Project description:Detection of neuronal surface antibodies (NSAb) is important for the diagnosis of autoimmune encephalitis (AE). Although most clinical laboratories use a commercial diagnostic kit (Euroimmun, Lübeck, Germany) based on indirect immunofluorescence on transfected cells (IIFA), clinical experience suggests diagnostic limitations. Here, we assessed the performance of the commercial IIFA in serum and CSF samples of patients with suspected AE previously examined by rat brain immunohistochemistry (Cohort A). Of 6213 samples, 404 (6.5%) showed brain immunostaining suggestive of NSAb: 163 (40%) were positive by commercial IIFA and 241 (60%) were negative. When these 241 samples were re-assessed with in-house IIFA, 42 (18%) were positive: 21 (9%) had NSAb against antigens not included in the commercial IIFA and the other 21 (9%) had NSAb against antigens included in the commercial kit (false negative results). False negative results occurred more frequently with CSF (29% vs 10% in serum) and predominantly affected GABABR (39%), LGI1 (17%) and AMPAR (11%) antibodies. Results were reproduced in a separate cohort (B) of 54 AE patients with LGI1, GABABR or AMPAR antibodies in CSF which were missed in 30% by commercial IIFA. Patients with discordant GABABR antibody results (positive in-house but negative commercial IIFA) were less likely to develop full-blown clinical syndrome; no significant clinical differences were noted for the other antibodies. Overall, NSAb testing by commercial IIFA led to false negative results in a substantial number of patients, mainly those affected by anti-LG1, GABABR or AMPAR encephalitis. If these disorders are suspected and commercial IIFA is negative, more comprehensive antibody studies are recommended.
| S-EPMC8276168 | biostudies-literature
Project description:Microsatellite instability (MSI), a common alteration in endometrial cancers (EC) is known as a biomarker for immune checkpoint therapy response alongside screening for Lynch Syndrome (LS). However, former studies described challenging MSI profiles in EC hindering analysis by using MSI testing methods intensively validated for colorectal cancer (CRC) only. In order to reduce false negatives, this study examined four different PCR-based approaches for MSI testing using 25 EC samples already tested for mismatch repair deficiency (dMMR). In a follow up validation set of 75 EC samples previously tested both for MMR and MSI, the efficiency of a seven-marker system corresponding to the Idylla system was further analyzed. Both Bethesda and Promega marker panels require trained operators to overcome interpretation complexities caused by either hardly visible additional peaks of one and two nucleotides, or small shifts in microsatellite repeat length. Using parallel sequencing adjustment of bioinformatics is needed. Applying the Idylla MSI assay, an evaluation of input material is more crucial for reliable results and is indispensable. Following MMR deficiency testing as a first-line screening procedure, additional testing with a PCR-based method is necessary if inconclusive staining of immunohistochemistry (IHC) must be clarified.
| S-EPMC8000432 | biostudies-literature
Project description:During early post-natal life, neonates must adjust to the transition from the sheltered intra-uterine environment to the microbe-laden external world, wherein they encounter a constellation of antigens and the colonization by the microbiome. At this vulnerable stage, neonatal immune responses are considered immature and present significant differences to those of adults. Pertinent to innate immunity, functional and quantitative deficiencies in antigen-presenting cells and phagocytes are often documented. Exposure to environmental antigens and microbial colonization is associated with epigenetic immune cell reprogramming and activation of effector and regulatory mechanisms that ensure age-depended immune system maturation and prevention of tissue damage. Moreover, neonatal innate immune memory has emerged as a critical mechanism providing protection against infectious agents. Still, in neonates, inexperience to antigenic exposure, along with enhancement of tissue-protective immunosuppressive mechanisms are often associated with severe immunopathological conditions, including sepsis and neurodevelopmental disorders. Despite significant advances in the field, adequate vaccination in newborns is still in its infancy due to elemental restrictions associated also with defective immune responses. In this review, we provide an overview of neonatal innate immune cells, highlighting phenotypic and functional disparities with their adult counterparts. We also discuss the effects of epigenetic modifications and microbial colonization on the regulation of neonatal immunity. A recent update on mechanisms underlying dysregulated neonatal innate immunity and linked infectious and neurodevelopmental diseases is provided. Understanding of the mechanisms that augment innate immune responsiveness in neonates may facilitate the development of improved vaccination protocols that can protect against pathogens and organ damage.
| S-EPMC6997472 | biostudies-literature
Project description:BackgroundThe implementation of evidence-based guidelines can improve clinical and public health outcomes by helping health professionals practice in the most effective manner, as well as assisting policy-makers in designing optimal programs. Adaptation of a guideline to suit the context in which it is intended to be applied can be a key step in the implementation process. Without taking the local context into account, certain interventions recommended in evidence-based guidelines may be infeasible under local conditions. Guideline adaptation frameworks provide a systematic way of approaching adaptation, and their use may increase transparency, methodological rigor, and the quality of the adapted guideline. This paper presents a number of adaptation frameworks that are currently available. We aim to compare the advantages and limitations of their processes, methods, and resource implications. These insights into adaptation frameworks can inform the future development of guidelines and systematic methods to optimize their adaptation.AnalysisRecent adaptation frameworks show an evolution from adapting entire existing guidelines, to adapting specific recommendations extracted from an existing guideline, to constructing evidence tables for each recommendation that needs to be adapted. This is a move towards more recommendation-focused, context-specific processes and considerations. There are still many gaps in knowledge about guideline adaptation. Most of the frameworks reviewed lack any evaluation of the adaptation process and outcomes, including user satisfaction and resources expended. The validity, usability, and health impact of guidelines developed via an adaptation process have not been studied. Lastly, adaptation frameworks have not been evaluated for use in low-income countries.ConclusionDespite the limitations in frameworks, a more systematic approach to adaptation based on a framework is valuable, as it helps to ensure that the recommendations stay true to the evidence while taking local needs into account. The utilization of frameworks in the guideline implementation process can be optimized by increasing the understanding and upfront estimation of resource and time needed, capacity building in adaptation methods, and increasing the adaptability of the source recommendation document.
| S-EPMC5975671 | biostudies-literature
Project description:BackgroundThe availability of a diagnostic test to detect subclinical leprosy cases is crucial to interrupt the transmission of M. leprae. In this study we assessed the minimum sensitivity level of such a (hypothetical) diagnostic test and the optimal testing strategy in order to effectively reduce the new case detection rate (NCDR) of leprosy.Methods and findingsWe used the individual-based model SIMCOLEP, and based it on previous quantification using COLEP data, a cohort study of leprosy cases in Bangladesh. The baseline consisted of treatment with Multidrug therapy of clinically diagnosed leprosy cases, passive case detection and household contact tracing. We examined the use of a leprosy diagnostic test for subclinical leprosy in four strategies: testing in 1) household contacts, 2) household contacts with a 3-year follow-up, 3) a population survey with coverage 50%, and 4) a population survey (100%). For each strategy, we varied the test sensitivity between 50% and 100%. All analyses were conducted for a high, medium, and low (i.e. 25, 5 and 1 per 100,000) endemic setting over a period of 50 years. In all strategies, the use of a diagnostic test further reduces the NCDR of leprosy compared to the no test strategy. A substantial reduction could already be achieved at a test sensitivity as low as 50%. In a high endemic setting, a NCDR of 10 per 100,000 could be reached within 8-10 years in household contact testing, and 2-6 years in a population testing. Testing in a population survey could also yield the highest number of prevented new cases, but requires a large number needed to test and treat. In contrast, household contact testing has a smaller impact on the NCDR but requires a substantially lower number needed to test and treat.ConclusionsA diagnostic test for subclinical leprosy with a sensitivity of at least 50% could substantially reduce M. leprae transmission. To effectively reduce NCDR in the short run, a population survey is preferred over household contact tracing. However, this is only favorable in high endemic settings.
| S-EPMC5991769 | biostudies-literature
Project description:The unprecedented global pandemic known as SARS-CoV-2 has exercised to its limits nearly all aspects of modern viral diagnostics. In doing so, it has illuminated both the advantages and limitations of current technologies. Tremendous effort has been put forth to expand our capacity to diagnose this deadly virus. In this work, we put forth key observations in the functionality of current methods for SARS-CoV-2 diagnostic testing. These methods include nucleic acid amplification-, CRISPR-, sequencing-, antigen-, and antibody-based detection methods. Additionally, we include analysis of equally critical aspects of COVID-19 diagnostics, including sample collection and preparation, testing models, and commercial response. We emphasize the integrated nature of assays, wherein issues in sample collection and preparation could impact the overall performance in a clinical setting.
| S-EPMC7568947 | biostudies-literature