Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

提高中国泌尿系结石研究水平的几点建议

近年来我国在泌尿系结石的基础研究和临床应用方面不断取得突破性进展,令人瞩目,但仍缺乏高质量、系统性的研究体系和高影响力的研究成果。在提高我国泌尿系结石研究水平方面,我认为应重视开展高质量临床医学研究,改变观念和评价体系,打破专业屏障,促进多学科合作,加强泌尿系结石的转化医学研究,加强产学研合作以促进国产医疗设备的研发。多管齐下,以进一步提高中国泌尿系结石的研究水平。     

Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

BackgroundNeoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.Patients and MethodsDNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral heterogeneity. Response to nCRT was pathologically scored after surgical resection.ResultsBiopsy samples from 21 patient tumors were analyzed. Eight patients had disease noted to have complete response, 2 moderate, 4 minimal, and 7 poor. Higher MATH scores correlated with poorer response to treatment, demonstrating significantly increased tumor heterogeneity compared to complete response (P = .039).ConclusionThe application of MATH scores as a measure of tumor heterogeneity may provide a useful biomarker for treatment response in locally advanced rectal cancer.     

Overview of prospects for inflammation pathways in autism spectrum disorders

Autism spectrum disorders (ASD) represent a heterogeneous group of neurodevelopmental disorders which are both severe and frequent. Understanding its pathophysiology could lead to identifying promising new markers and treatments. For years, a growing number of studies have pointed to an important involvement of the immuno-inflammatory system in ASD. Extensive reviews have already addressed this topic. Yet, this field of investigations is not well known to practitioners even those working with ASD patients. Our main objective is to provide an introduction to these new insights through a mini review of the literature. A first field of antenatal studies connects fetal features and maternal infections to ASD by means of the participation of maternal immune activation (MIA) associated with the production of a particular pro inflammatory cytokinic profile with IL-1, IL-6 and TNF and IL-17. Maternal autoantibodies and other immune-related disorders can also lead to impairment of fetal neurodevelopment. Other postnatal studies have shown the correlation between ASD and autoantibodies and between ASD and inflammatory environment through impaired interleukin levels (IL-6 being the most extensively investigated). Disruption of intestinal microbiota appears to be a possible pathogenic mechanism of ASD. The growing paths opened recently between immunology and psychiatry appear to be promising in the understanding of ASD. It could eventually participate in the development of diagnostic markers and help the emergence of new personalized therapeutics suitable for these patients.     

Filling the gaps on stroke research: Focus on inflammation and immunity

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19.We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.     

Magnetic Field Interactions of Orthodontic Wires during Magnetic Resonance Imaging (MRI) at 1.5 Tesla

AbstractBackground: Orthodontic appliances pose a potential risk during magnetic resonance imaging (MRI) due to forces on metallic objects within the static magnetic field of MRI systems. The aim of the present investigation was to measure forces on orthodontic wires caused by the static magnetic field of a 1.5-Tesla MRI system, and to assess the safety hazards associated with these forces.Materials and Methods: Thirty-two different orthodontic wires (21 arch wires, eight ligature wires and three retainer wires) were investigated in a 1.5-Tesla MRI system (Magnetom Symphony, Siemens Medical Solutions, Erlangen, Germany). The translational forces were measured using the deflection angle test (ASTM F2052-02); rotational forces were assessed on a 5-point qualitative scale.Results and Conclusion: All retainer wires and the steel arch wires (the Noninium^® arch wire being the exception) were subjected to considerable rotational and translational forces within the MRI system’s magnetic field. Translational forces were from 9.1- to 27.6-times as high as gravitational forces on these objects. Steel ligature wires and arch wires made of cobalt chromium, titanium molybdenum, nickel-titanium, and brass alloys showed no or negligible forces within the magnetic field. The translational and rotational forces within the MRI magnetic field should pose no risk to carefully-ligated arch wires. Steel retainer wire bonds should be checked to ensure secure attachment prior to an MRI investigation.* both authors share first authorship