Kuhnberntsen6781

Inherited retinal dystrophies are a group of monogenic disorders that, as a whole, contribute significantly to the burden of ocular disease in both pediatric and adult patients. In their syndromic forms, retinal dystrophies can be observed in association with intellectual disability, frequently alongside other systemic manifestations. There are now over 80 genes implicated in syndromic retinal dystrophies with intellectual disability. Identifying and accurately characterizing these disorders allows the clinician to narrow the differential diagnosis, evaluate for relevant associated features, arrive at a timely and accurate diagnosis, and address both sight-threatening ocular manifestations and morbidity-causing systemic manifestations. The co-occurrence of retinal dystrophy and intellectual disability in an individual can be challenging to investigate, diagnose, and counsel given the considerable phenotypic and genotypic heterogeneity that exists within this broad group of disorders. We performed a review of the current literature and propose an algorithm to facilitate the evaluation, and clinical and mechanistic classification, of these individuals.The hallmark pathologies of the Alzheimer's disease (AD) brain are amyloid beta (Aβ)-containing senile plaques and neurofibrillary tangles formed from the microtubule (MT)-binding tau protein. Tau becomes hyperphosphorylated and disengages from MTs in AD, with evidence of resulting MT structure/function defects. Brain-penetrant MT-stabilizing compounds can normalize MTs and axonal transport in mouse models with tau pathology, thereby reducing neuron loss and decreasing tau pathology. MT dysfunction is also observed in dystrophic axons adjacent to Aβ plaques, resulting in accumulation of amyloid precursor protein (APP) and BACE1 with the potential for enhanced localized Aβ generation. We have examined whether the brain-penetrant MT-stabilizing compound CNDR-51657 might decrease plaque-associated axonal dystrophy and Aβ release in 5XFAD mice that develop an abundance of Aβ plaques. Administration of CNDR-51657 to 1.5-month-old male and female 5XFAD mice for 4 or 7 weeks led to decreased soluble brain Aβ that coincided with reduced APP and BACE1 levels, resulting in decreased formation of insoluble Aβ deposits. These data suggest a vicious cycle whereby initial Aβ plaque formation causes MT disruption in nearby axons, resulting in the local accumulation of APP and BACE1 that facilitates additional Aβ generation and plaque deposition. The ability of a MT-stabilizing compound to attenuate this cycle, and also reduce deficits resulting from reduced tau binding to MTs, suggests that molecules of this type hold promise as potential AD therapeutics.The current study examined a conceptual model of the association between potentially morally injurious events (PMIEs) and depression symptoms. It was hypothesized that interpersonal needs (i.e., perceived burdensomeness and thwarted belongingness) would independently mediate the relationship between PMIEs and depression symptoms, while emotion dysregulation would moderate the associations. Individuals who experienced a traumatic event and were residing in the United States (N = 147) completed a cross-sectional questionnaire containing measures of PMIEs, interpersonal needs, emotion dysregulation and depression symptoms. Results indicated that the indirect effect through perceived burdensomeness was significant at high levels of emotion dysregulation, whereas the indirect effect through thwarted belongingness was non-significant. Additionally, emotion dysregulation moderated each pathway, with the exception of the direct effects from PMIEs to depression symptoms. The proposed model may be informative for researchers and clinicians interested in the association between PMIEs and depression symptoms. The results may encourage the use of emotion regulation strategies to assist patients suffering from depression symptoms, especially when exposure to a PMIE has occurred.

The number of patients infected with Aspergillus rose dramatically in recent years. However, studies on the clinical spectrum and antifungal susceptibilities of non-classical (non-fumigatus, non-flavus, non-niger and non-terreus) pathogenic Aspergillus species are very limited.

We examined the clinical spectrum and antifungal susceptibilities of 34 non-duplicated, non-classical Aspergillus isolates collected from Hong Kong, Shenzhen and Shanghai.

The Aspergillus isolates were identified by internal transcribed spacer, partial BenA and partial CaM sequencing and phylogenetic analyses. Susceptibility testing against eight antifungals was performed following the European Committee for Antimicrobial Susceptibility Testing's methodology.

The 34 Aspergillus isolates were identified as 14 different rare/cryptic species of four sections (Flavi [n=8], Nidulantes [n=8], Nigri [n=17] and Restricti [n=1]). Except for one patient whose clinical history could not be retrieved, 72.7% of the remaining patients had unnt management.This review article addresses the largely unanticipated convergence of two landmark discoveries. The first is the discovery of interferons, critical signaling molecules for all aspects of both innate and adaptive immunity, discovered originally by Isaacs and Lindenmann at the National Institute for Medical Research, London, in 1957 (Proceedings of the Royal Society of London. Series B Biological Sciences, 1957, 147, 258). The second, formerly unrelated discovery, by Leonard Hayflick and Paul Moorhead (Wistar Institute, Philadelphia) is that cultured cells undergo an irreversible but viable growth arrest, termed senescence, after a finite and predictable number of cell divisions (Experimental Cell Research, 1961, 25, 585). This phenomenon was suspected to relate to organismal aging, which was confirmed subsequently (Nature, 2011, 479, 232). Cell senescence has broad-ranging implications for normal homeostasis, including immunity, and for diverse disease states, including cancer progression and response to therapy (Nature Medicine, 2015, 21, 1424; Cell, 2019, 179, 813; Cell, 2017, 169, 1000; Trends in Cell Biology, 2018, 28, 436; Journal of Cell Biology, 2018, 217, 65). Here, we critically address the bidirectional interplay between interferons (focusing on type I) and cell senescence, with important implications for health and healthspan.With the development of hydrogen-energy economy, it is urgent for researchers to explore high effective non-noble metal electrocatalysts for oxygen evolution reaction (OER). Nickel-based selenides have good conductivity and easy to regulate, which make them to be a promising OER electrocatalysts. Hence, many researchers engineering the structure of Nickel-based selenides to further improve the OER performance. In this paper, NixFe1-x Se2 porous-nano-microspheres with different ratio were synthesized. Results confirm that Fe not only affects the number of active sites in NiSe2 , but also affects the intrinsic activity by forming lattice defects. Besides, introduction of Fe can change the redox ability of Ni cation and Se anion, thus, reducing the average valence state of Ni cation in NiOOH. As a result, the current density of OER is improved remarkably. When the current density reaches 10 mA cm-2 , the overpotential is only 285 mV.

Endovascular therapy (EVT) has become standard care for acute ischaemic stroke caused by large-vessel occlusion in the anterior circulation. However, access to this treatment in Europe remains poor. The lack of operators is a contributing factor and there is on-going discussion as to whether other specialists, including neurologists, could contribute to the EVT workforce. The question remains whether the next generation of neurologists want to become 'interventional neurologists'. The aim of this study was to address this question.

We conducted a short survey within the National Representatives Network (a division of the Resident and Research Fellow Section, European Academy of Neurology) in order to determine the interest of future neurologists in performing EVT.

A total of 1218 responses from 27 European countries were received, with some variation in the number of respondents and results among individual countries. In total, 568 neurology trainees (47%) stated that they would want to be an 'interventional neurologist'.

Our findings suggest that neurologists could make a significant contribution to the workforce performing EVT and have important implications for the development and uptake of training programmes in Europe.

Our findings suggest that neurologists could make a significant contribution to the workforce performing EVT and have important implications for the development and uptake of training programmes in Europe.Our objective was to determine the molecular mechanisms by which lncRNA HOXA-AS3 regulates the biological behaviour of glioblastoma multiforme (GBM). We used an lncRNA microarray assay to identify GBM-related lncRNA expression profiles. Qrt-PCR was used to survey the levels of expression of long non-coding RNA (lncRNA) HOXA-AS3 and the target gene. Dual-luciferase reporter assays were used to investigate the interaction of lncRNA HOXA-AS3, the target gene and miRNA. Western blot analysis was used to examine the expression of USP3 and epithelial-mesenchymal transition (EMT) genes. The MTT assay, transwell assay and wound healing assay were used to analyse the effects of lncRNA HOXA-AS3 on GBM cell viability, mobility and invasiveness, respectively. Our results showed that lncRNA HOXA-AS3 was significantly up-regulated in GBM cells and could promote GBM cell proliferation, invasion and migration in vitro and in vivo. HOXA-AS was found to be associated with poor survival prognosis in glioma patients. The dual-luciferase reporter assay also revealed that lncRNA HOXA-AS3 acts as a mir-455-5p sponge by up-regulating USP3 expression to promote GBM progression. Western blot analysis showed that lncRNA HOXA-AS3 could up-regulate EMT-related gene expression in GBM. Experiments showed mir-455-5p could rescue the effect of lncRNA HOXA-AS3 on cell proliferation and invasion. The newly identified HOXA-AS3/mir-455-5p/USP3 pathway offers important clues to understanding the key mechanisms underlying the action of lncRNA HOXA-AS3 in glioblastoma.Autism spectrum disorder (ASD) is characterized by social interaction and communication impairments, as well as restrictive/repetitive patterns of behavior, interests or activities, which can coexist with intellectual disability and altered sensory processing. To study the mechanisms underlying these core features of ASD, preclinical research has developed animal models with manipulations in ASD-linked genes, such as CNTNAP2. In order to fully interpret the findings from mechanistic studies, the extent to which these models display behaviors consistent with ASD must be determined. Toward that goal, we conducted an investigation of the consequences of a functional loss of Cntnap2 on ASD-related behaviors by comparing the performance of rats with a homozygous or heterozygous knockout of Cntnap2 to their wildtype littermates across a comprehensive test battery. Cntnap2-/- rats showed deficits in sociability and social novelty, and they displayed repetitive circling and hyperlocomotion. Moreover, Cntnap2-/- rats demonstrated exaggerated acoustic startle responses, increased avoidance to sounds of moderate intensity, and a lack of rapid audiovisual temporal recalibration; indicating changes in sensory processing at both the pre-attentive and perceptual levels.