Analysis on the impact of additives on space charge behavior of thermally aged XLPE plaques

This article investigates the space charge properties of XLPE-based materials characterized by different concentration and types of additives and fillers inside the polymeric compound. Materials were aged under three different temperatures (87 °C, 110 °C and 130 °C) for 24, 18 and 12 months, respectively. Space charge profiles of both unaged and aged materials were obtained through the Pulsed Electro Acoustic (PEA) method. Additives and fillers are proven to significantly impact the space charge behavior of the insulating material both in the unaged and aged states. The impact of antioxidants, together with their kinetics under thermal aging conditions, is analyzed and claims an effective containment of the degradation kinetics, keeping the accumulated space charge to low values

The anatomo-clinical picture of the pathological embodiment over someone else's body part after stroke

Recently, a monothematic delusion of body ownership due to brain damage (i.e., the embodiment of someone else's body part within the patient's sensorimotor system) has been extensively investigated. Here we aimed at defining in-depth the clinical features and the neural correlates of the delusion. Ninety-six stroke patients in a sub-acute or chronic phase of the illness were assessed with a full ad-hoc protocol to evaluate the embodiment of an alien arm under different conditions. A sub-group of seventy-five hemiplegic patients was also evaluated for the embodiment of the movements of the alien arm. Fifty-five patients were studied to identify the neural bases of the delusion by means of voxel-based lesion-symptom mapping approach. Our results show that, in forty percent of the whole sample, simply viewing the alien arm triggered the delusion, but only if it was a real human arm and that was seen from a 1st person perspective in an anatomically-correct position. In the hemiplegic sub-group, the presence of the embodiment of the alien arm was always accompanied by the embodiment of its passive and active movements. Furthermore, the delusion was significantly associated to primary proprioceptive deficits and to damages of the corona radiata and the superior longitudinal fasciculus. To conclude, we show that the pathological embodiment of an alien arm is well-characterized by recurrent and specific features and might be explained as a disconnection deficit, mainly involving white matter tracts. The proposed exhaustive protocol can be successfully employed to assess stroke-induced disorders of body awareness, unveiling even their more undetectable or covert clinical forms

CT-derived pulmonary vascular metrics and clinical outcome in COVID-19 patients

To assess pulmonary vascular metrics on chest CT of COVID-19 patients, and their correlation with pneumonia extent (PnE) and outcome, we analyzed COVID-19 patients with an available previous chest CT, excluding those performed for cardiovascular disease. From February 21 to March 21, 2020, of 672 suspected COVID-19 patients from two centers who underwent CT, 45 RT-PCR-positives (28 males, median age 75, IQR 66-81 years) with previous CTs performed a median 36 months before (IQR 12-72 months) were included. We assessed PnE, pulmonary artery (PA) diameter, ascending aorta (Ao) diameter, and PA/Ao ratio. Most common presentations were fever and dyspnea (15/45) and fever alone (13/45). Outcome was available for 41/45 patients, 15/41 dead and 26/41 discharged. Ground-glass opacities (GGOs) alone were found in 29/45 patients, GGOs with consolidations in 15/45, consolidations alone in 1/45. All but one patient had bilateral pneumonia, 9/45 minimal, 22/45 mild, 9/45 moderate, and 5/45 severe PnE. PA diameter (median 31 mm, IQR 28-33 mm) was larger than before (26 mm, IQR 25-29 mm) (P<0.001), PA/Ao ratio (median 0.83, IQR 0.76-0.92) was higher than before (0.76, IQR 0.72-0.82) (P<0.001). Patients with adverse outcome (death) had higher PA diameter (P=0.001), compared to discharged ones. Only weak correlations were found between Delta PA or Delta PA/Ao and PnE (rho <= 0.453, P <= 0.032), with 4/45 cases with moderate-severe PnE and minimal increase in PA metrics. In conclusion, enlarged PA diameter was associated to death in COVID-19 patients, a finding deserving further investigation as a potential driver of therapy decision-making

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

Success factors of global goal-setting for sustainable development:Learning from the millennium development goals

The Millennium Development Goals (MDGs) were an important precursor to the Sustainable Development Goals (SDGs). Hence, identifying the conditions that made the MDGs successful enhances our understanding of global goal-setting and informs the global endeavour to achieve the SDGs. Drawing on a comprehensive review of 316 articles published between 2009 and 2018, we identify six factors that have enabled or hindered MDG implementation. Our analysis stresses the importance of path dependencies and shows that the MDGs catalysed changes only for those countries with sufficient resource availability, administrative capacity and economic development, as well as adequate support from external donors. National ownership and NGO pressure bolstered efforts to implement the MDGs. These findings suggest that globally agreed goals do not easily trickle down from the global to the national level. Thus, this article adopts a forward-looking perspective and draws key lessons for the current implementation of the SDGs in developing countries

EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias

Background and purpose:  These EFNS guidelines on the molecular diagnosis of neurogenetic disorders are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics in diagnosing neurogenetic disorders.Methods:  Literature searches were performed before expert members of the task force wrote proposals, which were discussed in detail until final consensus had been reached among all task force members.Results and conclusion:  This paper provides updated guidelines for molecular diagnosis of two particularly complex groups of disorders, the ataxias and spastic paraplegias. Possibilities and limitations of molecular genetic diagnosis of these disorders are evaluated and recommendations are provided

Gastrointestinal bleeding in patients with sars-cov-2 infection managed by interventional radiology

Background: This study was conducted to evaluate the technical and clinical success of trans-arterial embolization (TAE) as a treatment of gastrointestinal bleeding (GIB) in Coronavirus Disease 2019 (COVID-19) patients and to describe its safety; moreover, we describe the characteristics of these patients. Methods: Thirty-four COVID-19 hospitalized patients presented with GIB. Risk factors, drugs administered for COVID-19 infection, and clinical and biological parameters were evaluated. Furthermore, intraprocedural data and outcomes of embolization were analyzed. Results: GIB was more frequent in male. Overweight, hypertension, diabetes, previous cardiac disease, and anticoagulation preadmission (48.5%) were frequently found in our population. Previous or actual COVID Acute respiratory distress syndrome (ARDS) and a high level of D-dimer were encountered in most cases. Upper GIB was more frequent than lower GIB. Technical and clinical success rates of embolization were 88.2% and 94.1%, respectively. The complication rate was 5.9%. Conclusions: Our study highlights the most frequent characteristics of COVID-19 patients with GIB. Embolization is feasible, effective, and safe

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial disease.

OBJECTIVE: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations. METHODS: RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic and molecular evaluation of the newly identified and previously reported patients harboring RNASEH1 mutations was subsequently undertaken. RESULTS: Pathogenic c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74 probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic analysis was undertaken in 50 additional Indian probands with variable clinical presentations associated with multiple mtDNA deletions, but no further RNASEH1 mutations were confirmed. RNASEH1-related mitochondrial disease was characterized by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial disease, haplotype analysis suggested an independent origin, rather than a founder event, for the variant in our families. CONCLUSIONS: In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analysis should also be considered in all patients with POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further investigation

What is memory? The present state of the engram

The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today