Dr. Albert P. Marshall, Oral History Interview, 1998

Dr. Albert P. Marshall served Eastern Michigan University from 1969 until 1980, during which time he taught library science, served as Library Director and Dean of Academic Services. This interview serves as a comprehensive biography of Marshall, from childhood through his time as Dean of Academic Services at Eastern Michigan University. Notable are Marshall’s experiences as librarian for the United States Coast Guard before arriving at EMU, and his concern for the welfare of black students at Eastern. This interview was conducted for the purpose of gathering primary research for Laurence Smith’s book, Eastern Michigan University: A Sesquicentennial Portrait (1999).https://commons.emich.edu/oral_histories/1006/thumbnail.jp

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non -responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy

Neonatal Seizures: An Overview of Genetic Causes and Treatment Options

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions

COVID-19 Emergency and Post-Emergency in Italian Cancer Patients: How Can Patients Be Assisted?

Italy and worldwide are experiencing an outbreak of a new coronavirus-related disease, named COVID-19, declared by the WHO COVID-19 a pandemic. The fragility of cancer patients is well-known, with many cases affecting aged patients or those with several comorbidities that frequently result in a loss of independency and functionality. Therefore, cancer patients have been greatly affected by this health emergency and, due to their vulnerability to COVID-19, oncologic patient visits have been often delayed or canceled leading to possible under-treatment. Different solutions can be adopted for reducing travels to cancer screening centers and the overall impact of cancer screening visits. As a consequence, it has been recommended that, when possible, the follow-up visits for cancer patients treated with oral anticancer drugs could be performed telematically. Furthermore, many patients refuse hospital visits, even if necessary, because of fear of contagion. Moreover, in some regions in Italy even the very first non-urgent visits have been postponed with the consequent delay in diagnosis, which may negatively affect disease prognosis. For these reasons, new approaches are needed such as the telemedicine tool. Throughout organized and appropriate tools, it would be possible to manage patients' visits and treatments, to avoid the dangerous extension of waiting lists when the standard activities will resume. In this context, a number of hospital visits can be substituted with visits at small local health centers, and general practitioners'office, taking in turn, advantage of well-defined telemedicine path which will be developed in the post-emergency phase

Identification of a Novel Missense Mutation of <i>POLR3A</i> Gene in a Cohort of Sicilian Patients with Leukodystrophy

Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD

The natural phosphoinositide derivative glycerophosphoinositol inhibits the lipopolysaccharide-induced inflammatory and thrombotic responses

Inflammatory responses are elicited through lipid products of phospholipase A(2) activity that acts on the membrane phospholipids, including the phosphoinositides, to form the proinflammatory arachidonic acid and, in parallel, the glycerophosphoinositols. Here, we investigate the role of the glycerophosphoinositol in the inflammatory response. We show that it is part of a negative feedback loop that limits proinflammatory and prothrombotic responses in human monocytes stimulated with lipopolysaccharide. This inhibition is exerted both on the signaling cascade initiated by the lipopolysaccharide with the glycerophosphoinositol-dependent decrease in IB kinase /, p38, JNK, and Erk1/2 kinase phosphorylation and at the nuclear level with decreased NF-B translocation and binding to inflammatory gene promoters. In a model of endotoxemia in the mouse, treatment with glycerophosphoinositol reduced TNF- synthesis, which supports the concept that glycerophosphoinositol inhibits the de novo synthesis of proinflammatory and prothrombotic compounds and might thus have a role as an endogenous mediator in the resolution of inflammation. As indicated, this effect of glycerophosphoinositol can also be exploited in the treatment of manifestations of severe inflammation by exogenous administration of the compound

Elaborazione della matrice di valutazione della trasformabilità dei drosscape. Indicatori, moltiplicatori e interpretazione dei risultati

Attribuzione del grado di trasformabilità dei drosscape (vuoti urbani abbandonati nel territorio della Coda della Cometa) attraverso l'elaborazione di una matrice e della definizione dei criteri di valutazione. Analisi dei risultati dei valori applicati alla matrice e utilizzo di nuovi moltiplicatori. Elaborazione delle mappe delle potenzialità di trasformazione dei drosscape

Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders