Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study

Background: Patients with paediatric-onset multiple sclerosis (POMS) could be at an increased risk for cognitive impairment (CI), given the potential harmful effects of disease activity in neurodevelopment. However, there is scarce information on their long-term cognitive outcomes. Objective: To compare the prevalence and profile of CI between adults with a history of POMS and those with classic, adult-onset multiple sclerosis (AOMS). Methods: Cognitive performance was assessed through the Brief Repeatable Battery (BRB) and the Stroop Test in consecutive patients referred to six Italian MS centres. CI was defined as impairment in ⩾2 cognitive domains. Results: In all, 119 patients with POMS and 712 with AOMS were included in this analysis. The prevalence of CI was 48.0% in AOMS, 44.5% in POMS; with similar neuropsychological profile between the two groups. However, when adjusting for current age, we found a significantly increased risk for CI (odds ratio (OR) = 1.71; p = 0.02) and for impairment in information processing speed (OR = 1.86; p < 0.01) in patients with POMS. A higher Expanded Disability Status Scale (EDSS) was also identified in POMS (p = 0.03) compared with AOMS patients.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This study was in part financed through an FISM (Italian Federation of Multiple Sclerosis) research grant

Correction to: Aging with multiple sclerosis: prevalence and profile of cognitive impairment

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Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping

Telomere integrity in budding yeast depends on the CST (Cdc13-Stn1-Ten1) and shelterin-like (Rap1-Rif1-Rif2) complexes, which are thought to act independently from each other. Here we show that a specific functional interaction indeed exists among components of the two complexes. In particular, unlike RIF2 deletion, the lack of Rif1 is lethal for stn1ΔC cells and causes a dramatic reduction in viability of cdc13-1 and cdc13-5 mutants. This synthetic interaction between Rif1 and the CST complex occurs independently of rif1Δ-induced alterations in telomere length. Both cdc13-1 rif1Δ and cdc13-5 rif1Δ cells display very high amounts of telomeric single-stranded DNA and DNA damage checkpoint activation, indicating that severe defects in telomere integrity cause their loss of viability. In agreement with this hypothesis, both DNA damage checkpoint activation and lethality in cdc13 rif1Δ cells are partially counteracted by the lack of the Exo1 nuclease, which is involved in telomeric single-stranded DNA generation. The functional interaction between Rif1 and the CST complex is specific, because RIF1 deletion does not enhance checkpoint activation in case of CST-independent telomere capping deficiencies, such as those caused by the absence of Yku or telomerase. Thus, these data highlight a novel role for Rif1 in assisting the essential telomere protection function of the CST complex

Experimental oncogenicity by human papovaviruses and possible correlations with human tumors.

none3---noneBarbanti-Brodano G.; Corallini A.; Grossi M.P.BARBANTI BRODANO, Giuseppe; Corallini, Alfredo; Grossi, Maria Pi

Tandem integration of complete viral genomes can occur in nonpermissive hamster cells transformed by linear BKV DNA with cohesive ends.

none6---Chenciner N., Centre de Biochimie Facultè des Sciences, Parc Valrose, 06034 Nice, FrancenoneGrossi M.P.; Corallini A.; Meneguzzi G.; Chenciner N.; Barbanti-Brodano G.; Milanesi G.Grossi, Maria Pia; Corallini, Alfredo; Meneguzzi, G.; Chenciner, N.; BARBANTI BRODANO, Giuseppe; Milanesi, G

Analysis of BK virus-transformed cells and BK virus-induced tumors by DNA-DNA reassociation kinetics

none6BK virus (BKV)-transformed cells and BKV-induced tumors as well as in vitro derived tumor cell lines were all found to contain BKV DNA sequences when analysed by DNA-DNA reassociation kinetics. In transformed cells the number of viral genome equivalents per diploid cell genome (VG/CG) decreased with increasing generations. Likewise, single cell clones had a lower VG/CG than parental transformed cells. BKV-induced tumors had a high VG/CG. Tumor cells cultivated in vitro and their clones had a lower VG/CG than BKV-induced tumors from which they were derived, suggesting a multiclonal origin of tumors. Hamster tumors induced by subcutaneous inoculation of BKV-transformed cells or tumor cell lines had a higher VG/CG than cells producing them. Variation in VG/CG is discussed in terms of cell selection depending on different in vitro or in vivo conditions of cell growth. In some cases, however, the decrease in VG/CG most likely depends on loss of free viral sequences from transformed cells or tumors. © 1981 Springer-Verlag.noneGrossi M.P.; Corallini A.; Poli F.; Valieri A.; Milanesi G.; Barbanti-Brodano G.Grossi, Maria Pia; Corallini, Alfredo; Poli, Ferruccio; Valieri, A.; Milanesi, G.; BARBANTI BRODANO, Giusepp

The arrangement of integrated viral DNA is different in BK virus-transformed mouse and hamster cells

none6---noneMeneguzzi G.; Chenciner N.; Corallini A.; Grossi M.P.; Barbanti-Brodano G.; Milanesi G.Meneguzzi, G.; Chenciner, N.; Corallini, Alfredo; Grossi, Maria Pia; BARBANTI BRODANO, Giuseppe; Milanesi, G

Integrated and free viral DNA in hamster tumors induced by BK virus.

none7---Chenciner, Centre de Biochimie, Facultè des Sciences, Parc Valrose, 06034 Nice, FrancenoneChenciner N.; Meneguzzi G.; Corallini A.; Grossi M.P.; Grassi P.; Barbanti-Brodano G.; Milanesi G.Chenciner, N.; Meneguzzi, G.; Corallini, Alfredo; Grossi, Maria Pia; Grassi, P.; BARBANTI BRODANO, Giuseppe; Milanesi, G