A taxonomy of cognitive phenotypes in Multiple Sclerosis: a 1-year longitudinal study

As meaningful measure of cognitive impairment (CI), cognitive phenotypes provide an avenue for symptom management and individualized rehabilitation. Since CI is highly variable in severity and progression, monitoring cognitive phenotypes over time may be useful to identify trajectory of cognitive decline in Multiple Sclerosis (MS). Based on cognitive and mood information from patient-reported outcomes (PROs) and clinician-assessed outcomes (CAOs), four cognitive subgroups of people with MS (PwMS) were identified: phenotype 1 (44.5%) showed a preserved cognitive profile; phenotype 2 (22.8%) had a mild-cognitive impairment profile with attention difficulties; phenotype 3 (24.3%) included people with marked difficulties in visuo-executive, attention, language, memory and information processing speed; lastly, phenotype 4 (8.4%) grouped individuals with a multi-domain impairment profile (visuo-executive, attention, language, memory, orientation, information processing speed and mood disorders). Although some fluctuations occurred considering the rate of impairment, cognitive phenotypes did not substantially vary at follow up in terms of type and number of impairments, suggesting that 1 year is a relatively brief temporal window to observe considerable changes. Our results corroborate that investigating cognitive phenotypes and their stability over time would provide valuable information regarding CI and, in addition, increase clinical importance of PROs and CAOs and their uptake in decision-making and individualized treatment planning for PwMS

Job Retention by People With Disabilities: A Qualitative Study of the Perspectives of People With Multiple Sclerosis

Background: Multiple sclerosis (MS), because of its early age at onset, greatly impacts the working lives of those affected by it in ways linked to different factors, both professional and personal. It has been observed that only a small percentage (20-40%) of workers with MS retain their jobs after the diagnosis. When identifying factors determining job retention or loss in this setting, it is essential to consider the direct perspectives of people with MS (PwMS). Methods: A qualitative study, based on the conduction of two focus groups, was conducted to explore the personal experiences of PwMS who work. Results: The results show that there are numerous factors, both positive and negative, that can influence these people's ability to retain their jobs. The climate established in the workplace and the relationship between workers with MS and their colleagues were fundamentally important aspects, as was knowledge of the disease at the level of public opinion. Conclusions: Managing work is a complex undertaking for people with a disabling condition like MS. There needs to be greater awareness of the employment rights of PwMS. Improving these knowledge-based aspects could undoubtedly improve the quality of the working lives of PwM

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Parental Expressed Emotion During Two Forms of Family-Based Treatment for Adolescent Anorexia Nervosa.

High parental expressed emotion (EE), reflected by criticism or emotional over-involvement, has been related to poorer outcome in family-based treatment (FBT) for adolescent anorexia nervosa. This study assessed EE in 89 mothers and 64 fathers at baseline and end of treatment in a randomised trial comparing conjoint FBT to parent-focused FBT (PFT). Compared with conjoint FBT, PFT was associated with a decrease in maternal criticism, regardless of adolescent remission. Furthermore, an increase in maternal criticism was more likely to be observed in conjoint FBT (80%) than PFT (20%, p = 0.001). Adolescents of mothers who demonstrated an increase in EE, or remained high in EE, were less likely to remit compared with adolescents for whom EE decreased or remained low (33% and 0% vs. 43% and 50%, p = 0.03). There were no significant effects for paternal EE. The results highlight the importance of considering EE when implementing FBT for adolescents with anorexia nervosa. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association

Parental Expressed Emotion During Two Forms of Family-Based Treatment for Adolescent Anorexia Nervosa.

High parental expressed emotion (EE), reflected by criticism or emotional over-involvement, has been related to poorer outcome in family-based treatment (FBT) for adolescent anorexia nervosa. This study assessed EE in 89 mothers and 64 fathers at baseline and end of treatment in a randomised trial comparing conjoint FBT to parent-focused FBT (PFT). Compared with conjoint FBT, PFT was associated with a decrease in maternal criticism, regardless of adolescent remission. Furthermore, an increase in maternal criticism was more likely to be observed in conjoint FBT (80%) than PFT (20%, p = 0.001). Adolescents of mothers who demonstrated an increase in EE, or remained high in EE, were less likely to remit compared with adolescents for whom EE decreased or remained low (33% and 0% vs. 43% and 50%, p = 0.03). There were no significant effects for paternal EE. The results highlight the importance of considering EE when implementing FBT for adolescents with anorexia nervosa. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association