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Heterosigma akashiwoshows remarkable ultrastructural changes during the recovery from a late stationary phase (“aged” culture) induced by nutrient depletion.H. akashiwocells showed different morphological types in “aged” cultures, with an increase in irregular cells and cell fragments. The irregular cells mostly corresponded to an amoeboid shape of the cell. Many of these cells showed chloroplasts with a homogeneous matrix of medium electron density lacking most thylakoids and condensed nucleus, probably as a result of cyst/resting cells germination. In other cells, we observed nuclear blebbing without chromatin condensation and changes in mitochondrion ultrastructure. Some vegetative cells in active phase (“young” culture) were connected to each other, apparently phagocytizing cytoplasmic fragments and intact chloroplasts in the medium. An explanation for the phenomenon may reside in the need of acquiring organic material after nutrient reduction for a faster recovery. On the basis of our observations, we conclude that some ultrastructural features, normally used to distinguish between different species and strains of Raphidophyceae, may be related to different physiological states and should be used with caution for systematic purposes. [ABSTRACT FROM PUBLISHER]

The article discusses a study which was aimed to test a home-based computerized program for retraining attention dysfunction in multiple sclerosis (MS). The study recruited outpatients consecutively referred to the MS Centers of the Universities of Florence and Bari. In its training program, the study detected some improvements exclusively on tasks of sustained attention.

Background: Multiple sclerosis (MS) is a chronic inflammatory disorder affecting the brain and spinal cord, characterized by immune-mediated myelin damage. Early intervention and detection programs have emerged as promising strategies to improve patient outcomes by identifying and treating MS in its earliest stages., Objective: This systematic literature review aims to provide an overview of the preferences, attitudes, and opinions of both patients and healthcare professionals regarding early intervention or early detection programs for MS., Methods: A comprehensive search strategy was employed in March 2023 across multiple databases (MEDLINE, Scopus, PsyInfo, PubMed), from 1990 to 2023. A total of 38 articles were selected for analysis based on predefined inclusion and exclusion criteria., Results: The majority of articles were published in recent years and represented different methods from case reports to randomized controlled trials, with fewer systematic literature reviews. Data collection approaches included patients, healthcare workers, or mixed samples with varying age ranges and gender ratios, frequently preferring women. These samples represented different preference study methods. The included studies were primarily conducted in the USA and the UK. Thematic analysis revealed several key themes : 1) differences emerged between healthcare professionals' and patients' perspectives 2) interventions for MS outside Disease-Modifying Therapies (DMTs) 3) severe side effects 4) communication, information, and knowledge 5) psychological and emotional aspects., Conclusions: Understanding these diverse factors and subgroups within the MS population can inform more effective, personalized approaches to MS prevention and treatment., Competing Interests: Declaration of competing interest The Authors declare having no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Wastewater-based epidemiology has proved to be a suitable approach for tracking the spread of epidemic agents including SARS-CoV-2 RNA. Different protocols have been developed for quantitative detection of SARS-CoV-2 RNA from wastewater samples, but little is known on their performance. In this study we compared three protocols based on Reverse Transcription Real Time-PCR (RT-PCR) and one based on Droplet Digital PCR (ddPCR) for SARS-CoV-2 RNA detection from 35 wastewater samples. Overall, SARS-CoV-2 RNA was detected by at least one method in 85.7 % of samples, while 51.4 %, 22.8 % and 8.6 % resulted positive with two, three or all four methods, respectively. Protocols based on commercial RT-PCR assays and on Droplet Digital PCR showed an overall higher sensitivity vs. an in-house assay. The use of more than one system, targeting different genes, could be helpful to increase detection sensitivity., Competing Interests: Declaration of Competing Interest G.M.R. reports grants, consulting fees, and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from bioMérieux, MSD, Shionogi, Zambon, Menarini, Angelini; grants from Accelerate, Cepheid, Nordic Pharma, Seegene, Arrow, Symcel, DID, Hain Lifescience, Meridian, Setlance, Qvella, Qlinea, Biomedical Service, Quidel, QuantaMatrix, SD Biosensor; consulting fees from Pfizer and Qiagen; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Becton Dickinson, Cepheid and Pfizer, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is limited information on interpretation of cognitive changes over time in multiple sclerosis (MS)., Objective: This study aimed to provide normative data for the assessment of statistically meaningful change in all tests of the Minimal Assessment of Cognitive Function in MS (MACFIMS)., Methods: We applied the reliable change methodology to a healthy Italian cohort, assessed with two alternate versions of the MACFIMS 1 year apart. We calculated confidence intervals of retest score variance using the reliable change index (RCI). Moreover, multivariable linear regression models adjusted for age, sex, education, and baseline score were built to calculate the regression-based change index (RB-CI)., Results: Overall, 200 healthy individuals were enrolled. Thresholds for interpreting change in each test were calculated. In the multivariable models, baseline score was associated with retest score in all tests ( B from 0.439 to 0.760; p < 0.001). RB-CI can be calculated with data of the multivariable models., Conclusion: We provide normative data for reliable cognitive change evaluation for all the tests of the MACFIMS, which includes the Symbol Digit Modalities Test and Brief International Cognitive Assessment in MS, two widely used tools for screening and monitoring cognition in MS. Our findings can significantly improve the interpretation of cognitive changes in MS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.P. received compensation for travel grants, participation in advisory board and speaking activities from Biogen, Merck Serono, Sanofi, Teva, Roche, BMS Celgene, Janssen, and Novartis, and served on the editorial board of Frontiers in Neurology and Brain Sciences. M.P.A. served on scientific advisory boards for and has received speaker honoraria and research support from Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi Aventis, and serves on the editorial board of Multiple Sclerosis Journal and BMC Neurology. P.G., F.B., V.B., S.C., M.F., B.G., C.N., E.P., and R.G.V. declare that there is no conflict of interest.

Objectives: To investigate a ceftazidime/avibactam (CZA)-resistant Klebsiella pneumoniae (NE368), isolated from a patient exposed to CZA, expressing a novel K. pneumoniae carbapenemase (KPC)-3 variant (KPC-109)., Methods: Antimicrobial susceptibility testing was performed by reference broth microdilution. Whole-genome sequencing (WGS) analysis of NE368 was performed combining a short- and long-reads approach (Illumina and Oxford Nanopore Technologies). Functional characterization of KPC-109 was performed to investigate the impact of KPC-109 production on the β-lactam resistance phenotype of various Escherichia coli and Klebsiella pneumoniae strains, including derivatives of K. pneumoniae with OmpK35 and OmpK36 porin alterations. Horizontal transfer of the KPC-109-encoding plasmid was investigated by conjugation and transformation experiments., Results: K. pneumoniae NE368 was isolated from a patient after repeated CZA exposure, and showed resistance to CZA, fluoroquinolones, piperacillin/tazobactam, expanded-spectrum cephalosporins, amikacin, carbapenems and cefiderocol. WGS revealed the presence of a large chimeric plasmid of original structure (pKPN-NE368), encoding a novel 270-loop mutated KPC-3 variant (KPC-109; ins&#95;270&#95;KYNKDD). KPC-109 production mediated resistance/decreased susceptibility to avibactam-based combinations (with ceftazidime, cefepime and aztreonam) and cefiderocol, with a trade-off on carbapenem resistance. However, in the presence of porin alterations commonly encountered in high-risk clonal lineages of K. pneumoniae, KPC-109 was also able to confer clinical-level resistance to carbapenems. Resistance of NE368 to cefiderocol was likely contributed by KPC-109 production acting in concert with a mutated EnvZ sensor kinase. The KPC-109-encoding plasmid did not appear to be conjugative., Conclusions: These findings expand current knowledge about the diversity of emerging KPC enzyme variants with 270-loop alterations that can be encountered in the clinical setting., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Among multidrug-resistant (MDR) bacteria able to threaten human health, carbapenem-resistant Enterobacterales (CRE) have become a major public health threat globally. National and international guidelines point out the importance of active routine surveillance policies to prevent CRE transmission. Therefore, defining lines of intervention and strategies capable of containing and controlling the spread of CRE is considered determinant. CRE screening is one of the main actions to curb transmission and control outbreaks, outlining the presence and also the prevalence and types of carbapenemase enzymes circulating locally., Objective: The purpose of this study was to outline the epidemiology of CRE colonization in Italy, detecting CRE-colonized patients at admission and during hospitalization, before and during the first year of COVID-19., Materials and Methods: A total of 11,063 patients admitted to seven different hospitals (Bologna, Catania, Florence, Genoa, Naples, Palermo, and Turin) in Intensive Care Units (ICU) and other wards (non-ICU) located in the North, Center, and South of Italy were enrolled and screened for CRE carriage at admission (T0) and during the first 3 weeks of hospitalization (T1-T3). The study spanned two periods, before (September 2018-Septemeber 2019, I observational period) and during the COVID-19 pandemic (October 2019-September 2020, II observational period)., Results: Overall, the prevalence of CRE-colonized patients at admission in ICU or in other ward, ranged from 3.9 to 11.5%, while a percentage from 5.1 to 15.5% of patients acquired CRE during hospital stay. There were large differences between the I and II period of study according to the different geographical areas and enrolling centers. Overall, comparison of prevalence of CRE-positive patients showed a significant increased trend between I and II observational periods both in ICU and non-ICU wards, mostly in the Southern participating centers. KPC-producing Klebsiella pneumoniae was the most frequent CRE species-carbapenemase combination reported in this study. In particular, the presence of KPC-producing K. pneumoniae was reported in period I during hospitalization in all the CRE-positive patients enrolled in ICU in Turin (North Italy), while in period II at admission in all the CRE-positive patients enrolled in ICU in Catania and in 58.3% of non-ICU CRE-positive patients in Naples (both centers in South Italy)., Conclusion: The prevalence of CRE in Italy highly increased during the COVID-19 pandemic, mostly in the Southern hospital centers. KPC-producing K. pneumoniae was the most frequent colonizing CRE species reported. The results of our study confirmed the crucial value of active surveillance as well as the importance of multicenter studies representing diverse geographical areas even in endemic countries. Differences in CRE colonization prevalence among centers suggest the need for diversified and center-specific interventions as well as for strengthening efforts in infection prevention and control practices and policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fasciana, Antonelli, Bianco, Lombardo, Codda, Roscetto, Perez, Lipari, Arrigo, Galia, Tricoli, Calvo, Niccolai, Morecchiato, Errico, Stefani, Cavallo, Marchese, Catania, Ambretti, Rossolini, Pantosti, Palamara, Sabbatucci, Serra and Giammanco.)

Purpose/objective: Within the framework of the Salutogenic Model of Health, this study aimed to investigate sense of coherence among caregiving partners of persons with multiple sclerosis (PwMS), and its relationship with perceived social support and illness beliefs conceived as generalized resistance resources in tension management., Research Method/design: In this cross-sectional study, 398 caregiving partners of PwMS ( M age = 44.62; 34.9% women and 65.1% men) filled in questionnaires measuring sense of coherence (Sense of Coherence Scale-13), perceived social support from family, friends and significant others (Multidimensional Scale of Perceived Social Support), and illness beliefs (Revised Illness Perception Questionnaire). Hierarchical linear regression analysis was performed to assess the contribution of perceived support and illness beliefs to sense of coherence, controlling for sociodemographic and clinical variables., Results: Perceived support from family and beliefs concerning illness-related emotional representations, illness coherence, and treatment control emerged as significant predictors of participants' sense of coherence. Higher perceived support from family and stronger beliefs in illness coherence and treatment control were associated with higher sense of coherence, while more negative emotional representations were related to lower sense of coherence values., Conclusions/implications: Findings lend support to the relevance of a salutogenic approach to caregiving in multiple sclerosis. They further suggest the usefulness of interventions that can promote caregivers' sense of coherence and successful coping in life by benefitting from family support, favoring the construction of a coherent illness view, offering comprehensive information and expert guidance on treatment and rehabilitation opportunities, and promoting adaptive management of negative emotions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Cefiderocol is a catechol-substituted cephalosporin with potent in vitro activity against carbapenem-resistant (CR) Gram-negative bacteria (GNB). Cefiderocol susceptibility testing is complex because iron concentrations need to be taken into consideration. Here, we assessed the clinical performance of Bruker's UMIC® Cefiderocol and corresponding iron-depleted CAMHB to determine MIC by broth microdilution (BMD) for clinically relevant GNB., Methods: MICs of cefiderocol for 283 GN clinical isolates were determined by BMD using iron-depleted CAMHB. Frozen panels were used as a reference. The concentration range of cefiderocol was 0.03-32 mg/L. The isolates, with different degrees of susceptibility to cefiderocol, included Enterobacterales (n = 180), Pseudomonas aeruginosa (n = 49), Acinetobacter baumannii (n = 44) and Stenotrophomonas maltophilia (n = 10)., Results: The rates of categorical agreement (CA), essential agreement (EA) and bias were calculated to evaluate the performance of the UMIC® Cefiderocol, as compared with the reference method. Overall, the UMIC® Cefiderocol showed 90.8% EA (95% CI: 86.9%-93.7%) with a bias of -14.5% and a CA of 90.1% (95% CI: 86.1%-93.1%). For Enterobacterales, the UMIC® Cefiderocol showed 91.7% EA (95% CI: 86.7%-94.9%) with a bias of -25.0% and a CA of 87.8% (95% CI: 82.2%-91.8%). For non-fermenters, the UMIC® Cefiderocol showed 89.3% EA (95% CI: 81.9%-93.9%) (not significantly different from 90.0%, Student t-test) with a bias of -3.9% and a CA of 94.2% (95% CI: 87.7%-97.3%)., Conclusions: UMIC® Cefiderocol is a valid method for the determination of cefiderocol MICs even if higher than expected discrepancies were observed with NDM-producing Enterobacterales, which presented in most cases MIC values close to the breakpoint., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance., Methods: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation., Results: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94., Conclusions: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research., (© 2023. The Author(s).)

Due to the global spread of pan resistant organisms, colistin is actually considered as one of the last resort antibiotics against MDR and XDR bacterial infections. The emergence of colistin resistant strains has been observed worldwide in Gram-negative bacteria, such as Enterobacteriaceae and especially in K. pneumoniae, in association with increased morbidity and mortality. This landscape implies the exploration of novel assays able to target colistin resistant strains rapidly. In this study, we developed and evaluated a new MALDI-TOF MS assay in positive-ion mode that allows quantitative or qualitative discrimination between colistin susceptible (18) or resistant (32) K. pneumoniae strains in 3 h by using the "Autof MS 1000" mass spectrometer. The proposed assay, if integrated in the diagnostic workflow, may be of help for the antimicrobial stewardship and the control of the spread of K. pneumoniae colistin resistant isolates in hospital settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AL declared a past co-authorship with the authors GMR, VDP to the handling editor at the time of review., (Copyright © 2023 Foglietta, De Carolis, Mattana, Onori, Agosta, Niccolai, Di Pilato, Rossolini, Sanguinetti, Perno and Bernaschi.)

A nosocomial outbreak by cefiderocol (FDC)-resistant NDM-1-producing Klebsiella pneumoniae (NDM-Kp) occurred in a large tertiary care hospital from August 2021-June 2022 in Florence, Italy, an area where NDM-Kp strains have become endemic. Retrospective analysis of NDM-Kp from cases observed in January 2021-June 2022 revealed that 21/52 were FDC-resistant. The outbreak was mostly sustained by clonal expansion of a mutant with inactivated cirA siderophore receptor gene, which exhibited high-level resistance to FDC (MIC ≥ 32 mg/L) and spread independently of FDC exposure.

Background and Objectives: Patients with pediatric-onset multiple sclerosis (MS) can be especially vulnerable to cognitive impairment (CI) due to the onset of MS during a critical period for CNS development and maturation. The objective of this longitudinal study was to assess long-term cognitive functioning and socioprofessional attainment in the Italian pediatric MS cohort, previously assessed at baseline and 2 and 5 years., Methods: The 48 patients evaluated at the 5-year assessment were screened for inclusion. All participants were assessed with a cognitive test battery exploring 4 different cognitive abilities. Depression, fatigue, and socioprofessional attainment were also assessed. Mean cognitive z scores were calculated for the whole cohort, and their evolution over time was analyzed with an analysis of variance for repeated measurements test. Predictors of cognitive worsening or improvement were assessed with a linear mixed-model analysis., Results: Thirty-three participants were included (mean follow-up 12.8 ± 0.8 years). The global cognitive performance worsened at year 2 and improved at year 5, although the z score remained significantly lower than at baseline (-0.9 ± 1.2 vs -0.3 ± 0.9, p = 0.002). There was no significant variation between years 5 and 12 (-0.7 ± 1.1, p = 0.452). Higher IQ (>90) at baseline (effect 0.3, 95% CI 0.1-0.5, p = 0.017) and lower number of relapses in the 2 years before baseline (effect -0.1, 95% CI -0.1 to 0.1, p = 0.025) predicted better cognitive performances. Eighteen (54.5%) patients failed at least 2 tests compared with healthy controls and were defined as cognitively impaired. The presence of CI predicted worse socioprofessional attainment (β = 4.8, 95% CI 1.4-8.2, p = 0.008)., Discussion: The longitudinal cognitive trajectory in pediatric-onset MS has a heterogeneous course over time, with a decline in the first years followed by a partial recovery over the long term. However, at the last follow-up evaluation, the proportion of impaired patients was more than double compared with baseline, with a negative impact on the individual's socioprofessional attainment in adulthood. This study underscores how cognitive reserve may partially mitigate the negative effects of brain damage, highlighting the critical importance of intellectual enrichment early during the disease course., (© 2022 American Academy of Neurology.)

Background: Carbapenemase-producing Enterobacterales (CPE), particularly those producing metallo-β-lactamases, are among the most challenging antibiotic-resistant pathogens, causing outbreaks of difficult-to-treat nosocomial infections worldwide. Since November 2018, an outbreak of New Delhi metallo-β-lactamases-positive CPE (NDM-CPE) has emerged in Tuscany, Italy. In this study, we aimed to investigate the NDM-CPE associated with the outbreak and characterise the responsible Klebsiella pneumoniae clone., Methods: We used whole-genome sequencing and bioinformatic analysis to characterise NDM-CPE isolates that caused bloodstream infections in 53 patients at 11 hospitals in Tuscany and that were collected between Jan 1, 2018, and July 5, 2019 (ie, the early phase of the outbreak and preceding months). The CPE isolates characterised in this study were isolated and identified at the species level and as NDM producers by six diagnostic microbiology laboratories that serve the 11 hospitals. We used comparative genomic analysis, antimicrobial susceptibility testing, plasmid conjugal transfer assays, evaluation of virulence potential in the Galleria mellonella infection model, and serum bactericidal assays to further characterise the clone causing the outbreak., Findings: The outbreak was sustained by an ST147 K pneumoniae producing NDM-1, which had a complex resistome that mediated resistance to most antimicrobials (except cefiderocol, the aztreonam-avibactam combination, colistin, and fosfomycin). The clone belonged to a sublineage of probably recent evolution, occurred by the sequential acquisition of an integrative and conjugative element encoding the yersiniabactin siderophore, an FIB(pQil)-type multiresistance plasmid carrying bla NDM-1 , and a transferable chimeric plasmid, derived from virulence elements of hypervirulent K pneumoniae, carrying several resistance and virulence determinants. Infection of G mellonella larvae revealed a variable virulence potential. The behaviour in serum bactericidal assays was different from typical hypervirulent K pneumoniae strains, with variable grades of serum resistance apparently associated with mutations in specific chromosomal loci (csrD, pal, and ramR)., Interpretation: This description of a sublineage of ST147 K pneumoniae with a complex resistome and virulome that is capable of sustaining a large regional outbreak adds to existing research on the evolutionary trajectories within high-risk clones of K pneumoniae. Global surveillance programmes are warranted to track the dissemination of these lineages, and to prevent and control their spread., Funding: Italian Ministry of Health and Department of Experimental and Clinical Medicine, University of Florence., Competing Interests: Declaration of interests GMR reports grants, personal fees, and non-financial support from Accelerate Diagnostics, personal fees from Becton Dickinson, Zambon, Roche, Thermo Fisher, QPex, Qiagen, and Pfizer, grants and personal fees from bioMérieux, Cepheid, MSD, Shionogi, Beckman Coulter, Menarini, Angelini Pharma, and Nordic Pharma, grants from Seegene, Arrow, Symcel, Hain Lifescience, Meridian, SetLance, Qvella, Qlinea, Biomedical Service, Quidel, and DID, and personal fees and fees for bacterial strains from Venatorx, outside the submitted work. TG reports personal fees from Alifax, bioMérieux, Thermo Fisher Scientific, Seegene, Accelerate Diagnostics, and VenatorX, and grants from AstraZeneca, outside the submitted work. AA reports personal fees from Seegene, Menarini, Arrow Diagnostic, and Accelerate Diagnostic, and non-financial support from SymCel, outside the submitted work. IB reports non-financial support from Diesse Diagnostica Senese, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Health professionals caring for persons with multiple sclerosis (MS) are faced with increasingly complex working conditions that can undermine their job satisfaction and the quality of their healthcare services. The aim of this study was to delve into health professionals' job satisfaction by assessing the predictive role of happiness and meaning at work. Specifically, it was hypothesized that job meaning would moderate the relationship between job happiness and satisfaction., Methods: The study hypothesis was tested among 108 healthcare professionals (53 physicians and 55 nurses) working in eight MS centers in Italy. Participants were administered the Eudaimonic and Hedonic Happiness Investigation and the Job Satisfaction Questionnaire. Hierarchical regression analysis was performed to test the moderating role of job meaning between job happiness and satisfaction., Results: A significant interaction effect of job happiness and meaning on job satisfaction was identified for both physicians and nurses. When work was attributed low meaning, participants experiencing high job happiness were more satisfied with their work than those reporting low happiness; by contrast, when work was perceived as highly meaningful, participants' levels of job happiness did not significantly contribute to job satisfaction., Conclusions: Focusing on the interplay between job happiness and meaning, findings bring forward practical suggestions for the preservation and promotion of job satisfaction among health professionals working with MS patients. Particularly, they suggest the need to strengthen those job-related aspects that may enhance job meaning, thus providing health professionals with significant reasons to persevere in their work in the face of daily challenges., (© 2021. The Author(s).)

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism was shown to strongly affect BDNF function, but its role in modulating gray matter damage in multiple sclerosis (MS) patients is still not clear. Given BDNF relevance on the hippocampus, we aimed to explore BDNF Val66Met polymorphism effect on hippocampal subfield volumes and its role in cognitive functioning in MS patients. Using a 3T scanner, we obtained dual-echo and 3DT1-weighted sequences from 50 MS patients and 15 healthy controls (HC) consecutively enrolled. MS patients also underwent genotype analysis of BDNF, neurological and neuropsychological evaluation. Hippocampal subfields were segmented by using Freesurfer. The BDNF Val66Met polymorphism was found in 22 MS patients (44%). Compared to HC, MS patients had lower volume in: bilateral hippocampus-amygdala transition area (HATA); cornus ammonis (CA)1, granule cell layer of dentate gyrus (GCL-DG), CA4 and CA3 of the left hippocampal head; molecular layer (ML) of the left hippocampal body; presubiculum of right hippocampal body and right fimbria. Compared to BDNF Val66Val, Val66Met MS patients had higher volume in bilateral hippocampal tail; CA1, ML, CA3, CA4, and GCL-DG of left hippocampal head; CA1, ML, and CA3 of the left hippocampal body; left HATA and presubiculum of the right hippocampal head. In MS patients, higher lesion burden was associated with lower volume of presubiculum of right hippocampal body; lower volume of left hippocampal tail was associated with worse visuospatial memory performance; lower volume of left hippocampal head with worse performance in semantic fluency. Our findings suggest the BNDF Val66Met polymorphism may have a protective role in MS patients against both hippocampal atrophy and cognitive impairment. BDNF genotype might be a potential biomarker for predicting cognitive prognosis, and an interesting target to study for neuroprotective strategies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated., Methods: A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical)., Results: The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70)., Conclusions: The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score., (© 2021. The Author(s).)